HUBUNGAN ANTARA KADAR HIGH MOLECULAR WEIGHT ADIPONECTIN DENGAN KOMPONEN SINDROM METABOLIK PADA PEREMPUAN MENOPAUSE.
TESIS
PEMBERIAN L-CARNITINE DAPAT
MENGHAMBAT PENINGKATAN JUMLAH
STEATOSIS, KADAR ALT DAN AST TIKUS WISTAR
JANTAN YANG DIBERI MINYAK JELANTAH
SYSKA MARTALA DEWI
PROGRAM PASCASARJANA
UNIVERSITAS UDAYANA
DENPASAR
2016
TESIS
PEMBERIAN L-CARNITINE DAPAT
MENGHAMBAT PENINGKATAN JUMLAH
STEATOSIS, KADAR ALT DAN AST TIKUS WISTAR
JANTAN YANG DIBERI MINYAK JELANTAH
SYSKA MARTALA DEWI
NIM. 1490761013
PROGRAM MAGISTER
PROGRAM STUDI BIOMEDIK-ANTI AGING MEDICINE
UNIVERSITAS UDAYANA
DENPASAR
2016
ii
PEMBERIAN L-CARNITINE DAPAT
MENGHAMBAT PENINGKATAN JUMLAH
STEATOSIS, KADAR ALT DAN AST TIKUS WISTAR
JANTAN YANG DIBERI MINYAK JELANTAH
Tesis untuk Memperoleh Gelar Magister
pada Program Magister, Program Studi Biomedik-Anti Aging Medicine
Program Pascasarjana Universitas Udayana
SYSKA MARTALA DEWI
NIM. 1490761013
PROGRAM MAGISTER
PROGRAM STUDI BIOMEDIK-ANTI AGING MEDICINE
UNIVERSITAS UDAYANA
DENPASAR
2016
iii
Lembar Pengesahan
TESIS INI TELAH DISETUJUI
PADA TANGGAL...................................
Pembimbing I,
Pembimbing II,
Prof. dr. I Gusti Made Aman, Sp. FK
Prof.Dr.dr Wimpie I. Pangkahila, SpAnd, FAACS
NIP. 194606191976021001
NIP. 194612131971071001
Mengetahui
Ketua Program Studi Biomedik-Anti Aging Medicine
Program Pascasarjana
Universitas Udayana
Dr. dr. Gde. Ngurah Indraguna Pinatih, M.Sc, Sp. GK
NIP. 195805211985031002
DAFTAR ISI
Halaman
SAMPUL DALAM ................................................................................ .....
ii
LEMBAR PENGESAHAN ................................................................... .....
iv
PENETAPAN PENGUJI .............................................................................
v
SURAT PERNYATAAN BEBAS PLAGIAT ....................................... .....
vi
UCAPAN TERIMA KASIH .......................................................................
vii
ABSTRAK .............................................................................................. .....
x
ABSTRACT ................................................................................................
xi
DAFTAR ISI ...............................................................................................
xii
DAFTAR TABEL .......................................................................................
xv
DAFTAR GAMBAR ...................................................................................
xvi
DAFTAR SINGKATAN .............................................................................
xvii
BAB I
BAB II
PENDAHULUAN .......................................................................
1
1.1 Latar Belakang ....................................................................
1
1.2 Rumusan Masalah ...............................................................
8
1.3 Tujuan Penelitian ................................................................
9
1.4 Manfaat penelitian...............................................................
9
KAJIAN PUSTAKA ...................................................................
11
2.1 Penuaan ...............................................................................
11
2.2 Minyak Jelantah .................................................................
15
2.2.1 Definisi minyak jelantah ...........................................
15
2.2.2 Dampak minyak jelantah terhadap kesehatan ...........
19
2.3 Hati .....................................................................................
22
2.3.1 Fisiologi hati .............................................................
22
2.3.2 Anatomi dan histologi hati........................................
24
2.3.3 Patologi hati ..............................................................
27
2.3.4 Parameter klinis kerusakan hati ................................
29
2.4 Non-alcoholic Fatty Liver Diseases (NAFLD) ..................
30
2.5 L-Carnitine .........................................................................
36
2.5.1 Peranan L-Carnitine dalam metabolisme lemak.......
37
2.5.2 L-Carnitine sebagai antioksidan ...............................
42
2.6 Hewan Coba .......................................................................
42
BAB III KERANGKA BERPIKIR, KONSEP DAN HIPOTESIS ...........
44
3.1 Kerangka Berpikir ...............................................................
44
3.2 Konsep Penelitian ...............................................................
46
3.3 Hipotesis Penelitian.............................................................
47
BAB IV METODE PENELITIAN ............................................................
48
4.1 Rancangan Penelitian ..........................................................
48
4.2 Tempat dan Waktu Penelitian .............................................
49
4.3 Populasi dan Sampel ...........................................................
49
4.3.1 Populasi.....................................................................
49
4.3.2 Kriteria sampel ..........................................................
49
4.3.3 Penentuan Besaran sampel .......................................
50
4.4 Variabel ...............................................................................
50
4.5 Definisi operasional variabel ..............................................
51
4.6 Alat dan Bahan ....................................................................
52
4.7 Prosedur Penelitian .............................................................
53
4.7.1. Penentuan dosis minyak jelantah....... .......................
53
4.7.2. Persiapan penelitian....... ...........................................
54
4.7.3 Pelaksanaan penelitian ..... ........................................
54
4.8 Alur Penelitian...... ...............................................................
56
ii
4.9 Analisis Data...... .................................................................
57
HASIL PENELITIAN .................................................................
58
5.1 Analisis Deskriptif ..............................................................
58
5.2 Uji Normalitas Data ............................................................
61
5.3 Uji Homogenitas Data .........................................................
62
5.4 Uji Komparabilitas ..............................................................
62
5.4.1 Uji Komparabilitas Jumlah Steatosis ........................
62
4.3.2 Uji Komparabilitas Kadar ALT ................................
64
4.3.3 Uji Komparabilitas Kadar AST ................................
65
BAB VI PEMBAHASAN .........................................................................
68
6.1 Subyek Penelitian ................................................................
68
6.2 Distribusi dan Homogenitas Data Hasil Penelitian .............
68
6.3 Pengaruh Pemberian L-Carnitine terhadap Jumlah
Steatosis, Kadar ALT dan AST...........................................
69
BAB VII SIMPULAN DAN SARAN ........................................................
75
7.1 Simpulan .............................................................................
75
7.2 Saran....................................................................................
75
DAFTAR PUSTAKA ..................................................................................
76
LAMPIRAN
87
BAB V
...........................................................................................
DAFTAR TABEL
iii
Tabel
Halaman
5.1 Hasil Analisis Deskriptif Data Jumlah Steatosis……..………….……
60
5.2
Hasil Analisis Deskriptif Data Kadar ALT dan AST .........................
60
5.3
Hasil Uji Normalitas Data Antar Kelompok ......................................
61
5.4
Hasil Uji Homogenitas Data Antar Kelompok ...................................
62
5.5 Komparasi Rerata Jumlah Steatosis antar Kelompok..………….……
63
5.6
Komparasi Rerata Kadar ALT antar Kelompok .................................
64
5.7
Komparasi Rerata Kadar AST antar Kelompok .................................
66
iv
DAFTAR GAMBAR
Gambar
Halaman
2.1 Fungsi Utama Hati dalam Tubuh …………………..………….……
24
2.2
Anatomi Hati Tikus ...........................................................................
25
2.3
Histologi hati Tikus ..........................................................................
27
2.4
Diagram Hipotesis “two-hit theory” Patogeneis NAFLD ..................
32
2.5
Gambaran Histopatologi Hati yang mengalami Steatosis .. ...............
35
2.6
Struktur Kimia Molekul L-Carnitine ……… .....................................
36
2.7
Peran L-Carnitine dalam Metabolisme Lipid ………….. ..................
38
3.1
Konsep Penelitian ...............................................................................
46
4.1
Rancangan Penelitian .........................................................................
48
4.2
Alur Penelitian ....................................................................................
56
5.1
Histopatologi Jaringan Hati Kelompok Kontrol (P0) .........................
59
5.2
Histopatologi Jaringan Hati Kelompok Perlakuan (P1) .....................
59
5.3
Grafik Perbandingan Rerata Jumlah Steatosis....................................
63
5.4
Grafik Perbandingan Rerata Kadar ALT ............................................
65
5.5
Grafik Perbandingan Rerata Kadar AST ............................................
67
v
DAFTAR SINGKATAN
A4M
: American Academy of Anti-Aging Medicine
AAM
: Anti Aging Medicine
ALT
: Alanin aminotransaminase
AST
: Aspartat Transaminase
FLD
: Fatty Liver Disease
FSH
: Follicle Stimulating Hormone
GH
: Growth Hormone
HDL
: High Density Lipoproteins
IGF-1
: Insulin Growth Factor-1
LDL
: Low Density Lipoproteins
LH
: Luteinizing Hormone
MDA
: Malondialdehid
NAFLD
: Nonalcoholic Fatty Liver Disease
NASH
: Nonalcoholic Steatohepatitis
SOD
: Superoxide Dismutase
vi
PEMBERIAN L-CARNITINE DAPAT
MENGHAMBAT PENINGKATAN JUMLAH
STEATOSIS, KADAR ALT DAN AST TIKUS WISTAR
JANTAN YANG DIBERI MINYAK JELANTAH
SYSKA MARTALA DEWI
PROGRAM PASCASARJANA
UNIVERSITAS UDAYANA
DENPASAR
2016
TESIS
PEMBERIAN L-CARNITINE DAPAT
MENGHAMBAT PENINGKATAN JUMLAH
STEATOSIS, KADAR ALT DAN AST TIKUS WISTAR
JANTAN YANG DIBERI MINYAK JELANTAH
SYSKA MARTALA DEWI
NIM. 1490761013
PROGRAM MAGISTER
PROGRAM STUDI BIOMEDIK-ANTI AGING MEDICINE
UNIVERSITAS UDAYANA
DENPASAR
2016
ii
PEMBERIAN L-CARNITINE DAPAT
MENGHAMBAT PENINGKATAN JUMLAH
STEATOSIS, KADAR ALT DAN AST TIKUS WISTAR
JANTAN YANG DIBERI MINYAK JELANTAH
Tesis untuk Memperoleh Gelar Magister
pada Program Magister, Program Studi Biomedik-Anti Aging Medicine
Program Pascasarjana Universitas Udayana
SYSKA MARTALA DEWI
NIM. 1490761013
PROGRAM MAGISTER
PROGRAM STUDI BIOMEDIK-ANTI AGING MEDICINE
UNIVERSITAS UDAYANA
DENPASAR
2016
iii
Lembar Pengesahan
TESIS INI TELAH DISETUJUI
PADA TANGGAL...................................
Pembimbing I,
Pembimbing II,
Prof. dr. I Gusti Made Aman, Sp. FK
Prof.Dr.dr Wimpie I. Pangkahila, SpAnd, FAACS
NIP. 194606191976021001
NIP. 194612131971071001
Mengetahui
Ketua Program Studi Biomedik-Anti Aging Medicine
Program Pascasarjana
Universitas Udayana
Dr. dr. Gde. Ngurah Indraguna Pinatih, M.Sc, Sp. GK
NIP. 195805211985031002
DAFTAR ISI
Halaman
SAMPUL DALAM ................................................................................ .....
ii
LEMBAR PENGESAHAN ................................................................... .....
iv
PENETAPAN PENGUJI .............................................................................
v
SURAT PERNYATAAN BEBAS PLAGIAT ....................................... .....
vi
UCAPAN TERIMA KASIH .......................................................................
vii
ABSTRAK .............................................................................................. .....
x
ABSTRACT ................................................................................................
xi
DAFTAR ISI ...............................................................................................
xii
DAFTAR TABEL .......................................................................................
xv
DAFTAR GAMBAR ...................................................................................
xvi
DAFTAR SINGKATAN .............................................................................
xvii
BAB I
BAB II
PENDAHULUAN .......................................................................
1
1.1 Latar Belakang ....................................................................
1
1.2 Rumusan Masalah ...............................................................
8
1.3 Tujuan Penelitian ................................................................
9
1.4 Manfaat penelitian...............................................................
9
KAJIAN PUSTAKA ...................................................................
11
2.1 Penuaan ...............................................................................
11
2.2 Minyak Jelantah .................................................................
15
2.2.1 Definisi minyak jelantah ...........................................
15
2.2.2 Dampak minyak jelantah terhadap kesehatan ...........
19
2.3 Hati .....................................................................................
22
2.3.1 Fisiologi hati .............................................................
22
2.3.2 Anatomi dan histologi hati........................................
24
2.3.3 Patologi hati ..............................................................
27
2.3.4 Parameter klinis kerusakan hati ................................
29
2.4 Non-alcoholic Fatty Liver Diseases (NAFLD) ..................
30
2.5 L-Carnitine .........................................................................
36
2.5.1 Peranan L-Carnitine dalam metabolisme lemak.......
37
2.5.2 L-Carnitine sebagai antioksidan ...............................
42
2.6 Hewan Coba .......................................................................
42
BAB III KERANGKA BERPIKIR, KONSEP DAN HIPOTESIS ...........
44
3.1 Kerangka Berpikir ...............................................................
44
3.2 Konsep Penelitian ...............................................................
46
3.3 Hipotesis Penelitian.............................................................
47
BAB IV METODE PENELITIAN ............................................................
48
4.1 Rancangan Penelitian ..........................................................
48
4.2 Tempat dan Waktu Penelitian .............................................
49
4.3 Populasi dan Sampel ...........................................................
49
4.3.1 Populasi.....................................................................
49
4.3.2 Kriteria sampel ..........................................................
49
4.3.3 Penentuan Besaran sampel .......................................
50
4.4 Variabel ...............................................................................
50
4.5 Definisi operasional variabel ..............................................
51
4.6 Alat dan Bahan ....................................................................
52
4.7 Prosedur Penelitian .............................................................
53
4.7.1. Penentuan dosis minyak jelantah....... .......................
53
4.7.2. Persiapan penelitian....... ...........................................
54
4.7.3 Pelaksanaan penelitian ..... ........................................
54
4.8 Alur Penelitian...... ...............................................................
56
ii
4.9 Analisis Data...... .................................................................
57
HASIL PENELITIAN .................................................................
58
5.1 Analisis Deskriptif ..............................................................
58
5.2 Uji Normalitas Data ............................................................
61
5.3 Uji Homogenitas Data .........................................................
62
5.4 Uji Komparabilitas ..............................................................
62
5.4.1 Uji Komparabilitas Jumlah Steatosis ........................
62
4.3.2 Uji Komparabilitas Kadar ALT ................................
64
4.3.3 Uji Komparabilitas Kadar AST ................................
65
BAB VI PEMBAHASAN .........................................................................
68
6.1 Subyek Penelitian ................................................................
68
6.2 Distribusi dan Homogenitas Data Hasil Penelitian .............
68
6.3 Pengaruh Pemberian L-Carnitine terhadap Jumlah
Steatosis, Kadar ALT dan AST...........................................
69
BAB VII SIMPULAN DAN SARAN ........................................................
75
7.1 Simpulan .............................................................................
75
7.2 Saran....................................................................................
75
DAFTAR PUSTAKA ..................................................................................
76
LAMPIRAN
87
BAB V
...........................................................................................
DAFTAR TABEL
iii
Tabel
Halaman
5.1 Hasil Analisis Deskriptif Data Jumlah Steatosis……..………….……
60
5.2
Hasil Analisis Deskriptif Data Kadar ALT dan AST .........................
60
5.3
Hasil Uji Normalitas Data Antar Kelompok ......................................
61
5.4
Hasil Uji Homogenitas Data Antar Kelompok ...................................
62
5.5 Komparasi Rerata Jumlah Steatosis antar Kelompok..………….……
63
5.6
Komparasi Rerata Kadar ALT antar Kelompok .................................
64
5.7
Komparasi Rerata Kadar AST antar Kelompok .................................
66
iv
DAFTAR GAMBAR
Gambar
Halaman
2.1 Fungsi Utama Hati dalam Tubuh …………………..………….……
24
2.2
Anatomi Hati Tikus ...........................................................................
25
2.3
Histologi hati Tikus ..........................................................................
27
2.4
Diagram Hipotesis “two-hit theory” Patogeneis NAFLD ..................
32
2.5
Gambaran Histopatologi Hati yang mengalami Steatosis .. ...............
35
2.6
Struktur Kimia Molekul L-Carnitine ……… .....................................
36
2.7
Peran L-Carnitine dalam Metabolisme Lipid ………….. ..................
38
3.1
Konsep Penelitian ...............................................................................
46
4.1
Rancangan Penelitian .........................................................................
48
4.2
Alur Penelitian ....................................................................................
56
5.1
Histopatologi Jaringan Hati Kelompok Kontrol (P0) .........................
59
5.2
Histopatologi Jaringan Hati Kelompok Perlakuan (P1) .....................
59
5.3
Grafik Perbandingan Rerata Jumlah Steatosis....................................
63
5.4
Grafik Perbandingan Rerata Kadar ALT ............................................
65
5.5
Grafik Perbandingan Rerata Kadar AST ............................................
67
v
DAFTAR SINGKATAN
A4M
: American Academy of Anti-Aging Medicine
AAM
: Anti Aging Medicine
ALT
: Alanin aminotransaminase
AST
: Aspartat Transaminase
FLD
: Fatty Liver Disease
FSH
: Follicle Stimulating Hormone
GH
: Growth Hormone
HDL
: High Density Lipoproteins
IGF-1
: Insulin Growth Factor-1
LDL
: Low Density Lipoproteins
LH
: Luteinizing Hormone
MDA
: Malondialdehid
NAFLD
: Nonalcoholic Fatty Liver Disease
NASH
: Nonalcoholic Steatohepatitis
SOD
: Superoxide Dismutase
vi