PENGARUH KADAR KOLESTEROL TOTAL DAN GULA

DARAH PUASA TERHADAP PENURUNAN REFERENCE

MEMORY PADA TIKUS WISTAR JANTAN DAN BETINA

YANG DIINDUKSI DIET TINGGI LEMAK

SKRIPSI

ATTAUFIQ IRAWAN

1510211022

UNIVERSITAS PEMBANGUNAN NASIONAL “VETERAN” JAKARTA

FAKULTAS KEDOKTERAN

PROGRAM STUDI SARJANA KEDOKTERAN

2019

i

PENGARUH KADAR KOLESTEROL TOTAL DAN GULA

DARAH PUASA TERHADAP PENURUNAN REFERENCE

MEMORY PADA TIKUS WISTAR JANTAN DAN BETINA

YANG DIINDUKSI DIET TINGGI LEMAK

SKRIPSI

Diajukan Sebagai Salah Satu Syarat Untuk Memperoleh

Gelar Sarjana Kedokteran

ATTAUFIQ IRAWAN

1510211022

UNIVERSITAS PEMBANGUNAN NASIONAL “VETERAN” JAKARTA

FAKULTAS KEDOKTERAN

PROGRAM STUDI SARJANA KEDOKTERAN

2019

v

PENGARUH KADAR KOLESTEROL TOTAL DAN GULA

DARAH PUASA TERHADAP PENURUNAN REFERENCE

MEMORY PADA TIKUS WISTAR JANTAN DAN BETINA

YANG DIINDUKSI DIET TINGGI LEMAK

Attaufiq Irawan

Abstrak

Obesitas telah menjadi pandemi yang ditandai dengan berbagai komplikasi

kesehatan dan penyakit komorbid. Salah satu penyebab pandemi ini adalah

meningkatnya pola diet yang tidak sehat seperti diet tinggi lemak. Berbagai studi

menunjukan bahwa konsumsi diet tinggi lemak, menyebabkan gangguan kognitif.

Peningkatan kadar kolesterol dan insensitivitas reseptor insulin diduga dapat

menyebabkan gangguan konsolidasi memori. Studi yang membahas pengaruh

peningkatan kadar kolesterol dan disregulasi glukosa terhadap gangguan memori

masih terbilang jarang. Tujuan penelitian ini mengetahui pengaruh perubahan

kadar glukosa darah puasa dan kolesterol total terhadap penurunan reference

memory pada tikus Wistar jantan dan betina yang diinduksi diet tinggi lemak.

Kadar kolesterol total dan gula darah puasa diukur menggunakan spektrometer

dan error reference memory diukur menggunakan labirin delapan lengan. Desain

penelitian ini adalah eksperimen dengan jumlah sampel sebesar 24 tikus Wistar.

Hasil menunjukkan terdapat hubungan antara peningkatan kolesterol total

(p=0,000) dan gula darah puasa (p=0,005) dengan peningkatan error reference

memory, serta tidak terdapat hubungan antara jenis kelamin (p=0,385) dan berat

badan dengan peningkatan error reference memory (p=0,099). Peningkatan

kolesterol total merupakan faktor yang paling berpengaruh (59,7 kali) dalam

meningkatkan error reference memory.

Kata Kunci : Kolesterol, gula darah, diet tinggi lemak, reference memory.

vi

THE EFFECT OF TOTAL CHOLESTEROL AND FASTING

BLOOD GLUCOSE LEVEL ON DECREASING OF

REFERENCE MEMORY ON MALE AND FEMALE WISTAR

RATS INDUCED BY HIGH FAT DIET

Attaufiq Irawan

Abstract

Obesity has become a pandemic characterized by various health complications

and comorbid diseases. One of the causes of this pandemic is increasingly

unhealthy diet patterns such as high-fat diets. Various studies show that the

consumption of a high-fat diet causes cognitive impairment. Increased cholesterol

levels and insensitivity of insulin receptors are thought to cause impaired memory

consolidation. Studies that discuss the effect of increasing cholesterol levels and

glucose dysregulation on memory disorders are still fairly rare. The purpose of

this study was to determine the effect of changes in fasting blood glucose levels

and total cholesterol on decreasing reference memory in male and female Wistar

rats induced by a high-fat diet. Total cholesterol and fasting blood glucose levels

were measured using a spectrometer and a reference memory error was measured

using an eight-arm maze. The design of this study was an experiment with a

sample size of 24 Wistar rats. The results showed that there was a correlation

between the increase in total cholesterol (p = 0,000) and fasting blood glucose (p

= 0,005) with an increase in reference memory error, and there was no

relationship between sex (p = 0,385) and body weight with an increase in

reference memory error (p = 0.099). Increasing total cholesterol is the most

influential factor (59,7 times) in increasing the reference memory error.

Keywords: Cholesterol, blood glucose, high fat diet, reference memory.

vii

KATA PENGANTAR

Puji syukur penulis panjatkan ke hadirat Allah SWT, karena berkat rahmat

Nya-lah penulis dapat menyelesaikan skripsi dengan judul “Pengaruh kadar

kolesterol total dan gula darah puasa terhadap penurunan reference memori pada

tikus wistar jantan dan betina yang diinduksi diet tinggi lemak”. Penulis

menyadari bahwa banyak pihak terkait yang telah memberikan bantuan sejak

dimulainya masa perkuliahan hingga saat ini. Oleh karena itu penulis ingin

menyampaikan rasa hormat dan terima kasih yang sebesar-besarnya kepada Dr.

dr. Prio Sidipratomo, Sp. Rad, selaku Dekan Fakultas Kedokteran UPNVJ, dr.

Niniek Hardini, Sp. PA, selaku ketua Program Studi Sarjana Kedokteran, dr. Tuty

Rizkianti, Sp. PD, selaku dosen pembimbing utama, Ibu Meiskha Bahar, S.Si,

selaku dosen pembimbing kedua yang telah bersedia meluangkan waktu, tenaga,

dan pikiran untuk mengarahkan serta memberi dukungan dan perhatian yang

sangat besar pada peneliti selama proses penyusunan skripsi ini, dan dr. Muttia

Amalia, M. Biomed, selaku penguji utama yang telah memberikan masukan,

saran, dan motivasi yang sangat bermanfaat dalam penyusunan skripsi ini, juga

kepada orang tua peneliti, Letkol CHB Bambang Irawan dan Krismiyati, kak Asri

dan Astri yang selalu memberikan dukungan di setiap langkah yang saya ambil.

Tidak lupa sahabat terbaik peneliti: Amed, Aldi, Maul, Daniel, Faiz, Izzy,

Shabrina, Toga. Terimakasih atas hiburan, dukungan, perhatian, dan

pengertiannya. Serta pihak-pihak lain yang tidak dapat peneliti sebutkan satu

persatu, untuk bantuan dan kontribusi yang diberikan kepada peneliti demi

kelancaran penulisan skripsi serta kehidupan perkuliahan yang peneliti lalui di FK

UPNVJ. Peneliti berharap semoga Allah SWT berkenan membalas segala

kebaikan semua pihak yang telah membantu. Semoga penelitian ini dapat

bermanfaat.

viii

DAFTAR ISI

HALAMAN JUDUL ................................................................................................ i

PERNYATAAN ORISINALITAS ......................................................................... ii

PERNYATAAN PERSETUJUAN PUBLIKASI .................................................. iii

PENGESAHAN ..................................................................................................... iv

ABSTRAK .............................................................................................................. v

ABSTRACT ........................................................................................................... vi

KATA PENGANTAR .......................................................................................... vii

DAFTAR ISI ........................................................................................................ viii

DAFTAR TABEL .................................................................................................. xi

DAFTAR BAGAN ............................................................................................... xii

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

DAFTAR LAMPIRAN ........................................................................................ xiii

BAB I PENDAHULUAN ....................................................................................... 1

I.1 Latar Belakang ................................................................................................... 1

I.2 Rumusan Masalah .............................................................................................. 3

I.3 Tujuan Penelitian ............................................................................................... 3

I.3.2 Tujuan Khusus ................................................................................................ 3

I.4 Manfaat Penelitian ............................................................................................. 4

I.4.1 Manfaat Teoritis .............................................................................................. 4

I.4.2 Manfaat Praktis ............................................................................................... 4

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

II.1 Landasan Teori ................................................................................................. 5

II.1.1 Kolesterol ...................................................................................................... 5

II.1.2 Glukosa Darah ............................................................................................. 13

II.1.3 Insulin .......................................................................................................... 16

II.1.4 Memori ........................................................................................................ 17

II.1.5 Pengaruh diet tinggi lemak terhadap memori .............................................. 25

II.2 Kerangka Teori ............................................................................................... 29

II.3 Kerangka Konsep ........................................................................................... 30

ix

II.4 Hipotesis Penelitian ........................................................................................ 30

II.5 Penelitian Terkait............................................................................................ 31

BAB III METODOLOGI PENELITIAN.............................................................. 33

III.1 Jenis Penelitian .............................................................................................. 34

III.2 Lokasi dan Waktu Penelitian ........................................................................ 34

III.3 Subjek Penelitian ........................................................................................... 34

III.4 Kriteria Penelitian ......................................................................................... 34

III.4.1 Kriteria Inklusi ........................................................................................... 34

III.4.1 Kriteria Eksklusi......................................................................................... 34

III.5 Besar Sampel ................................................................................................. 35

III.6 Variabel Penelitian ........................................................................................ 35

III.6.1 Variabel Bebas ........................................................................................... 35

III.6.2 Variabel Terikat ......................................................................................... 35

III.7 Definisi Operasional ..................................................................................... 36

III.8 Instrumen Penelitian...................................................................................... 37

III.8.1 Alat ............................................................................................................. 37

III.8.2 Bahan.......................................................................................................... 37

III.9 Alur Penelitian .............................................................................................. 38

III.10 Persiapan dan Perlakuan Pengujian ............................................................ 39

III.10.1 Sebelum Perlakuan ................................................................................... 39

III.10.2 Perlakuan pada Hewan Uji ....................................................................... 40

III.10.3 Setelah Perlakuan ..................................................................................... 40

III.11 Teknik Analisa Data .................................................................................... 41

III.11.1 Analisis Univariat..................................................................................... 41

III.11.2 Analisis Bivariat ....................................................................................... 41

III.11.3 Analisis Multivariat .................................................................................. 41

III.12 Etika Penelitian ........................................................................................... 41

BAB IV HASIL DAN PEMBAHASAN .............................................................. 44

IV.1 Hasil Penelitian ............................................................................................. 44

IV.2 Hasil Analisis Univariat ................................................................................ 44

IV.2.1 Sebaran Data Numerik Variabel Bebas ..................................................... 44

IV.2.3 Hasil berat badan........................................................................................ 44

IV.2.4 Hasil Glukosa Darah .................................................................................. 45

x

IV.2.5 Hasil Kolesterol ......................................................................................... 46

IV.2.6 Hasil Error Reference Memory .................................................................. 47

IV.3 Hasil Analisis Bivariat .................................................................................. 48

IV.3.1 Hasil Uji Normalitas .................................................................................. 49

IV.3.2 Hasil Uji Korelasi Pearson ......................................................................... 49

IV.3.3 Hasil Uji T Independen .............................................................................. 50

IV.4 Hasil Analisis Multivariat ............................................................................. 51

IV.5 Pembahasan................................................................................................... 53

IV.5.1 Pembahasan Hasil Analisis Univariat ........................................................ 53

IV.5.2 Pembahasan Hasil Analisis Bivariat .......................................................... 55

IV.5.3 Pembahasan Hasil Analisis Multivariat ..................................................... 57

IV.6 Keterbatasan Penelitian ................................................................................. 58

BAB V PENUTUP ................................................................................................ 59

V.1 Kesimpulan .................................................................................................... 59

V.2 Saran ............................................................................................................... 59

RIWAYAT HIDUP ............................................................................................... 69

Lampiran ............................................................................................................... 71

xi

DAFTAR TABEL

Tabel 1 Kadar Glukosa Darah Puasa ........................................................................ 16

Tabel 2 Penelitian Terkait .............................................................................. 30

Tabel 3 Definisi Operasional .......................................................................... 35

Tabel 4 Gambaran Sebaran Data Numerik Variabel Bebas ............................ 43

Tabel 5 Hasil Berat Badan Sebelum dan Setelah Pemberian Diet Tinggi

Lemak ....................................................................................... ……. 43

Tabel 6 Hasil Glukosa Darah Puasa Sebelum dan Setelah Pemberian Diet

Tinggi Lemak ............................................................................ ……. 44

Tabel 7 Hasil Kolesterol Total Sebelum dan Setelah Pemberian Diet

Tinggi Lemak ............................................................................ ……. 45

Tabel 8 Hasil Berat Badan Sebelum dan Setelah Pemberian Diet Tinggi

Lemak ....................................................................................... ……. 46

Tabel 9 Rerata Error Referece Memory Sebelum dan Setelah Pemberian Diet

Tinggi Lemak ............................................................................ ……. 47

Tabel 10 Uji Normalitas ................................................................................... 48

Tabel 11 Uji Korelasi Pearson ......................................................................... 49

Tabel 12 Uji T Independen Perbedaan Error Reference Memory antara Tikus

Jantan dan Betina ............................................................................... 50

Tabel 13 Ringkasan Hasil Uji Regresi Linier .................................................. 50

xii

DAFTAR BAGAN

Bagan 1 Ringkasan pembentukan kolesterol .................................................. 5

Bagan 2 Model Klasifikasi Memori Menurut Squire ...................................... 18

Bagan 3 Kerangka Teori ................................................................................. 29

Bagan 4 Kerangka Konsep .............................................................................. 30

Bagan 5 Alur Penelitian .................................................................................. 37

xiii

DAFTAR GAMBAR

Gambar 1 Nasib kilomikron remnan ............................................................... 9

Gambar 2 Nasib VLDL ................................................................................... 9

Gambar 3 Fungsi dan nasib HDL.................................................................... 10

Gambar 4 Pembentukan memory trace ........................................................... 21

Gambar 5 Pembentukan plak aterosklerosis ................................................... 26

Gambar 6 Efek influks 27-hydroxycholesterol ke dalam otak ........................ 27

Gambar 7 Insulin-like Growth Factors di otak dan implikasi klinisnya ......... 28

xiv

DAFTAR LAMPIRAN

Lampiran 1 Surat Persetujuan Proposal Penelitian

Lampiran 2 Surat Persetujuan Etik

Lampiran 3 Gambar-gambar Penelitian

Lampiran 4 Hasil Data Penelitian

Lampiran 5 Hasil Analisis Data