吡格列酮对大鼠非酒精性脂肪肝病的治疗作用及其机制

【目的】探讨吡格列酮对SD大鼠非酒精性脂肪肝病（NAFLD ）的治疗作用及其机制。【方法】36只雄性SD大鼠随机分为正常对照组（NG组）、吡格列酮治疗组（PIOG组）及高脂饮食组（FG组），均饲养12周；NG组喂饲普通饲料，剩余两组喂饲高脂饲料；PIOG组于实验第8～12周予吡格列酮灌胃，其余两组同期予蒸馏水灌胃；比较三组空腹血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、三酰甘油（TG）、总胆固醇（TC）、空腹血糖（FPG）、空腹胰岛素（FINS）、空腹胰岛素抵抗指数（FIRI）、肿瘤坏死因子-α（TNF-α）及一氧化氮（NO）的水平；HE染色分析肝组织切片病理学改变；观察Kupffer细胞（KCs）形态变化。【结果】FG组大鼠FIRI、TG、TC均高于NG组，其差异均有统计学意义（ P ＜0．05），肝组织呈大泡性脂肪变性并出现炎症细胞浸润及点状坏死，肝脏KCs发生形态改变，其产生的TNF、NO水平与肝组织病理学改变呈正相关（ P ＜0．05）；PIOG组大鼠 FIRI、TG、TC均低于FG组，其差异均有统计学意义（ P ＜0．05），肝组织脂肪变性程度减轻，仍可见炎症细胞浸润和肝细胞气球样变性，肝脏KCs形态及功能仍存在异常。【结论】吡格列酮可部分延缓高脂饮食诱导的NAFLD的进展；其机制可能与改善胰岛素抵抗、降低血脂有关，与调节KCs功能无关。

Effect and Mechanism of Pioglitazone for the Treatment of Nonalcoholic Fatty Liver Disease in Rats

Objective To explore the effect and mechanism of pioglitazone for the treatment of nonalcoholic fatty liver disease（NAFLD） in rats .Methods] Thirty six male SD rats were randomly divided into normal control group （group NG） ,pioglitazone treatment group（group PIOG） and high-fat diet group（group FG） .All rats were fed for 12 weeks .Group NG was fed with standard diet ,and the rest two groups were fed with high-fat diet .Group PIOG was given pioglitazone by lavage at 8～12 weeks ,while other 2 groups were given distilled water by lavage in the same period . The levels of fasting serum alanine aminotransferase（ALT） ,aspartate aminotransferase（AST） ,triglycerides（TG） ,total cholesterol（TC） ,fasting glucose（FPG） ,fasting blood insulin（FINS） ,fasting insulin resistance index （FIRI） ,tumor necrosis factor-α（TNF-α） and nitric oxide（NO） were compared among 3 groups .HE staining method was used to analyze the pathologic change of hepatic tissue section .The morphological change of Kupffer cells （KCs） was observed .Results]The levels of FIRI ,TG and TC in group FG were higher than those in group NG ,and there was significant difference （ P〈0 .05） .Hepatic tissues showed big bubble fatty degeneration ,inflammatory cell infiltration and dot-like necrosis .KCs in liver tissue had morphological change .The levels of TNF and NO produced by KCs were positively correlated with pathological changes of liver tissue（ P〈0 .05） .The levels of FIRI ,TG and TC in group PIOG were lower than those in group FG ,and there was significant difference （ P〈0 .05） .The degree of liver steatosis was improved ,but the inflammatory cell infiltration and hepatocyte ballooning degeneration were still visible .The shape and function of liver KCs were still abnormal .Conclusion]Pioglitazone can partly delay the development of NAFLD induced by high-fat diet .The mech-anism may be associated with the improvement of insulin resistance and the decreasing of blood lipids ,but not