吡格列酮对非酒精性脂肪性肝病大鼠血小板源生长因子-B和基质金属蛋白酶抑制因子-2表达的影响

目的:观察吡格列酮对非酒精性脂肪性肝病(NAFLD)大鼠肝组织血小板源生长因子B(PDGF-B)和基质金属蛋白酶抑制因子-2(TIMP-2)表达的影响,并研究吡格列酮防治NAFLD发病和进展的疗效及作用机制。方法:选用雄性SD大鼠60只,随机分为正常对照组、模型对照组和吡格列酮组,每组20只。正常对照组大鼠给予普通饲料,其余组均给予高脂饲料;吡格列酮组大鼠在高脂饮食8周后吡格列酮10ml.kg-1.d-1灌胃。于第20周结束时将3组动物处死,取材备检。结果:①肝组织病理变化:模型对照组动物肝细胞均出现中、重度大泡性脂肪变、有明显的炎细胞浸润聚集,吡格列酮组肝细胞也出现较明显的脂肪变和炎症表现,但较模型对照组病变轻。②TIMP-2染色指数3组分别为1.22±0.31,4.52±0.61,1.89±0.45,PDGF-B表达面积3组分别为(0.82±0.13)、(3.79±0.32)、(0.91±0.27)μm2,模型对照组明显高于其他两组(P<0.05),吡格列酮干预后TIMP-2染色指数和PDGF-B表达面积明显降低(P<0.05)。结论:在高脂饮食诱导的NAFLD模型中PDGF-B和TIMP-2表达增强,吡格列酮可以明显改善模型动物肝脏脂肪变性、炎症活动、纤维化变性程度,同时能降低PDGF-B和TIMP-2表达水平,有抗炎、抗纤维化作用。

Effect of Pioglitazone on expression of PDGB-B and TIMP-2 in rats with non-alcoholic fatty liver disease

Objective:To observe the effect of Pioglitazone on the expressions of platelet derived growth factor B(PDGF-B)and tissue inhibitor of metalloproteinase-2(TIMP-2) in the liver of rats with non-alcoholic fatty liver disease(NAFLD),and explore the mechanism of Pioglitazone treating non-alcoholic fatty liver disease.Methods:sixty SD rats were randomly divided into the normal group,the model group and the Pioglitazone group.In normal group rats were fed with Normal diet as controls,NASH model was established by feeding rats with cholesterol-rich diet in model group,and in Pioglitazone group Pioglitazone(10 ml·kg-1·d-1)were given by intragastric administration from the beginning of the eighth week.All the rats were sacrificed at the 20th week.The expression levels of PDGF-B and TIMP-2 were assayed by immunohistological chemistry.Results: ①Hepatic tissue pathological change: there were obvious steatosis in model group and the Pioglitazone group,and steatosis in model group was significantly more serious.Inflammatory reaction was common in the livers of model group,but were seldom seen in normol group.Although some inflammatory cell and cellular necrosis were seen in Pioglitazone group,the severity were more lighter than in model group.②Expression character of TIMP-2 in the normal group,model group and Pioglitazone group,dye index were 1.22±0.31,4.52±0.61,1.89±0.45,the expression of PDGF-B were(0.82±0.13),(3.79±0.32),(0.91±0.27)μm2,there was statistical significance in the normal group and model group(P<0.05).The expression of TIMP-2 and PDGF-B remarkably decreased in Pioglitazone group than those of the model group(P<0.05).Conclusion:PDGF-B and TIMP-2 are increased in steatosis model animals.Pioglitazone not only can decrease levels of serum lipid,but also decrease the expression of liver TIMP-2 and PDGF-B.Pioglitazone not only can improve steatosis,but also delay or/and blocked the development from NASH to liver fibrosis.Perhaps,improved TIMP-2 and PDGF-B level is one of the main mechanism of TZDs protection effect.Pioglitazone can improve NAFLD not only by improve insulin resistance but also anti-inflammatory,antifibrosis.