TUGAS AKHIR PENELITIAN

PENGARUH INDUKSI ALUMUNIUM KLORIDA (AlCl3) TERHADAP

FUNGSI MEMORI PADA TIKUS PUTIH (rattus norvegicus strain wistar)

MODEL HIPOESTEROGEN

Oleh:

Irma Aulia

201610330311072

FAKULTAS KEDOKTERAN

UNIVERSITAS MUHAMMADIYAH MALANG

2019

ii

HASIL PENELITIAN

PENGARUH INDUKSI ALUMUNIUM KLORIDA (AlCl3) TERHADAP

FUNGSI MEMORI PADA TIKUS PUTIH (rattus norvegicus strain wistar)

MODEL HIPOESTEROGEN

KARYA TULIS AKHIR

Diajukan kepada

Universitas Muhammadiyah Malang

untuk Memenuhi Salah Satu Persyaratan

dalam Menyelesaikan Program Sarjana

Fakultas Kedokteran

Oleh:

Irma Aulia

NIM. 201610330311072

FAKULTAS KEDOKTERAN

UNIVERSITAS MUHAMADIYAH MALANG

2019

iii

LEMBAR PENGESAHAN

LAPORAN HASIL PENELITIAN

Telah Disetujui Sebagai Hasil Penelitian Untuk Memenuhi Persyaratan

Pendidikan Sarjana Fakultas Kedokteran

Universitas Muhammadiyah Malang

Tanggal : 26 Desember 2019

Pembimbing I

dr. Kusuma Andriana, Sp.OG

NIP 0725096801

Pembimbing II

dr. Rahayu, Sp.S

NIP. 11307040456

Mengetahui,

Fakultas Kedokteran Universitas Muhammdiyah Malang

Dekan,

Dr. dr. Meddy Setiawan, Sp.PD.FINASIM

NIP : 19680521 200501 100

iv

PERNYATAAN ORISINALITAS

Karya tulis akhir ini adalah karya saya sendiri, dan semua sumber baik yang

dikutip maupun dirujuk telah saya nyatakan dengan benar.

Nama : Irma Aulia

NIM : 201610330311072

v

LEMBAR PENGUJIAN

Karya Tulis Akhir oleh Irma Aulia ini

telah diuji dan dipertahankan didepan Tim Penguji

pada tanggal : 26 Desember 2019

Tim Penguji

dr. Kusuma Andriana, Sp.OG , Ketua

dr. Rahayu, Sp.S , Anggota

dr. Hanna Cakrawati, M.Biomed , Anggota

vi

KATA PENGANTAR

Bismillahirohmanirrohim,

Alhamdulillah, Puji syukur saya ucapkan kepada Allah SWT karena atas

karunia dan nikmat-Nya penulis dapat menyelesaikan karya tulis akhir ini yang

berjudul “Pengaruh Induksi Alumunium Klorida (AlCl3) Terhadap Fungsi

Memori (rattus novergicus strain wistar) Model Hipoesterogen”.

Penyusunan karya tulis akhir ini dimaksudkan untuk memenuhi salah satu

syarat mendapatkan gelar Sarjana Kedokteran Jurusan Pendidikan Dokter di

Fakultas Kedokteran Universitas Muhammadiyah Malang. Penyusunan karya tulis

ini telah banyak mendapat bantuan serta bimbingan. Oleh sebab itu, penulis

mengucapkan rasa terimakasih kepada :

1. Dr. dr. Meddy Setiawan, Sp.PD, FINASIM selaku Dekan Fakultas

Kedokteran Universitas Muhammadiyah Malang.

2. dr. Moch. Maroef, Sp.OG selaku Wakil Dekan I Fakultas Kedokteran

Universitas Muhammadiyah Malang.

3. dr. Sri Adila Nurainiwati, Sp.KK selaku Wakil Dekan II Fakultas

Kedokteran Universitas Muhammadiyah Malang.

4. dr. Indra Setiawan, SP.THT selaku Wakil Dekan III Fakultas Kedokteran

Universitas Muhammadiyah Malang.

5. Dr. Kusuma Andriana, Sp.OG selaku pembimbing 1 yang telah

meluangkan waktu untuk membimbing, memberi dukungan, pencerahan,

memberi saran, dan kesabaran yang telah diberikan.

vii

6. dr. Rahayu Gunardjo, Sp.S selaku pembimbing 2 yang penuh kesabaran

membimbing, memberi saran, terimakasih atas ketelitiannya dalam

penulisan saya.

7. dr. Hanna Cakrawati, M.Biomed sebagai penguji

8. Orang tua, terima kasih banyak ayah yang selalu siap menjadi pendengar

selama perkuliaahan dan siap menjadi tempat berkeluh kesah setiap saat.

Terima kasih kepada ummi yang doanya selalu menyertai dalam

pelaksanaan perkuliaahan terutama saat menjalankan skripsi.

9. Sahabat dan teman-teman yang selalu bersedia menerima keluh kesah saya

tentang skripsi Arum, Erca, Savira Sal, Savira nov, dian, dede, ririn.

10. Teman-teman kelompok skripsi yang bersedia menjadi teman diskusi :

Aga, Laras..

11. Pulmo yang telah mendukung, memberi bunga, dan kado.

Saya mengharapkan semoga karya tulis akhir ini dapat bermanfaat bagi

masyarakat dan pihak terkait. Saya menyadari bahwa penulisan karya tulis akhir

ini masih jauh dari kata sempurna. Oleh sebab itu, saya mengharapkan kritik serta

saran yang membangun guna kesempurnaan karya tulis akhir ini.

Malang, 19 Desember 2019

Penulis

viii

ABSTRAK

Aulia, Irma. 2019. Pengaruh Induksi Alumunium Klorida (AlCl3) Terhadap

Fungsi Memori Tikus Putih rattus novergicus strain wistar Model

Hipoesterogen, Karya Tulis Akhir.Fakultas Kedokteran, Universitas

Muhammadiyah Malang. Pembimbing : (1) (Kusuma Andriana) *(2)

(Rahayu)**

Latar belakang : Kemajuan teknologi dalam bidang kedokteran memberikan

dampak angka harapan hidup meningkat. Hal ini meningkatkan kejadian penyakit

neurodegeneratif, contohnya Alzheimer’s Disease (AD) . Perempuan memiliki

angka harapan hidup lebih tinggi dibanding laki-laki, menyebabkan usia

perempuan lebih panjang hal ini menyebabkan masa menopausenya lebih

panjang. AD adalah penyakit degeneratif yang menyebabkan penurunan fungsi

memori. Sampai saat ini etiologinya masih belum ditemukan, tetapi salah satu

studi menyebutkan bahwa alumunium adalah faktor risiko AD.

Tujuan : Untuk mengetahui pengaruh induksi AlCl3 terhadap fungsi memori

pada rattus novergicus model hipoesterogen.

Metode : : Dilakukan ovariektomi pada 4 kelompok tikus setalah 4 minggu, lalu

diinduksi AlCl3. Untuk mengetahui pengaruh AlCl3, perbedaan dosis (50,100,dan

200 mg/Kg per oral selama 42 hari) digunakan. Performa dari tikus diperiksa

dengan melakukan pemeriksaan morris water maze pada ke 38-42. Setelah

dilakukan pemeriksaan morris water maze, waktu yang diperlukan untuk

mencapai hidden platform selanjutnya dihitung.

Hasil penelitian dan diskusi : Hasil menunjukkan bahwa pemberian dosis AlCl3

100mg/KgBB mengalami penurunan yang signifikan dibandingkan dengan

pemberian dosis (50,100,200mg/KgBB) + ovariektomi. Hal ini mungkin karena

berbagai faktor, seperti cahaya, luas maze dan bisa saja terjadi atypical

alzheimer,s disease dimana otak sudah mengalami atrofi tetapi tidak menunjukkan

gejala.

Kesimpulan : Pada penelitian ini didapatkan bahwa pemberian AlCl3

100mg/KgBB selama 6 minggu menunjukkan penurunan fungsi memori yang

signifikan.

Kata Kunci : AlCl3, Alzheimer, Ovariektomi

(*) : Staff Pengajar Fakultas Kedokteran UMM

(**) : Staff Pengajar Fakultas Kedokteran UMM

ix

ABSTRACT

Aulia, Irma. 2019. The effect of Alumunium Chloride ( AlCl3) On Memory

Function of White Rat rattus novergicus strain wistar Hipoesterogen

Model, Thesis, Medical Faculty, University Of Muhammadiyah Malang.

Advisor (1) (Kusuma Andriana)*(2) ( Rahayu)

Background : A better technology especially in medical sector make life

expectancy increased. It makes neurodegenerative issue increase, for exmpale

alzheimer’s disease (AD). Woman have a longer life expectency compare to man,

cause woman have a longer life, thus make menapuasal period longer. AD is a

degenerative disease that cause decrease in memory function. Until now the

etiology is still unclear, but one of studies said that alumunium is a risk factor for

AD.

Aim: To know the influence of AlCl3 induction towards memory function in rattus

novergicus hypoestrogen model

Method: Do ovariectomy in rat, then after 4 weeks induce AlCl3To know the

influence of AlCl3, the dosage difference (50,100 and 200 mg/Kg orally for 42

days) is used. The perform of rat is checked using morris water maze examination

in the day 38-42 of experiment. After the morris water maze examination,

calculated the time to reach the hidden platform

Result: Result shows that dosage 100mg/Kg of AlCl3 sustain a significant

decrease in memory function compare to dosage (50,100,200 mg/Kg) +

ovariectomy. This matter probably causes by many factors such as light, the size

of maze and atypical alzheimers disease that could happen when the brain is

already atrophy but show no symptoms.

Conclusions: In this experiment shows that induction of AlCl3100mg/Kg for 6

weeks sustain a significant decrease in memory function

Key Word : AlCl3, Alzheimer, Ovariectomy

(*) : Lecturer in Medical Faculty, UMM

(**) : Lecturer in Medical Faculty, UMM

x

DAFTAR ISI

JUDUL DALAM…………………………………………………………………..i

HALAMAN PRASYARAT GELAR……………………………………………..ii

LEMBAR PENGESAHAN ………………………………..………………….....iii

HALAMAN PERNYATAAN ORIGINALITAS……………………….……......iv

LEMBAR PENGUJI….………………………………………………………......v

KATA PENGANTAR…………………………………………………………....vi

ABSTRAK……………………………………………………………………....viii

ABSTRACT……………………………………………………………………...ix

DAFTAR ISI……………………………………………..……………………….x

DAFTAR TABEL……………………………………….……………………....xii

DAFTAR GAMBAR ........................................................................................... xiii

DAFTAR SINGKATAN ..................................................................................... xiv

DAFTAR LAMPIRAN…………………..………………………………………xv

BAB I PENDAHULUAN ....................................................................................... 2

1.1. Latar Belakang ......................................................................................... 2

1.2. Rumusan Masalah .................................................................................... 4

1.3. Tujuan Penelitian ...................................................................................... 5

1.3.1. Tujuan umum .................................................................................... 5

1.3.2. Tujuan Khusus .................................................................................. 5

1.4. Manfaat Penelitian .................................................................................... 5

1.4.1. Bagi Akademis .................................................................................. 5

1.4.2. Bagi Klinis ........................................................................................ 5

BAB II TINJAUAN PUSTAKA ............................................................................. 5

2.1. Hipoesterogen ........................................................................................... 5

2.1.1. Definisi dan etiologi .......................................................................... 5

2.1.2. Fungsi Esterogen ............................................................................... 6

2.2. Fungsi Memori ......................................................................................... 8

2.2.1. Definisi .............................................................................................. 8

2.2.2. Fisiologi dan Proses Memori ............................................................ 9

2.2.3. Pusat Memori .................................................................................. 14

2.2.4. Cara pemeriksaan ............................................................................ 18

2.3. Alzheimer…………………………………………………………………..20

2.3.1. Definisi ............................................................................................ 20

2.3.2. Epidemiologi ................................................................................... 20

2.3.3. Neuropathologi ................................................................................ 22

2.3.4. Manifestasi Klinis ........................................................................... 25

2.3.5. Diagnosis…………………………………………………………..28

2.3.6. Faktor Risiko ................................................................................... 29

BAB III KERANGKA KONSEP DAN HIPOTESIS PENELITIAN .................. 35

3.1. Kerangka Konsep ................................................................................... 35

3.2. Hipotesis ................................................................................................. 37

BAB IV Metode Penelitian ................................................................................... 38

4.1. Jenis Penelitian ........................................................................................... 38

4.2. Lokasi dan waktu Penelitian………………………………………………38

4.3. Populasi dan Sampel………………………………………………………38

4.3.1. Populasi ........................................................................................... 38

4.3.2. Sampel ............................................................................................. 38

4.3.3. Besar Sampel ................................................................................... 38

4.3.4. Teknik Pengambiln Sampel………………………………………..40

xi

4.3.5. karakteristik sampel penelitian ........................................................ 40

4.3.6. Variabel Penelitian……………………………………………………41

4.3.7. Definisi oprasional .......................................................................... 41

4.4. Alat dan Bahan ....................................................................................... 42

4.4.1. Alat .................................................................................................. 42

4.4.2. Bahan............................................................................................... 43

4.5. Prosedur penelitian ................................................................................. 44

4.5.1. Aklimatisasi .................................................................................... 44

4.5.2. Ovariektomi..................................................................................... 44

4.5.3. Pap Smear……………………………………………………………..45

4.5.4. Induksi……………………………………………………………..46

4.5.5. Tes memori...................................................................................... 46

4.6. Pengolahan dan analisis data .................................................................. 47

4.7. Alur penelitian ........................................................................................ 48

BAB V HASIL PENELITIAN DAN ANLISA DATA……………….….……..49

5.1. Hasil Penelitian………………………………………………………...49

5.2. Analisa Penelitian……………………………………………………...52

BAB VI PEMBAHASAN……………………………………………………....55

BAB VII KESIMPULAN DAN SARAN…………………………………..…...63

7.1. Kesimpulan…………………………………………………………….63

7.1. Saran………….……………………………………………………….63

DAFTAR PUSTAKA…………………………………………………………...65

LAMPIRAN…………………………………………………………………….72

xii

DAFTAR TABEL

Nomor Judul Tabel Halaman

Tabel 2.1. Jumlah Penderia Dementia di Negara Miskin, Negara

Berkembang dan Negara Maju……………………………….21

Tabel 4.1. Definisi Oprasional……………………………………………42

Tabel 5.1. Pengaruh pemberian AlCl3 terhadap rerata waktu yang

diperlukan untuk menemukan hidden platfor (detik)…….…..50

xiii

DAFTAR GAMBAR

Nomor Judul Gambar Halaman

Gambar 2.1. Struktur Memori…………………………………….………….10

Gambar2.2. Mekanisme Sensitisasi dan Habituasi …...……………………..12

Gambar2.3. Formatio Hipokampus .…………………………………………16

Gambar 2.4. Serebelum………………..……………………………………..17

Gambar 2.5. Morris Water Maze…………………………………………………..19

Gambar 5.1.Rerata Waktu Yang Diperlukan Untuk Menemukan Hidden

Platform (detik)………………………………………………….51

xiv

DAFTAR SINGKATAN

AD : Alzheimer’s Disease

STM : Sort Term Memory

LTM : Long Term Memory

ER : Esterogen Reseptor

APP : Amyloid Protein Precursor

ChAt : Choline Acetyltransferase

LNT : The Linear Non-Threshold

IR : Ion Radiation

PS : Preselin

APOE : Apolipoproten E

MRI : Magnetic Imaging Responding

NMDA : N-Metil-D-asparat

SSP : Sistem Saraf Pusat

PSEN : Presenelin

CREB : cAMP Responsive Element Binding Protein

OVX : Ovariektomi

xv

DAFTAR LAMPIRAN

Nomor Lampiran Halaman

Lampiran 1 Hasil Uji Statistik SPSS………………………………………….72

Lampiran 2 Dokumentasi Penelitian………………………………………...78

Lampiran 3 Hasil Sitologi Vagina…………………………………………….81

Lampiran 4 Keterangan Layak Etik…………………………………………..83

Lampiran 5 Berkas Ijin Penelitian…………………………………………….84

Lampiran 6 Surat Keterangan Bimbingan Metpen…………………………...85

Lampiran 7 Lembar Konsultasi………………………………………………86

Lampiran 8 Surat Pernyataan………………………………………………...87

Lampiran 9 Hasil Plagiasi……………………………………………………88

65

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