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KARYA TULIS AKHIR
PENGARUH PAPARAN BENZENA PERINHALASI TERHADAP
EVALUASI HAPUSAN DARAH TIKUS PUTIH JANTAN (Rattus
norvegicus) STRAIN WISTAR
Oleh:
Wahyu Estu Septyah Margowati
201610330311080
FAKULTAS KEDOKTERAN
UNIVERSITAS MUHAMMADIYAH MALANG
2020
ii
HASIL PENELITIAN
PENGARUH PAPARAN BENZENA PERINHALASI TERHADAP
EVALUASI HAPUSAN DARAH TIKUS PUTIH JANTAN (Rattus
norvegicus) STRAIN WISTAR
KARYA TULIS AKHIR
Diajukan kepada
Universitas Muhammadiyah Malang untuk memenuhi
salah satu persyaratan dalam menyelesaikan
Program Sarjana Fakultas Kedokteran
Oleh:
Wahyu Estu Septyah Margowati
201610330311080
FAKULTAS KEDOKTERAN
UNIVERSITAS MUHAMMADIYAH MALANG
2020
iii
iv
v
vi
KATA PENGANTAR
Assalamu’alaikum Warahmatullahi Wabarakatuh
Puji syukur kehadirat Allah SWT karena atas rahmat dan hidayah-Nya,
penulisan tugas akhir ini dapat diselesaikan dengan baik dan tepat waktu. Shalawat
serta salam selalu tercurahkan kepada Rasulullah Muhammad SAW, keluarga, para
sahabat, dan pengikut beliau yang telah membawa duni ini dari zaman kegelapan
emunju zaman yang terang benderang.
Penelitian tugas akhir ini berjudul “Pengaruh Paparan Benzena Perinhalasi
Terhadap Evaluasi Hapusan Darah Tikus Putih Jantan (Rattus norvergicus) Strain
Wistar”. Tugas akhir ini diajukan untuk memenuhi persyaratan Pendidikan Sarjana
Fakultas Kedokteran Universitas Muhammadiyah Malang.
Penulis menyadari tugas akhir ini masih jauh dari kata sempurna, oleh
karena itu, penulis sangat mengharapkan saran dan masukan yang membangun.
Semoga karya tulis ini dapat menambah wawasan keilmuan dan bermanfaat bagi
semua pihak.
Wassalamu’alaikum Warahmatullahi Wabarakatuh
Malang, 14 Juni 2020
Penulis
xii
DAFTAR ISI
HALAMAN JUDUL ............................................................................................ i
HALAMAN PERSYARATAN GELAR .............................................................. ii
LEMBAR PENGESAHAN ................................................................................. iii
SURAT PERNYATAAN ORISINILITAS .......................................................... iv
LEMBAR PENGUJIAN ...................................................................................... v
KATA PENGANTAR ........................................................................................ vi
UCAPAN TERIMA KASIH .............................................................................. vii
ABSTRAK .......................................................................................................... x
ABSTRACT ......................................................................................................... xi
DAFTAR ISI ..................................................................................................... xii
DAFTAR TABEL ............................................................................................. xv
DAFTAR GAMBAR ........................................................................................ xvi
DAFTAR SINGKATAN ................................................................................. xvii
DAFTAR LAMPIRAN ................................................................................... xviii
BAB I PENDAHULUAN .................................................................................... 1
1.1. Latar Belakang ...................................................................................... 1
1.2. Rumusan Masalah ................................................................................. 3
1.3. Tujuan Penelitian ................................................................................... 3
1.3.1 Tujuan Umum ............................................................................... 3
1.3.2 Tujuan Khusus............................................................................... 3
1.4. Manfaat Penelitian.................................................................................. 3
1.4.1 Manfaat Akademik ........................................................................ 3
1.4.2 Manfaat Masyarakat ...................................................................... 4
BAB II TINJAUAN PUSTAKA .......................................................................... 5
2.1. Benzena ................................................................................................. 5
2.1.1. Benzena Secara Umum ................................................................. 5
2.1.2. Sifat Fisika dan Kimia Benzena .................................................... 6
2.1.3 Sumber Benzena di Lingkungan .................................................... 6
2.1.4 Toksikokinetika Benzena dalam Tubuh Manusia .......................... 8
xiii
2.1.5 Toksisitas Benzena ...................................................................... 10
2.1.6 Mekanisme Hematotoksisitas Benzena ........................................ 12
2.2. Proses Pembentukan Sel Darah (Hematopoiesis) .................................. 13
2.2.1 Sel Darah Merah (Eritrosit) ......................................................... 15
2.2.2 Sel Darah Putih (Leukosit) .......................................................... 18
2.2.3 Trombosit .................................................................................... 20
2.3. Anemia Aplastik .................................................................................. 21
2.3.1 Definisi Anemia Aplastik ........................................................... 21
2.3.2 Etiologi Anemia Aplastik ........................................................... 21
2.3.3 Patofisiologi Anemia Aplasstik ................................................... 22
2.3.4 Gejala Klinis Anemia Aplastik ................................................... 23
2.3.5 Kriteria Diagnosis Anemia Aplastik ............................................ 24
2.4. Evaluasi Hapusan Darah Tepi ............................................................... 25
2.4.1 Definisi........................................................................................ 25
2.4.2 Indikasi Dilakukan Evaluasi Hapusan Darah Tepi ....................... 26
2.5. Tikus .................................................................................................... 26
2.6. Hematopoiesis Tikus ............................................................................ 27
2.6.1 Eritrosit ....................................................................................... 28
2.6.2 Leukosit....................................................................................... 28
2.6.3 Trombosit .................................................................................... 28
BAB III KERANGKA KONSEP DAN HIPOTESIS.......................................... 29
3.1. Kerangka Konsep ................................................................................. 29
3.2. Hipotesis .............................................................................................. 30
BAB IV METODE PENELITIAN ..................................................................... 31
4.1. Jenis Penelitian ..................................................................................... 31
4.2. Tempat dan Waktu Penelitian ............................................................... 31
4.3. Populasi dan Sampel ............................................................................ 31
4.3.1 Populasi ....................................................................................... 31
4.3.2 Sampel ........................................................................................ 31
4.3.3 Besar Sampel ............................................................................... 31
xiv
4.3.4 Teknik Pengambilan Sampling .................................................... 32
4.3.5 Karakteristik Sampel Penelitian ................................................... 33
4.3.6 Variabel Penelitian ...................................................................... 33
4.3.7 Definisi Operasional .................................................................... 34
4.4. Alat dan Bahan Penelitian .................................................................... 35
4.4.1 Alat Penelitian ............................................................................. 35
4.4.2 Bahan Penelitian .......................................................................... 37
4.5. Prosedur Penelitian ............................................................................... 37
4.5.1 Proses Adaptasi ........................................................................... 37
4.5.2 Pembagian Kelompok Tikus ........................................................ 37
4.5.3 Pemaparan Benzena ..................................................................... 38
4.5.4 Proses Anestesi dan Pengambilan Darah ...................................... 38
4.5.5 Pembuatan Sediaan Hapusan Darah ............................................. 39
4.5.6 Penanganan Hewan Coba Setelah Pengambilan Sampel ............... 39
4.6. Alur Penelitian .................................................................................... 40
4.7. Analisis Data ........................................................................................ 41
4.8 Jadwal Penelitian ................................................................................... 41
BAB V HASIL PENELITIAN DAN ANALISIS DATA ................................... 42
5.1. Hasil Penelitian .................................................................................... 42
5.2. Analisis Data ........................................................................................ 44
5.2.1 Uji One Way ANOVA................................................................... 44
5.2.2 Uji Post Hoc ................................................................................ 46
BAB VI PEMBAHASAN .................................................................................. 48
BAB VII KESIMPULAN DAN SARAN ........................................................... 54
7.1. Kesimpulan .......................................................................................... 54
7.2. Saran .................................................................................................... 54
DAFTAR PUSTAKA ........................................................................................ 55
LAMPIRAN ...................................................................................................... 60
xv
DAFTAR TABEL
Nomor Judul Tabel Halaman
Tabel 2.1 Sifat Fisika dan Kimia Benzena 6
Tabel 2.2 Bentuk Eritrosit Abnormal 16
Tabel 2.3 Klasifikasi Etiologi Anemia Aplastik 22
Tabel 2.4 Keluhan Pasien Anemia Aplastik 24
Tabel 2.5 Klasifikasi Anemia Aplastik 25
Tabel 2.6 Karakteristik Hematologi Tikus dan Manusia 27
Tabel 4.1 Definis Operasional 34
Tabel 4.2 Jadwal Penelitian 41
Tabel 5.1 Hasil Uji Post Hoc Nutrofil Segmen 46
Tabel 5.2 Hasil Uji Post Hoc Limfosit 47
Tabel 5.3 Hasil Uji Post Hoc Monosit 47
xvi
DAFTAR GAMBAR
Nomor Judul Gambar Halaman
Gambar 2.1 Struktur Benzena 5
Gambar 2.2 Metabolisme Benzena 9
Gambar 2.3 Mekanisme Hematotoksisitas Benzena 12
Gambar 2.4 Skema Hematopoiesis di Sumsum Tulang 14
Gambar 2.5 Langkah-Langkah Utama Dalam Produksi Eritrosit 15
Gambar 2.6 Sickled Red Cell, Nucleated red cell (orthochromatic
erythroblast)
17
Gambar 2.7 Sel Target 17
Gambar 2.8 Tear Drop Red Cells, Fragmented Red Cell 17
Gambar 2.9 Nilai Normal Leukosit 20
Gambar 2.10 Platelet Normal 21
Gambar 2.11 Tikus Putih Rattus norvegicus 27
Gambar 4.1 Design Kandang Perlakuan 35
Gambar 5.1 Grafik Rerata differential counting Tiap Kelompok 41
xvii
DAFTAR SINGKATAN
APD : Alat Pelindung Diri
BR-1 : Broiler Starter-1
CYP2E1 : Cytochrome P450 2E1
DNA : Deoxyribonucleic Acid
EDTA : Ethylenediaminetetraacetic Acid
Hb : Hemoglobin
HSC : Hematopoetic Stem Cells
MCV : Mean Corpuscular Volume
NAB : Nilai Ambang Batas
NIOSH : National Institute of Occupational Safety and Health
OSHA : Occupational Safety and Health Administration
PAK : Penyakit Akibat Kerja
Ppm : Part per million
ROS : Reactive Oxygen Species
SPBU : Stasiun Pengisian Bahan Bakar Umum
t,t-MA : t,t muconal acid
xviii
DAFTAR LAMPIRAN
Nomor Judul Lampiran Halaman
Lampiran 1 Uji Normalitas dan Homogenitas 60
Lampiran 2 Uji One Way ANOVA 62
Lampiran 3 Uji Kruskal-Wallis 63
Lampiran 4 Uji Post Hoc Bonferroni 64
Lampiran 5 Uji Post Hoc Mann-Whitney 65
Lampiran 6 Sertifikat Layak Etik 67
Lampiran 7 Surat Ijin Penelitian 68
Lampiran 8 Hasil Plagiasi 69
Lampiran 9 Dokumentasi Kegiatan Penelitian 70
55
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