奥利司他对大鼠非酒精性脂肪肝的保护作用及机制研究

Protective effect and mechanism of orlistat in rats with non-alcoholic fatty liver disease

目的:分析奥利司他对大鼠非酒精性脂肪肝的保护作用及机制。方法:选取30只SD雄性大鼠,随机分为对照组(喂食普通饲料)、模型组(喂食高脂饲料)和奥利司他组(在模型组饲养基础上灌胃60 mg·(kg·d)-1奥利司他),各10只。连续测定各组摄食期间每日摄食量,并在八周后测量增长的体质量、肝脏质量、观察肝脏组织病理变化、并测定甘油三酯(Triglyceride,TG)、谷丙转氨酶(Alanine aminotransferase,ALT)、谷氨酰转移酶(γ-Glutamyltransferase,GGT)、天门冬氨酸氨基转移酶(Aspartate aminotransferase,AST)及空腹血糖(Fiber brag grating,FBG)、空腹胰岛素(Fasting serum lisulin,FINS)、胰岛素敏感指数(ISI)、肝组织磷脂酰肌醇-3激酶(Phosphatidylinositol 3-kinase,PI3K)、蛋白激酶B(Protein kinase B,AKT)蛋白水平。结果:摄食期间三组摄食量、体质量无差异(P>0.05),模型组、奥利司他组肝脏质量高于对照组(P<0.05);奥利司他组肝细胞脂滴较模型组缩小且减少,染色变浅,但仍较对照组深;模型组TG、ALT、GGT、AST高于对照组,奥利司他组TG、ALT、GGT、AST低于模型组(P<0.05);模型组FBG、FINS高于对照组,ISI低于对照组,奥利司他组FBG、FINS低于模型组,ISI高于模型组(P<0.05);模型组肝组织PI3K、AKT蛋白表达水平低于对照组,奥利司他组PI3K、AKT蛋白水平高于模型组(P<0.05)。结论:奥利司他可能通过PI3K/AKT信号通路对NAFLD模型大鼠发挥保护作用,改善其肝脏脂质含量、肝功能酶学指标、血糖水平。

Objective:To analyze the protective effect and mechanism of orlistat in rats with non-alcoholic fatty liver disease.Methods:Thirty SD male rats were selected and randomly divided into control group(feeding with normal diet),model group(feeding with high-fat diet),and orlistat group(feeding with high-fat diet and administrating 60 mg·kg-1·d-1 of orlistat),10 rats in each group.Food intake during feeding were weighed every day,at the end of the 8th week,the increased weight of rat,liver weight,the pathological changes of the liver,triglycerides(TG),alanine aminotransferase(ALT),glutamyl transferase(GGT),aspartate aminotransferase(AST),fasting blood glucose(FBG),fasting insulin(FINS),insulin sensitivity index(ISI)and the protein levels of phosphatidylinositol 3-kinase(PI3K)and protein kinase B(AKT)in liver tissue were determined.Results:Food intake and body weight of the three groups during feeding showed no differences(P>0.05).The liver quality of the model group was higher than that of the control group and that of the orlistat group(P<0.05).Compared with the model group,liver cell lipid droplets shrank and decreased,and the staining becomes lighter in the orlistat group,but it was still darker than that in the control group.TG,ALT,GGT and AST in the orlistat group were lower than those in the model group,and these indicators in the model group were higher than those in the control group(P<0.05).FBG and FINS of the model group were higher than those of the control group,while ISI was lower than that of the control group.FBG and FINS of the orlistat group were lower than those of the model group,and ISI was higher than that of the model group(P<0.05).The protein expression levels of PI3K and AKT in liver tissue of the model group were lower than those in the model group.The protein expression levels of PI3K and AKT in the orlistat group were higher than those in the model group(P<0.05).Conclusion:Orlistat may exert a protective effect on model rats with NAFLD through PI3K/AKT signaling pathway while improving the levels of liver lipids,liver function enzyme parameters,and blood glucose.