B Y T TRNG I HC DC H NI NGUYN VN CHIN HIU CHNH M HNH GY SI TIT NIU I N VI VO V P DNG NH GI TC DNG CA CC DC LIU D, B , XU H V LM V KHA LUN TT NGHIP DC S H NI - 2014

B Y T TRNG I HC DC H NI NGUYN VN CHIN HIU CHNH M HNH GY SI TIT NIU I N VI VO V P DNG NH GI TC DNG CA CC DC LIU D, B , XU H V LM V KHA LUN TT NGHIP DC S Ngi hng dn: TS. Nguyn Thy Dng DS. Phm c Vnh Ni thc hin: B mn Dc lc H NI 2014 LI CM N Trong qu trnh thc hin ti, ti nhn c s gip rt qu bu v tntnhcaccthyc,gianhvbnb.Vthcslngunnglc, ngun ng vin v khch l ti trong sut qu trnh thc hin ti. Ti xin by t li cm n chn thnh v lng bit n su sc n:oTS. Nguyn Thy Dng v TS. Nguyn Hong Anh nhng ngi thy, ngi c ch bo v nh hng ti thc hin ti ny. oDS. Phmc Vnhngithytrctiphngdntntnh cho ti, gip ti hon thnh ti. Ti cng xin chn thnh cm n n: oCc thy c, anh ch k thut vin B mn Dc lc nhit tnh gip ti trong sut qu trnh lm thc nghim. oTS. Nguyn Qunh Chi, Ths. L Thanh Bnh v cc anh ch k thut vinBmnDcliu,bmnCngnghipDcvccanhchcnbVin Dc liu, vin Ha sinh bin Vin Hn lm Khoa hc v Cng ngh Vit Nam h tr ti trong thi gian thc hin ti. oS Khoa hc cng ngh tnh Hi Dng cp kinh ph thng qua ti Khoa hc cng ngh cp tnh giai on 2012 2013 ti thc hin ti.oBan gim hiu cng ton th cc thy c trng i hc Dc H Ni to iu kin cho ti hc tp v tch ly nhng kin thc b ch trong sut 5 nm hc va qua. Licuicng,tixincmnnnhngngithntronggianh,nhng ngi bn, anh em tn tnh gip , h tr v lun bn cnh ti trong sut thi gian hc tp v nghin cu. H Ni, thng 5 nm 2014 Sinh vin Nguyn Vn Chin MC LC LI CM N ............................................................................................................... DANH MC CC K HIU, CC CH VIT TT ................................................. DANH MC CC BNG ........................................................................................... DANH MC CC HNH ............................................................................................. T VN ............................................................................................................. 1 CHNG 1: TNG QUAN ....................................................................................... 2 1.1.Sinh l bnh ca si tit niu ......................................................................... 2 1.2.D phng v iu tr bnh l si tit niu ..................................................... 4 1.2.1.iu tr ngoi khoa ................................................................................. 4 1.2.2.iu tr ni khoa ..................................................................................... 4 1.2.3.D phng ti pht ................................................................................... 4 1.3.Mt s m hnh gy si tit niu in vivo ....................................................... 5 1.3.1.M hnh gy qu bo ha oxalat niu ..................................................... 5 1.3.2.M hnh gy si calci oxalat trn chut tng bi tit calci do di truyn . 7 1.3.3.S dng ch n thiu ht pyridoxin ................................................... 8 1.3.4.Cy si vo bng quang .......................................................................... 8 1.4.Vi nt v cc dc liu s dng trong nghin cu ...................................... 9 1.4.1. d ......................................................................................................... 9 1.4.2.B ..................................................................................................... 10 1.4.3.Xu h ................................................................................................... 12 1.4.4.Lm v .................................................................................................. 14 CHNG 2. I TNG, PHNG TIN V PHNG PHP NGHIN CU .......................................................................................................................... 16 2.1.Nguyn liu nghin cu ............................................................................... 16 2.2.Phng tin nghin cu ............................................................................... 16 2.2.1.ng vt th nghim ............................................................................. 16 2.2.2.Ha cht v thuc th ........................................................................... 16 2.2.3.Thit b v dng c ............................................................................... 17 2.3.Ni dung nghin cu ................................................................................... 17 2.4.Phng php nghin cu ............................................................................. 17 2.4.1.Gy si tit niu in vivo trn thc nghim v nh gi tc dng ca chng dng natri citrat ..................................................................................... 17 2.4.2.p dng m hnh gy si tit niu in vivo hiu chnh nh gi tc dng c ch hnh thnh si tit niu ca cc dc liu d, B , Xu h v Lm v. .............................................................................................................. 21 2.4.3.Phng php x l s liu .................................................................... 22 CHNG 3. KT QU NGHIN CU ................................................................. 23 3.1.Kt qu phng php gy si tit niu in vivo trn ng vt thc nghim ... 23 3.1.1.nh hng ca m hnh gy si tit niu in vivo n th trng chut ... 23 3.1.2.nh hng ca m hnh gy si tit niu in vivo n khi lng c th chut. .................................................................................................................. 23 3.1.3.nh hng ca m hnh gy si tit niu in vivo n mt s ch s huyt hc ca ng vt th nghim .............................................................................. 24 3.1.4.nh hng ca m hnh gy si tit niu in vivo n mt s ch s ha sinh mu ca ng vt thc nghim .................................................................. 25 3.1.5.nh hng ca m hnh gy si tit niu in vivo n th tch nc tiu ........................................................................................................................... 25 3.1.6.nh hng ca m hnh gy si tit niu in vivo n pH nc tiu ...... 26 3.1.7.Tinh th calci oxalat trong nc tiu khi s dng m hnh gy si tit niu in vivo ......................................................................................................... 27 3.1.8.S lng ng tinh th trong thn khi s dng m hnh gy si tit niu in vivo bng ethylen glycol 0,75%. .................................................................... 29 3.2.Kt qu ca phng php nh gi tc dng c ch to si ca cc dc liu d, B , Xu h v Lm v ............................................................................ 31 3.2.1.nh hng ca cc dc liu n th tch nc tiu ............................. 31 3.2.2.nh hng ca cc dc liu n pH nc tiu .................................... 31 3.2.3.nh hng ca cc dc liu n s lng tinh th calci oxalat trong nc tiu ............................................................................................................ 32 3.2.4.Tc dng c ch s lng ng tinh th calci oxalat trong thn trn m hnh gy si tit niu bng ethylen glycol 0,75% .............................................. 35 CHNG 4: BN LUN ........................................................................................ 39 4.1. Bn lun v vic hiu chnh m hnh gy si tit niu trn thc nghim bng EG 0,75%. ..................................................................................................... 39 4.1.1.V nhng thay i trong m hnh gy si tit niu in vivo .................... 39 4.1.2.V kt qu hiu chnh m hnh gy si tit niu in vivo bng EG 0,75% ........................................................................................................................... 41 4.2. Bn lun v tc dng ca cc dc liu ..................................................... 44 4.2.1.V tc dng ca dc liu d .............................................................. 44 4.2.2.V tc dng ca cc dc liu khc ....................................................... 45 KT LUN V XUT ...................................................................................... 47 DANH MC CC K HIU, CC CH VIT TT AC:Amoni clorid ALT:Alanin aminotransferase AST:Aspartat aminotransferase CaOx: Calci oxalat COD:Calci oxalat monohydrat COM: Calci oxalat dihydrat EG: Ethylen glycol DANH MC CC BNG Bng 2.1: Thang im phn nh s lng tinh th CaOx trung bnh ....................... 20 Bng 3.1: Mt s ch s huyt hc ca ng vt thc nghim ca 3 nhm nghin cu trong 4 tun th nghim ...................................................................................... 24 Bng 3.2: Mt s ch s ha sinh ca ng vt thc nghim ca 3 nhm nghin cu trong 4 tun th nghim ............................................................................................. 25 Bng 3.3: im nh gi v s lng tinh th calci oxalat trong nc tiu ............. 27 Bng 3.4: im nh gi v s lng ng thn c kt tp si .................................. 29 Bng 3.5: nh hng ca m hnh nghin cu n th tch nc tiu (ml) ............. 31 Bng 3.6: nh hng ca cc dc liu n s lng tinh th calci oxalat trong nc tiu .................................................................................................................... 33 Bng 3.7: im phn nh mc kt tp si ti thn .............................................. 35 DANH MC CC HNH Hnh 1.1: Cy D (Coix lachryma-jobi L. Poaceae). ............................................. 10 Hnh 1.2: L cy b (Ficus religiosa L.Moraceae). ............................................. 11 Hnh 1.3: Cy xu h (Mimosa pudica L.Mimosaceae). .......................................... 13 Hnh 1.4: L cy Lm v (Ficus Rumphii B. Moraceae). ......................................... 14 Hnh 2.1: Quy trnh gy si tit niu ......................................................................... 18 Hnh 2.2: Quy trnh th nghim nh gi tc dng ca cc dc liu trn m hnh gy si tit niu ......................................................................................................... 22 Hnh 3.1: Khi lng c th ca chut ca 3 nhm nghin cu trong 28 ngy th nghim ....................................................................................................................... 23 Hnh 3.2: nh hng ca m hnh nghin cu n th tch nc tiu ..................... 26 Hnh 3.3: nh hng ca m hnh nghin cu n pH nc tiu chut .................. 26 Hnh 3.4: Hnh nh tinh th calci oxalat trong nc tiu phng i x400 ........ 28 Hnh 3.5: Hnh nh vi th thn chut phng i x100 ...................................... 30 Hnh 3.6: Hnh nh vi th thn chut phng i x400 ...................................... 30 Hnh 3.7: nh hng ca tng loi dc liu n pH nc tiu chut .................... 32 Hnh 3.8: Hnh nh tinh th calci oxalat trong nc tiu ca 6 l chut phng i x400 ..................................................................................................................... 34 Hnh 3.9: Hnh nh vi th thn ca 6 l chut phng i x100 ........................ 36 Hnh 3.10: Hnh nh vi th thn ca 6 l chut phng i x400 ...................... 37 1 T VN Si tit niu ltnh trng si c hnh thnh trong ng titniu gytc nghnngtitniu.VitNamnmtrongvngvnhaisicathgii,tl mc si thnt 2 12 % ty theo tng vng[9], trong t l suy thn mn tin trin t bnh l si thn chim 31 44 % [13]. Phc iu tr c p dng cho tng trng hp da vo v tr, kch thc ca si, chc nng thn v sc khe ca bnhnhn.Trongkhiccthuchadccnnhiuhnchvhiuqu,iutr ngoi khoa mc d cho hiu qu cao nhng c kh nng gy tai bin v t l ti pht si cao.VitNamcngundcliuadng,phongphvinhiucythuc,bi thuc c s dng iu tr si tit niu. Qua mt s nghin cu sng lc in vitro,phthincccdcliuctcdngcchhnhthnhtinhthsi CaOx. Trong d, B , Xu h v Lm v l cc dc liu c tim nng [4], [6],[7],[12],[16].Ccdcliutrncphihptrongmtbithucdn gian c tc gi Nguyn Th Hi nh gi tc dng c ch si tit niu in vivo vchoktqubcu[5].Tuynhin,bithuccnhgitrnmhnh thc nghim tc gi Phm c Vnh trin khai ti b mn Dc lc, Trng i hc Dc H Ni vn cn mt s hn ch do s dng chng dng cha ph hp v c tnh ca tcnhn gy si trn ng vt thc nghim [15]. Vimongmun khc phc c nhng nhc im trn xy dng mt m hnh gy si tit niu n nh, ph hp cho php nh gi chnh xc tc dng ca cc dc liu d, B , Xu h v Lm v, chng ti thc hin ti: Hiu chnh m hnh gy si tit niu in vivo v p dng nh gi tc dng ca cc dc liu d, B , Xu h v Lm v vi hai mc tiu: 1.Hiu chnh m hnh gy si tit niu trn ng vt thc nghim bng ethylen glycol. 2.nh gi tc dng ca cc dc liu D, B , Xu h v Lm v trn m hnh gy si tit niu bng ethylen glycol hiu chnh. 2 CHNG 1: TNG QUAN 1.1.Sinh l bnh ca si tit niu Sititniultnhtrngbnhlthnggptrongccbnhlngtit niu.Mcdccpntrtlutrongccyvn,nhngqutrnhhnh thnhsititniuhinchachiubity.Sititniudonhiunguyn nhn v nhiu qu trnh phc tp gynn[13]. Hai thuyt chnh c a rahin naygiithchqutrnhhnhthnhsil:thuythttdo(freepartical)v thuyt ht c nh (fixed partical) [9]. - Thuyt ht t do cho rng: ht khi u c hnh thnh ngoi t bo (trong lng ng thn) do hin tng tng bi tit cc cht ha tan vo nc tiu ti mcquboha,gykttinhthnhcctinhth.Cctinhthtrongnctius dnh vo nhau to thnh nhn, cc nhn mi tip tc kt tp to thnh ht ln hn.Cchtsinytritheodngnctiuvbbyliccvtrhpca ngtitniu.Ticcvtrny,chngtiptckttpthmcctinhthvln dn ln to thnh si. -Thuythtcnhchorng:qutrnhhnhthnhsikhiubngs lng ng cc mui trong cc m k thn hoc trong cc t bo ng thn. Cc m v cc t bo ny b ph hy v lm bc l ra cc tinh th. Cc tinh th ny tr thnh nhn gn vimt v tr ng thn hocm thn. Cc nhn nyln dn ln do s kt tp lin tc cc tinh th, ri sau bong ra theo dng nc tiu. Cc ht si ny b by li cc v tr hp ng tit niu v tip tc ln ln tr thnh si. Tuy mi thuyt nhn mnh n v tr v c ch khi u ca qu trnh to si khc nhau, nhng qu trnh hnh thnh si tit niu c th tm li thnh 3 giai on chnh:Giai on 1: Qu trnh qu bo ha cc cht ha tan trong nc tiu Nctiutrnn qu bo ha khi nng cc ion hatan ca mt chttrong nc tiu vt qu gii hn ha tan ca cht . S qu bo ha cc cht ha tan trong nc tiu l ng lc cho s kt tinh ca tinh th. Vic tng bi tit mt s cht ha tan nh calci, oxalat, phosphat trong nc tiu gy qubo ha v cc 3 chthatannyskttinhlithnhcctinhthtrongnctiu[9],[33],[53]. Trongnctiubnhthngcccchtcchnhcitrat,magnesicthlm tng mc bo ha ca cc mui calci trong nc tiu [9], [17]. Khi cc cht ny khng hot ng hoc nng cc cht ny gim xung trong nc tiu s dn n s bo ha cc cht ha tan trong nc tiu v hnh thnh nn cc tinh th. Giai on 2: Qu trnh hnh thnh cc ht si tit niu Stonhn:Qutrnhnybtukhicctinhthmuikthpvinhau trong nc tiu to thnh nhn. S kt tp tip tc din ra ngay c khi nng cc cht ha tan thp hn nng xy ra qu trnh kt tinh ban u [17]. Cc ht nhn c th hnh thnh trong ng thn, trn t bo hoc bn ngoi t bo [17], [53]. Nhn c hnhthnh trnmt bmt gi l nhn hn tp [17]. Tnthng t bong thncngthcyqutrnhkttinhvhnhthnhhtnhndotoranhng trung tm hnh thnh nn cc ht nhn hn tp ny [17]. Slnlncanhn:Htnhnlndnlndo2qutrnh:cciontdung dch gn trc tip vo ht nhn v s kt tp ca nhng tinh th hoc cc ht nhn t do trong nc tiu vi cc ht nhn hn tp [9], [17], [53]. Qu trnh ny b nh hng bi nhiu cht c trong nc tiu. S tn ti ca cht kt dnh sinh hc nh ccmucoidkhngchiu,ccmucoproteinchiu,vdngpolymerca mucoproteinTamm-Horsfall,ccchtktdnhnylmchmdichuyncacc tinh th v cc nhn con gy kt tp chng vo nhau v vo nhn hn tp [9], [17].Giai on 3: Qu trnh gn cc tinh th si vo m thnCchtngtcgiatbovtinhthsirtphctp,hinchac hiu bit y . Qu trnh gn ca cc ht c hnh thnh trc vo cc t bo biu m ng thn c th do tng tc vt l, trong , cc ht si trong nc tiu b by li ti cc v tr hp ng tit niu,gn v tip tc pht trin ln ln[9], [53].Qutrnhgncthcybimtsphntnhhyaluronan,nucleolin, annexin II, v osteopontin [53].4 1.2.D phng v iu tr bnh l si tit niu 1.2.1.iu tr ngoi khoa Vicchnhiutrngoikhoavphngphpngoikhoapdngph thuc vo v tr, kch thc ca si, tnh trng chc nng thn v th trng ca bnh nhn [9], [13], [37]. i vi nhng si c ng knh > 5mm kh lt qua niu qun v/hoc bt k du hiu no ca s tc nghn ng tit niu do si, nht l si gytcnghnlmginibthn2trlnthcnphicanthipngoikhoa [9].Mt s phng php ngoi khoa c th s dng l tn si ngoi c th, ni soi ly si, loi si bng laze, hoc tn si qua da..[9], [37], [52]. 1.2.2.iu tr ni khoa -Thuc tng si ra ngoi c th: cc nghin cu gn y cho thy thuc chn knh calci v thuc chn giao cm l nhng thuc c tim nng trong iu tr si tit niu. Trong , thuc chn knh calci c tc dng lm gin c trn, chng co tht niu qun. Mt s thuc gin c trn khc c s dng nh thuc chn giao cm, kch thch chn lc 1 [9], [37], [47]. Bn cnh , c th s dng mt s thuc c ngun gc dc liu nh nc n vi. Hiu qu ca nc n vi c chng minh trong mt s nghin cu in vitro v in vivo [9]. -Thucgimaucsdnglmgimcctriuchngcabnhnhn. Trong , cc thuc gim au chng vim khng steroid (NSAIDs) nh meloxicam, diclofenac.csdngllachnutaygimauchobnhnhn.Cc thucgimautrungngnhmorphin,codeincngcthcsdngkhi cc NSAIDs khng hiu qu [13], [67]. -Khngsinh:csdngkhicsistruvithocsititniukmtheo nhim khun [9], [67]. -Cc thuc iu tr bin chng (nu c) nh i mu, suy thn..[9], [13]. 1.2.3.D phng ti pht Ch n, ung nhngbnhnhnkhngcnguyccao,kimsotchnvlng nc ung hng ngy c th l d phng ti pht si tit niu [9], [37], [67].5 - Ung nhiu nc m bo th tch nc tiu 24 gi ti thiu l 2 lt. -Chnnhiurauvchtx,hnchprotein(0,8-1g/kg),mui ( 0,05). 3.1.3.nh hng ca m hnh gy si tit niu in vivo n mt s ch s huyt hc ca ng vt th nghim Nghin cu nh hng ca m hnh gy si thn bng ethylen glycol 0,75% lnccchshuythccangvtthcnghimbaogm:slnghngcu (RBC),nnghemoglobin(HGB),tlhematocrit(HCT),slngtiucu (PLT), s lng bch cu (WBC) ti thi im kt thc th nghim. Kt qu c trnh by bng 3.1 Bng 3.1: Mt s ch s huyt hc ca ng vt thc nghim ca 3 nhm nghin cu trong 4 tun th nghim Bnh thngEG 0,75%EG 0,75% + citrat n = 8n = 9n = 9 RBC (1013/L)6,62 0,377,08 0,487,05 0,25 WBC (109/L)8,1 0,59,1 0,98,2 0,6 PLT (109/L)492,80 37,56575,75 38,20495,62 26,60 HGB (g/dL)0,34 0,020,38 0,030,36 0,01 HCT (%)89,2 5,898,0 6,395,5 3,4 Nhn xt:Khngcskhcbitcnghathngkvccchshuyt hc (RBC, WBC, PLT, HGB, HCT) gia cc l nghin cu (p > 0,05).25 3.1.4.nhhng ca m hnh gy si tit niu in vivo n mt s ch s ha sinh mu ca ng vt thc nghim NghincunhhngcamhnhgysithnbngEG0,75%lnchc nnggan,chcnngthncachutthnghimthngquaccchsnngcc enzym ASAT, ALAT v nng creatinin (Cr) trong huyt thanh ti thi im kt thc th nghim. Kt qu c trnh by bng 3.2 Bng 3.2: Mt s ch s ha sinh ca ng vt thc nghim ca 3 nhm nghin cu trong 4 tun th nghim Bnh thngEG 0,75%EG 0,75% + citrat n = 8n = 9n = 9 ASAT (U/L)93,33 14,4082,62 5,0198,25 10,60 ALAT (U/L)44,83 4,6044,62 2,5045,50 4,20 Creatinin (mol/L)118,0 28,0102,0 11,0152,0 41,1 Nhn xt: Khng c s khc bit c ngha thng k v cc ch s ha sinh (ASAT, ALAT, Cr) gia cc l nghin cu (p > 0,05). 3.1.5.nh hng ca m hnh gy si tit niu in vivo n th tch nc tiu Xcnhthtchnctiu5gicatngl.Sosnhthtchnctiu5 gi ca cc l nghin cu thy nh hng ca m hnh nghin cu n th tch nc tiu ca chut th nghim. Kt qu c trnh by trong hnh 3.2. Nhn xt: Th tch nc tiu l dng EG 0,75% + natri citrat cao hn c ngha thng k so vi l dng EG 0,75%. KhngcskhcbitvthtchnctiugialdngEG0,75%vl bnh thng (p > 0,05). 26 Hnh 3.2: nh hng ca m hnh nghin cu n th tch nc tiu bb p < 0,01 khi so snh vi l EG 0,75% 3.1.6.nh hng ca m hnh gy si thn in vivo n pH nc tiu Saukhixcnhthtchnctiu5gicachut,tinhnhopHnc tiu chut ca tng l.Kt qu c th hin hnh 3.3 Hnh 3.3: nh hng ca m hnh nghin cu n pH nc tiu chut 3.073.11 8.31bb 024681012Bnh thng (n=8)EG 0,75%(n=9) EG 0,75% + citrat(n=9)Th tch nc tiu 5 gi (ml) 8,46 8,23 8,75 012345678910Bnh thng (n=8)EG 0,75% (n=9) EG 0,75% + citrat (n=9)pH nc tiu 27 Nhn xt: pH nc tiu gia cc l nghin cu khng c s khc nhau c ngha thng k (p > 0,05). 3.1.7.Tinh th calci oxalat trong nc tiu khi s dng m hnh gy si tit niu in vivo V s lng tinh th niu: Quansttinhthniudiknhhinviquanghcvnhgitheothang im, kt qu c th hin bng 3.3. Bng 3.3: im nh gi v s lng tinh th calci oxalat trong nc tiu Ln im phn nh tinh th calci oxalat (t phn v) Bnh thng80 (0 0)L EG 0,75%93 (3 3)aa L EG 0,75% + citrat90 (0 0)bb aa p < 0,01 khi so snh vi l bnh thng bb p < 0,01 khi so snh vi l EG 0,75% Nhn xt: S lng tinh th calci oxalat trong nc tiu l EG 0,75% cao hn c ngha thng k so vi l bnh thng. lEG0,75%+citrat,slngtinhthcalcioxalattrongnctiuthp hn c ngha thng k so vi l EG 0,75%. V hnh nh tinh th niu: Hnhnhtinhthcalcioxalattrongnctiucthhintronghnh3.4 di y. Nhn xt: Tinh th calci oxalat ch c quan st thy l EG 0,75%, gm ch yu l tinh th COM. Trong khi , khng c mt tinh th calci oxalat cc l bnhthngvlEG0,75%+citrat.lbnhthng,chquanstthynhng tinh th struvit. 28 L bnh thng L EG 0,75% L EG 0,75% + citrat Hnh 3.4: Hnh nh tinh th calci oxalat trong nc tiu phng i x400 COM Struvit Struvit COM COM 29 3.1.8.S lngng tinh th trong thn khi s dng m hnh gy si tit niu in vivo bng ethylen glycol 0,75%. V s lng ng thn lng ng tinh th calci oxalat: Soi tiu bn thn di knh hin vi quang hc phn cc xc nh s lng ng thn xut hin lng ng cc tinh th. Kt qu c trnh by trong bng 3.4: Bng 3.4: im nh gi v s lng ng thn c kt tp si L n im phn nh mc lng ngtinh th calci oxalat ti thn Bnh thng80,0 (0,0 0,0) L EG 0,75%910,0 (3,5 10,0)aa L EG 0,75% + citrat90,1 (0 0,1)bb aa p < 0,01 khi so snh vi l bnh thng bb p < 0,01 khi so snh vi l EG 0,75% Nhnxt:SkttptinhthcalcioxalattithnlgysibngEG 0,75% cao hn c ngha thng k so vi l bnh thng. l s dng EG 0,75% + citrat, s lng ng si ti thn thp hn l gy si bng EG 0,75% c ngha thng k. V hnh nh m bnh hc thn di knh hin vi quang hc phn cc: Hnh nh vi th thn ca cc chut i din cho tng l c trnh by trong cc hnh 3.5, 3.6 Nhn xt: Trn hnh nh vi th thn cho thy, l bnh thng, vi th thn bnhthng,khngthyctinhthcalcioxalatlngngtrongccngthn. Trong khi , l EG 0,75%, tinh th calci oxalat lng ng rt nhiu, t li thnh cc m ln, nm nhiu v tr khc nhau v ri rc trong thn t vng v thn n vng nh thn. l EG 0,75% + citrat hu nh khng c s lng ng tinh th calci oxalat cc ng thn. Trong mt vi tiu bn, ch c 1 hoc 2 ng thn c s lng ng tinh th calci oxalat thnh m nh. 30 A BC Hnh 3.5: Hnh nh vi th thn chut phng i x100 A BC Hnh 3.6: Hnh nh vi th thn chut phng i x400 A: Hnh nh vi th thn chut l bnh thngB: Hnh nh vi th thn chut l EG 0,75% C: Hnh nh vi th thn chut l EG 0,75% + citrat31 3.2.Kt qu ca phng php nh gi tc dng c ch to si ca cc dc liu d, B , Xu h v Lm v 3.2.1.nh hng ca cc dc liu n th tch nc tiu Xcnhthtchnctiu5gicatngl.Sosnhthtchnctiu5 gi ca cc l ung ch phm th vi l chng bnh v l chng dng nh gi nh hng ca tng dc liu n th tch nc tiu chut th nghim. Bng 3.5: nh hng ca cc dc liu n th tch nc tiu (ml) LLiu (g/kg)nTh tch nc tiu (ml) Chng bnh - 83,3 0,4 Chng dng2,598,4 0,4** d2,5283,2 0,5## B 2,5292,5 0,4## Xu h2,5293,9 0,3## Lm v2,5292,9 0,4## ** p < 0,01 so vi chng bnh ## p < 0,01 so vi l chng dng Nhn xt:Khisosnhvilchngbnh,thtchnctiulchng dng cao hn c ngha thng k. Trong khi , th tch nc tiu cc l ung caolngd,B,XuhvLmvkhngcskhcbitsovichng bnh. 3.2.2.nh hng ca cc dc liu n pH nc tiu Saukhixcnhthtchnctiu5gicachut,tinhnhopHnc tiu chut ca tng l.Kt qu c trnh by trong hnh 3.7. 32 Hnh 3.7: nh hng ca tng loi dc liu n pH nc tiu chut Nhn xt: pH nc tiu cc l thuc th v l chng dng khng c s khc bit ng k so vi l chng bnh (p > 0,05).3.2.3.nhhng caccdc liun s lng tinh th calci oxalat trong nc tiu Quansttinhthniudiknhhinviquanghc,nhgislngv kch thc cc tinh th CaOx (bao gm cc tinh th COM v COD). V s lng tinh th calci oxalat trong nc tiu:Sau khi m s lng tinh th CaOx bng knh hin vi quang hc phng i x400 v cho im theo bng 2.1.Kt qu c trnh by trong bng 3.6: 6,94 7,12 7,07 7,45 7,07 7,51 012345678Chng bnh (n=8) Chng dng (n=9) d (n=8) B (n=9)Xu h (n=9)Lm v (n=9) pH nc tiu 33 Bng 3.6: nh hng ca cc dc liu n s lng tinh th calci oxalat trong nc tiu LLiu (g/kg)n im nh gi s lng tinh th niu (t phn v) Chng bnh-83 (3 3) Chng dng2,590 (0 0)** d2,5283 (2 3)## B 2,5293 (3 3) ## Xu h2,5293 (3 3) ## Lm v2,5293 (3 3) ## ** p < 0,01 khi so snh vi chng bnh ## p < 0,01 khi so vi l chng dng Nhn xt:Slngtinhthcalcioxalattrongnctiulchngdng thp hn c ngha thng k so vi l chng bnh. cc l thuc th th khng c s khc bit v s lng tinh th CaOx trong nc tiu so vi l chng bnh. V hnh nh tinh th niu: Hnh nh tinh th calci oxalat ca cc l c trnh by trong cc hnh 3.8. Nhn xt: Hnh nh tinh th niu cho thy, tinh th calci oxalat c mt c cc l chng bnh, d, B , Xu h v Lm v. l chng bnh, cc tinh th c kch thc ln, s lng tinh th COM nhiu hn s lng tinh th COD. Trong khi , khi quan st l chng dng thy s lng tinh th calci oxalat l rt t, kch thcrtnhvchyutnlidngCOD,tlCOD/COMcxuhngtng ln. T l ny cng c xu hng tng ln l d v l B . 2 dc liu Xu hvLmv,kchthccctinhthln,tlCOD/COMcxuhnggim xung hoc gi nguyn.34 Chng bnh Chng dng d

B Xu h Lm v Hnh 3.8: Hnh nh tinh th calci oxalat trong nc tiu ca 6 l chut phng i x400 A: L chng bnhD: L B B: L chng dngE: L Xu h C: L dF: L Lm v COM COD COD COM COM COM COM COD COD COD COD COM 35 3.2.4.Tc dng c ch s lngng tinh th calci oxalat trong thn trn m hnh gy si tit niu bng ethylen glycol 0,75% V s lng ng thn lng ng tinh th calci oxalat: Sau khi xc nh s lng ng thn xut hin lng ng cc tinh th. Kt qu c trnh by trong bng 3.7: Bng 3.7: im phn nh mc kt tp si ti thn LLiu (g/kg)n im phn nh mc lng ng tinh th calci oxalat ti thn Chng bnh-88,0 (2,2 9,6) Chng dng2,590,4 (0,2 0,7)* d2,5280,2 (0,0 1,0) B 2,5294,0 (0,0 10,0) # Xu h2,5292,8 (1,0 10,0)# Lm v2,5295,5 (1,0 9,9) # * p < 0,05 khi so snh vi chng bnh # p < 0,05 so vi l chng dng Nhn xt: S lng ng thn c kt tp si l chng dng thp hn c ngha thng k so vi l chng bnh. S lng ng thn c kt tp si l d thp hn c ngha thng k so vi l chng bnh v khng c s khc bit ng k khi so vi l chng dng. Trongkhi,cclungcaolngB,XuhvLmvkhngcs khc bit so vi l chng bnh v s lng ng thn c kt tp si.V hnh nh m bnh hc thn di knh hin vi quang hc phn cc: Hnh nh vi th thn ca cc chut i din cho tng l c trnh by trong cc hnh 3.9, 3.10.36 Chng bnhChng dng d B Xu h Lm v Hnh 3.9: Hnh nh vi th thn ca 6 l chut phng i x100 37 Chng bnh Chng dng d B Xu hLm v Hnh 3.10: Hnh nh vi th thn ca 6 l chut phng i x400 38 Nhn xt: Trn hnh nh vi th thn, tinh th CaOx l chng bnh lng ng rt nhiu, kt t li thnh cc m si ln, nm ri rc trong thn. l chng dng v d hu nh khng c tinh th lng ng cc ng thn.Trong khi , cc l ung cao lng B , Xu h v Lm v, cc tinh th lng ng ti nhiu v tr khc nhau trong thn, cc m si kt tp li thnh cc m ln nh v nm ri rc trong thn. 39 CHNG 4: BN LUN 4.1. Bn lun v vic hiu chnh m hnh gy si tit niu trn thc nghim bng EG 0,75%. 4.1.1.V nhng thay i trong m hnh gy si tit niu in vivo Trn th gii c rt nhiu nghin cu v m hnh gy si tit niu thc nghim, tuy nhin, cha c s thng nht gia cc tc gi. Cc m hnh gy si tit niu rt khc nhau c v ha cht, liu lng, thi gian. S khc nhau ny c th do ch n ung, iu kin nui dng hoc mc ch nghin cu. Vit Nam, cho n nay, mi c mt ti: Trin khai m hnhgy si tit niu trn ng vt th nghim ca tc gi Phm c Vnh v m hnh gy si tit niu thc nghim v thu c kt qu bc u. Tuy nhin, m hnh gy si tc gi Phm c Vnh trin khai vn cn mt s hn ch [15].V ha cht gy si: Mc d vic b sung AC lm tng kt tp si trong thn, ng thi, AC lm gim pH nc tiu; pH nc tiu gim cng l yu t nguy c gy si tit niu. Tuy nhin, do mt s hn ch khi s dng AC kt hp trong nghin cu trin khai nn chng ti loi b AC trong thnh phn ha cht gy si. Trcht,ctnhcamhnhEGkthpamoniclorid(AC)thhinrtrn ngvtthnghimtrongkhikhngcbiuhinbtthngnocghinhnkhis dng m hnh EG n c. c tnh ca m hnh EG + AC th hin th trng chut v t l chut cht trong qu trnh th nghim. Th trng chut b nh hng ln nh chut chm ln hn, chut c du hiu gim n, ung. T l chut cht trong qu trnh nghin cu l 33% (3/9 chut cht trong qu trnh th nghim). Th trng chut xu i cng nh t l chut cht cao cng c ghi nhn trong nghin cu ca Fan v cc cng s v m hnh gy si tit niu trn thc nghim khi nng AC > 0,5% [31]. Hn na, c tnh camhnhtrinkhaicthdoACckhnnggysuyngthn.Hnchkhcca vic b sung AC l kt qu chng dng natri citrat khng th hin c tc dng. Vic s dng chng dng natri citrat nh gi tc dng trn m hnh EG kt hp vi AC 40 chacchngminhvkhngnh.Mtchtcgilchngdngchomtm hnh khi n l mt thuc tn dc, c c ch tc dng v hiu qu r rng, c chng minh hoc c thanhn rng ri [34], [36]. Citrat cmt stc gis dng lm chng dng trong cc nghin cu nh gi tc dng c ch hnh thnh si thn ca mt s dc liu trn m hnh EG n c [45], [65]. Nhng cha c tc gi no s dng citrat lm chng dng nh gi tc dng trn m hnh EG + AC. Hn na, s bi tit ca citrat ph thuc vo cn bng acid bas trong nc tiu. Vic s dng AC lm gim pH nc tiu, iu ny c th nh hng n tc dng ca citrat: pH nc tiu gim, dn n s ti hp thu citrat trong ng thn tng, lm gim nng citrat trong nc tiu, do lm gim tc dng ca citrat [31]. Mt khc, AC c v ng lm cho chut c th gim ung nc, lm gim lng EG c a vo c th chut, do nh hng n s qu bo ha oxalat trong nc tiu chut v nh hng n qu trnh hnh thnh si tit niu. Nh vy, nghin cu ca chng ti ch s dng EGn c gy si trn chut cng trng.V nng cht gy si: Trong hu ht cc nghin cu c cng b cng nh trong nghin cu trin khai ca tc gi Phm cVnh, nng EG c s dng dao ng trong khong t 0,5% n1%.Ktquthuccngrtdaong,tlchutcsit0%n71,4%[27], [40], [43]. Nghin cu cho thy t l si cao nht l 71,4% s dng EG 0,75% [43]. Vy nn, chng ti la chn nng EG 0,75%. V ng vt th nghim: Trongnghincutrinkhai,tcgisdngcchutcngtrnggingcv ging ci. iu ny c nh hng n t l chut c si. Cc nghin cu cho thy, t l chut c si ging c cao hn so vi ging ci [40]. Tc l, vic gy si tit niu bng EGphthucvogingc/ci.Khichsdngchutcngtrnggingcthtl chutcsistngln,do,nghincucachngtichsdngchutcngtrng ging c gy si. 41 4.1.2.V kt qu hiu chnh m hnh gy si tit niu in vivo bng EG 0,75% Chng ti tin hnh th nghim gy si tit niu in vivo bng EG 0,75%, s dng natricitratlmchngdng.Chngtitheodi,quanstvnhgimhnhtrn cc thng s: khi lng c th v th trng chut, cc ch s ha sinh v cng thc mu, th tch nc tiu, pH nc tiu, s lng v kch thc tinh th CaOx trong nc tiu v mc lng ng si trong thn (m bnh hc thn). -V khi lng v th trng chut Kt qu nghin cu cho thy rng m hnh gy si tit niu trn thc nghim bng EG 0,75% khng nh hng n khi lng chut cng nh th trng chut. Tt c chut ukhngghinhncduhiubtthngno.Khngcskhcbitnotng khilngcthchutgiacclnghincu.iunychothymhnhEG0,75% khng c nh hng no trn th trng cng nh s pht trin ca ng vt th nghim. -V cc ch s ha sinh v cng thc mu. nhginhhngcamhnhlnchcnngganvchcnngthnca chut, chng ti nh lng mt s thng s cng thc mu nh RBC, HCT, Hb, PLT, WBCvmtsthngshasinhmunhnngcreatinin,ASAT,ALAT.Ktqu cho thy khng c s khc bit gia cc l nghin cu. Vic s dng EG 0,75% qua nc ung hng ngy ca chut v vic s dng natri citrat 2,5g/kg chut khng lm thay i ng k cc thng s ny trong vng 28 ngy th nghim. M hnh gy si tit niu trn thcnghimbngEG0,75%nckhngnhhngnchcnnggan,chcnng thn ca ng vt th nghim. -V th tch v pH nc tiu Th tch nc tiuthu c l EG 0,75%khng c s khc bitso vi l bnh thng.ccnghincukhc,likhngcsngnhtvskhcbitvthtch nc tiu l ung EG 0,75% trong 28 ngy so vi l bnh thng [51], [58]. Tuy nhin, vic s dng natri citrat 2,5g/kg li lm tng th tch nc tiu ln ng k so vi l EG 0,75%. Trong mt nghin cu khc, vic s dng citrat lm tng khng ng k th tch nctiuhocthmchlmgimthtchnctiusovilEG0,75%[45],[65].S 42 khc nhau nyc thdo iu kin lymunc tiu ph thuc vo:thi gian lymu, nhit , m ca mi trng th nghim, iu kin chm sc ng vt th nghim trong thi gian ly mu (c sau mi 2 gi, chng ti cho chut ung nc hoc EG 0,75% vi th tch 1ml/100g). Trongnghincuny,chngtighinhncpHnctiukhngcskhc nhau gia cc l nghin cu. Tuy nhin, nghin cu tc dng ca Rosa canina do Tayefi-Nasrabadivcccngsthchin,ktquchothypHlEG+citratcaohnc ngha thng k so vi l gy si bng EG [65]. S khc nhau ny c th l do s khc bit v ch n ca ng vt nghin cu. -V s lng v kch thc tinh th CaOx trong nc tiu V s lng tinh th CaOx trong nc tiu, kt qu cho thy s lng tinh th l EG 0,75% cao hn ng k so vi l bnh thng, trong khi , l EG 0,75% + citrat thp hn ng k so vi l EG 0,75%. L 0,75% + citrat gn nh khng quan st c tinh th no. iu ny c th do citrat vi liu 2,5g/kg to ra gii hn bo ha mui CaOx ln hnngngnngoxalatmctorabngEG0,75%,domkhngcskt tinh thnh cc tinh th CaOx v cng khng quan st c s c mt ca cc tinh th ny trong nc tiu [26], [72]. -V mc lng ng si trong thn Sau 28 ngy gy si tit niu thc nghim bng EG 0,75%, mc lng ng si trong thn l EG0,75% khc bit rrt so vil bnh thng.Kt qu ny cngph hp vi nhiu nghin cu khc trn th gii [48], [51], [58], [66]. Mc d, trong mt s nghincu,vicsdngmhnhEG0,75%nckhnggycsitrnthc nghim [31], [46]. S khc bit ny do rt nhiu yu t nh ch n ung, iu kin thi tit, tnh c th trong qun th nghin cu. Trong nghin cu ny, chng ti cng nhn thy rng: vng nh thn c s kt tp si nhiu hn v thnh cc m ln trong khi vng ty v vng v th si kt tp li t hn v ri rc. y cng l bng chng mt ln nachothyvicgysititniuinvivobngmhnhEGncgyquboha 43 oxalat trong nc tiu cho qu trnh hnh thnh si thn trn chut ging nh qu trnh ngi.V tc dng ca chng dng citrat, kt qu nghin cu cng cho thy tc dng c ch hnh thnh si tit niu in vivo ca natri citrat 2,5g/kg. Cc nghin cu trc y cng cho thy tc dng tng t ca citrat trn m hnh s dng EG n c [45], [65]. Kt qu nghin cu ca chng ti cng cho t l chut c si t 88,9% (1/9 chut khngcsi).TrongkhiccnghincukhctrnthgiisdngEGnccc nng khc nhau cho t l chut c si kh dao ng. Tuy nhin khng c nghin cu nochotlchutcsicaohn80%.Trong,LeevcngssdngEG0,5% trong vng 4 tun cho t l chut c si l 71,4% [43]; nghin cu ca Khan cho thy t l chut c si l 16,6% khi s dng EG 0,5% v 50% khi s dng EG 0,75% trong vng 24 ngy [40]; nghin cu trin khai ca tc gi Phm c Vnh khi s dng EG 1% cho tlchutcsil60%;trongkhisdngEG0,8%trong24ngy,nhmnghincu ca Boeve khng tm thy s lng ng si trong thn [27]. Khitrinkhaimhnhgysihiuchnhnhgitcdngcaccdc liu d, B , Xu h v Lm v, chng ti nhn thy l chng bnh, t l chut c si l 87,5% (7/8 s chut c si). Kt qu khng c s khc bit nhiu so vi nghin cu hiu chnh (t l chut c si l 88,9%). Trong khi ,chng dng natri citrat vi liu 2,5g/kg tip tc cho thy tc dng gim ng k mc lng ngsi trong thn,gim ngkslngtinhthCaOxbititquanctiucngnhlmtngthtchnc tiu 5h. Nh vy, m hnh gy si tit niu in vivo bng EG 0,75%n nh v ph hp cho php nh gi tc dng ca cc dc liu nghin cu. Tmli,vichiuchnhmhnhgysititniuinvivotrnchutbngEG 0,75% khc phc c cc hn ch ca m hnh EG + AC tc gi Phm c Vnh trin khai. ng thi, da trn cc tiu ch ca mt m hnh gy si tit niu thc nghim tt bao gm: 1) Cc ng vt th nghim phi gyc si tit niu v c kh nng lp li. 2) Nhng thay i bnh l ng tit niu ch do si gy ra, khng phi do c tnh ca ha cht gy si. 3) Cc triu chng c kim sot bng mt thuc c s dng 44 c hiu qu trn ngi [71]. M hnh gy si tit niu in vivo chng ti hiu chnh p ng c cc tiu ch c bn trn.4.2. Bn lun v tc dng ca cc dc liu Trong nghin cu ny, chng ti chit cc dc liu bng phng php ngm lnh vidungmilcn70o.Liuccdcliucngoisuytnghincucatcgi Nguyn Th Hi c s dng bi thuc gm 3 dc liu d, B v Xu h, kt qu bi thucvimcliuthpnht2,52g/kgbcuctcdngcchhnhthnhsitit niuinvivo[5].Ty,chngtipdngmcliuny(2,52g/kg)chomidcliu trong nghin cu. 4.2.1.V tc dng ca dc liu d Kt qu m bnh hc cho thy, d vi liu 2,52g/kg c tc dng lm gim ng kmclngngsitithn.Tcdngnycadkhngkhcbitsovinatri citrat 2,5g/kg. Nh vy, hiu qu trong vic c ch s hnh thnh si tit niu in vivo ca d 2,52g/kg tng t nh natri citrat 2,5g/kg. Cc kt qu khc cho thy: d khng lm nh hng n th tch nc tiu, pH nc tiu trn chut c gy si bng EG 0,75% trong 28 ngy. Mc d, d, mt dc liumtheoYhcctruyn,ctcdnglitiu.Tuynhin,tcdngnylcad nhn.Nghincucachngtisdngdchchitthndtrnchutgysitit niu bng EG 0,75% khng ghi nhn c tc dng li tiu. Kt qu s lng tinh th CaOx trong nc tiu cho thy, d khng lm gim s lngtinhthCaOxbititquanctiu.Nhvy,dkhngctcdnglmtng gii hn bo ha ca cc mui ha tan trong nc tiu khi ng vt s dng EG 0,75%. Trn hnh nh tinh th niu, qua quan st v hnh dng v kch thc cc tinh th CaOx, chngtithyrng,lchngbnh,cctinhthckchthcln,slngtinhth COM nhiu hn s lng tinh th COD. l d, kch thc tinh th CaOx nh hn so vi tinh th quan st c l chng bnh, t l COD/COM tng rt cao. T l ny thng nht vi nghin cu in vitro trc v t l COD/COM.45 Trong nghin cu catc gi Th Yn thc hin ti Trng i hc Dc H Ni nhm nh gi tc dng in vitro trn si tit niu ca d v s b nghin cu thnh phnctcdngchothy,acidp-coumaricphnlpctphnonethylacetatt thndnng0,1mg/mlv1,0mg/mluctcdngcchshnhthnhsi CaOx(mnhhnccitrat2,58mg/ml).Nghincukhcchothy,acidnyctcdng chng oxy ha [64] mt c ch c ch to si. Do , chng ti ngh n tc dng c chhnhthnhsititniutrninvivocadcvaitrcaacidp-coumaric.Tuy nhin, cn c nhng nghin cu tip theo khng nh vai tr c ch hnh thnh si ca acid p-coumaric trn ng vt thc nghim.C rt nhiu c ch c ch s hnh thnh si tit niu: li niu, c ch s kt tinh, duytrcnbngyutcchvthcytotinhth,cithinchcnngthn,iu chnh chuyn ha oxalat, chng oxy ha, c ch phospholipase, chng khun v tc dng gim au chng vim [38], [50]. C gi thuyt cho rng: d lm tng chuyn dng tinh th CaOx t dng COM kh o thi v dgn vo cc t bo thnh dng COD d o thihn.Do,lmgimsgncacctinhthlntbo,skttcctinhthvi nhau, v lm tng s o thi tinh th CaOx ra khi ng tit niu [5]. Tuy nhin, khi s dngBcngchoxuhngchuyndngtinhthtdngCOMsangdngCOD, nhng khng c ch c qu trnh hnh thnh si. Mt khc, acid p-coumaric chit xut t thn d d c tc dng c ch hnh thnh tinh th CaOx in vitro vi cc tinh th tn ti ch yu di dng COM. Chng ti khng thy mi tng quan gia tc dng chuyn dng tinh th v qu trnh hnh thnh si titniu. Do vy, cn c nhng nghin cu c th v chnh xc hn nh gi c ch trn.4.2.2.V tc dng ca cc dc liu cn li Kt qu nghin cu cho thy, B , Xu h v Lm v khng c tc dng c ch hnh thnh si tit niu in vivo.CbadcliutrncngkhngnhhngnthtchvpHnctiutrn chut c gy si bng EG 0,75% trong 28 ngy. Mc d, c nghin cu cho thy tc dng li tiu ca Xu h [69]. Tuy nhin, nghin cu ny s dng Xu h trn chut bnh 46 thng trong khi nghin cu ca chng ti s dng trn chut c gy si bng EG 0,75%. Mt khc, liu Xu h c tc dng li tiu l 100 mg/kg v 200 mg/kg v khng c tc dng liu cao hn. Trong khi nghin cu ca chng ti s dng Xu h vi liu 2,52g/kgchut,liucaohnnhiusoviliugylitiughinhnctrongnghin cu trn [69]. QuaquanstvhnhdngvkchthccctinhthCaOxbititranctiu, chngtithyrng,c3dcliuuchothykchthccctinhthln,tl COD/COMgim i so vi l chng bnh. Kt qu ny khng tng ng vi nhng ghi nhn in vitro trc , Xu h v Lm v c tc dng c ch hnh thnh tinh th CaOx v lmtngtlCOD/COM[4],[6][7],[12].cbitXuhctcdngtngchuyn dng t COM sang COD rt mnh vi kch thc tinh th nh [12]. Vi B , kch thc tinh th CaOx nh hn so vi l chng bnh, v t l COD/COM tngln. Kt qu nythngnhtvinghincuinvitrotrcvtlCOD/COM,nhnglikhngthngnhtv ktqu s lngtinhth CaOx [4],[7],[16], [12]. Nh vy, cc kt qu in vitro ca B , Xu h v Lm v khng c th hin trn in vivo. S khng thng nht gia nghin cu in vitro v nghin cu in vivo l iu dhiu.Crtnhiunguynnhnkhcnhaudnnktqutrnnghincuinvitro khng c th hin trn nghin cu in vivo. Nguyn nhn chnhdo qu trnh ha tan ca cc cht trong dch chit h tiu ha ca chut, qu trnh dc ng hc (qu trnh hp thu, phn b, chuyn ha, thi tr) ca cc cht c tc dng trong dch chit lm cho hot cht b bin i trong c th thnh cht khc khng c hot tnh hoc lm gim nng hot cht thn, t lm mt tc dng ca cc hot cht . Ngoi ra, c th k n thnh phn nc tiu in vitro khc so vi nc tiu in vivo nh s khc nhau v pH nc tiu lm thay i tan ca cc hot cht c trong dc liu, s khc nhau v cc chtctrongnctiugytngtcvicchotchtctcdngtrongccdc liu... S khc nhau gia liu s dng trn in vitro v in vivo, liu s dng trn in vivo l 2,52 g/kg trong khi nghin cu in vitro s dng cao lng 1/4 (25%). 47 KT LUN V XUT I.Kt lun Sau mt thi gian thc hin ti: Hiu chnh m hnh gy si tit niu in vivo bng ethylene glycol v p dng nhgitcdng caccdc liud,B , Xu h v Lm v, chng ti rt ra mt s kt lun sau: 1.hiuchnhcmhnhgysititniuinvivotrnchutbngEG 0,75%,xydngcmhnhgysinnh,ngtincyvkhcphc c cc hn ch trong nghin cu ca tc gi Phm c Vnh: -Gy c si thn cho ng vt th nghim trong vng 28 ngy v n nh. Cho t l chut c si cao (88,9%). -Khngcbiuhinctnh:thtrngchutbnhthngvkhngcchut cht trong qu trnh th nghim; chc nng gan, thn bnh thng. -Chng dng citrat 2,5g/kg th hin tc dng r rt trn m hnh hiu chnh. 2.nh gi c tc dng ca cc dc liu d, B , Lm v v Xu h (liu 2,52g/kg chut) trn m hnh gy si tit niu thc nghim: - d mc liu 2,52g/kg c tc dng c ch hnh thnh si tit niu in vivo. -Cc dc liu B , Lm v v Xu h mc liu 2,52g/kg khng c tc dng c ch hnh thnh si tit niu in vivo. II. xut Tip tc nghin cu su hn v dc l ca d pht trin d tr thnh dc liu tim nng trong d phng ti pht si tit niu.-nh gi c tnh, thm d c ch tc dng, thm d liu c tc dng ti u v kh nng kt hp vi cc dc liu khc trong kh nng d phng v iu tr si tit niu. -Phn lp v nh gi tc dng ca acid p-coumaric trong thn d trn m hnh gy si tit niu thc nghim. -Vimhnhhiuchnhc,tiptcpdngnhgitcdngcacc dc liu tim nng trong d phng v iu tr si tit niu. 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