摘要【目的】探讨吡格列酮对SD大鼠非酒精性脂肪肝病（N A FLD ）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。
Abstract：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 giv-en 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 nec-rosis 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 inflam-matory 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 related with the regulation of KCs .
引用本文:
贺丹%李岚%刘慧霞. 吡格列酮对大鼠非酒精性脂肪肝病的治疗作用及其机制[J]. 医学临床研究, 2014, 31(7): 1299-1303.
HE Dan%LI Lan%LIU Huixia. Effect and Mechanism of Pioglitazone for the Treatment of Nonalcoholic Fatty Liver Disease in Rats. 医学临床研究, 2014, 31(7): 1299-1303.
2014, Vol. 31 
