| Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease （NAFLD） in rats |
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| 作者姓名： | Xu P Zhang XG Li YM Yu CH Xu L Xu GY |
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| 作者单位： | [1]Department of Gastroenterology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China [2]Department of Pharmacology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China [3]Center of Clinical Laboratory, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China |
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| 摘 要： | Objective： The prevalence of non-alcoholic fatty liver disease （NAFLD） has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone （PGZ） acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding. Methods： The rats were separated randomly into 6 groups： model group Ⅰ were fed high fat diet for 8 weeks, PGZ prevention group were given PGZ 4 mg/（kg.d） simultaneously, while control group Ⅰ were fed normal food for 8 weeks; model group Ⅱ were fed high fat diet for 16 weeks, PGZ treatment group were given PGZ 4 mg/（kg.d） orally simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group Ⅱ were fed normal food for 16 weeks. The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）, tumor necrosis factor alpha （TNF-α）, fasting blood glucose （FBG）, fasting plasma insulin （FINS）, HOMA （homeostasis model assessment） insulin resistance index （HOMA-IR）, and the liver histology of rats of all groups were assayed. Results： After 8 weeks, the liver in model group Ⅰ showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT, AST, ALP, TNF-α were significantly increased （P〈0.05） compared with control group Ⅰ. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased （P〈0.05） compared with model group Ⅰ. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group Ⅱ rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels ofALT, AST, ALP, FINS and HOMA-IR were significantly increased （P〈0.05） in model group Ⅱ compared with control group Ⅱ. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT, ALP, TNF-α and HOMA-IR were significantly decreased compared with model group Ⅱ. Conclusion： Insulin resistance plays a role in the pathogenesis of NAFLD in rats. Pioglitazone can attenuate insulin resistance and biochemical and histological injury in high fat-induced fatty liver in rats.
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| 关 键 词： | 脂肪肝 胰岛素抵抗力 保护效应 NAFLD 大鼠 |
| 收稿时间： | 2006-03-29 |
| 修稿时间： | 2006-06-13 |
Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease (NAFLD) in rats |
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| Xu P,Zhang XG,Li YM,Yu CH,Xu L,Xu GY.Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease (NAFLD) in rats[J].Journal of Zhejiang University Science,2006,7(8):627-633. |
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| Authors: | Ping Xu Xing-guo Zhang You-ming Li Chao-hui Yu Lei Xu Gen-yun Xu |
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| Institution: | (1) Department of Gastroenterology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China;(2) Department of Pharmacology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China;(3) Center of Clinical Laboratory, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China |
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| Abstract: | Objective: The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased. Insulin resistance has been
implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and
NAFLD, and evaluating the role of pioglitazone (PGZ) acting as insulin-sensitizing agents in the prevention and treatment
of rat fatty liver induced by high fat feeding. Methods: The rats were separated randomly into 6 groups: model group I were
fed high fat diet for 8 weeks, PGZ prevention group were given PGZ 4 mg/(kg·d) simultaneously, while control group I were
fed normal food for 8 weeks; model group II were fed high fat diet for 16 weeks, PGZ treatment group were given PGZ 4 mg/(kg·d)
orally simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group II were fed normal food
for 16 weeks. The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities
of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), tumor necrosis factor alpha
(TNF-α), fasting blood glucose (FBG), fasting plasma insulin (FINS), HOMA (homeostasis model assessment) insulin resistance
index (HOMA-IR), and the liver histology of rats of all groups were assayed. Results: After 8 weeks, the liver in model group
I showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum
levels of ALT, AST, ALP, TNF-α were significantly increased (P<0.05) compared with control group I. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver
indexes and serum levels of ALT, ALP were significantly decreased (P<0.05) compared with model group I. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group
II rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels of ALT,
AST, ALP, FINS and HOMA-IR were significantly increased (P<0.05) in model group II compared with control group II. Whereas, in PGZ treatment group, serum levels of AST and FINS showed
decreasing tendency, liver indexes, serum levels of ALT, ALP, TNF-α and HOMA-IR were significantly decreased compared with
model group II. Conclusion: Insulin resistance plays a role in the pathogenesis of NAFLD in rats. Pioglitazone can attenuate
insulin resistance and biochemical and histological injury in high fat-induced fatty liver in rats. |
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| Keywords: | Fatty liver Insulin resistance Pioglitazone |
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