阿卡波糖、二甲双胍、吡格列酮对非酒精性脂肪性肝病大鼠肝组织肿瘤坏死因子-α及细胞色素P4502E1的影响  

Influence of Acarbose,Metformin and Pioglitazone on TNF-αand CYP2E1 in Liver Tissue of NAFLD Rat

作　　者：于红艳[1] 张松筠[2] 周晓映[3] 魏红[1] 康亚星[2] 李京芳 魏东敏[1] 刘红[1] 张庆九[2] 

机构地区：[1]河北工程大学附属医院,河北邯郸056006 [2]河北医科大学第二医院,河北石家庄050000 [3]河北省胸科医院,河北石家庄050048 [4]河北省正定县医院,河北石家庄050800

出　　处：《中国药业》2013年第7期11-14,共4页China Pharmaceuticals

基　　金：河北省科技厅计划项目;项目编号:082761010-12

摘　　要：目的观察阿卡波糖、二甲双胍、吡格列酮对非酒精性脂肪性肝病(NAFLD)大鼠肝脏中肿瘤坏死因子-α(TNF-α)、细胞色素P4502E1(CYP2E1)的影响。方法将SD大鼠随机分为正常对照组(普通饲料喂养)、非酒精性脂肪肝组(高脂饮食喂养)、阿卡波糖干预组[高脂饮食喂养加阿卡波糖100 mg/(kg.d)灌胃]、二甲双胍干预组[高脂饮食喂养加二甲双胍500 mg/kg.d)灌胃]、吡格列酮干预组[高脂饮食喂养加吡格列酮15 mg/(kg.d)灌胃]。饲养12周末处死大鼠,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)活性以及总胆固醇(TC)、甘油三酯(TG)、游离脂肪酸(FFA)含量,测量空腹血糖(FBG)及胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR);HE染色观察肝脏病理形态学的变化;Real time PCR和免疫组化法检测肝组织中TNF-α及CYP2E1 mRNA及蛋白表达的变化。结果 3种药物干预组均可降低ALT,AST,ALP活性(P<0.05),减少TC,TG,FFA含量(P<0.05),改善大鼠肝脏病理形态学改变,降低肝脏中TNF-α及CYP2E1 mRNA及蛋白的表达(P<0.01)。二甲双胍、吡格列酮两组间无显著差异(P>0.05),阿卡波糖组的作用明显低于前两者(P<0.01)。结论阿卡波糖、二甲双胍、吡格列酮均可减少TNF-α及CYP2E1的表达,改善非酒精性脂肪肝的病理变化,其中二甲双胍、吡格列酮作用相似,阿卡波糖作用较弱。Objective To observe the influence of acarbose, metformin and pioglitazone on liver tumor necrosis factor- c^（TNF- c^） and cytochrome P4502EI（CYP2E1） in non-alcoholic fatty liver disease（NAFLD） rat. Methods SD rats were randomly divided into five groups： normal control fed with normal diet, non-alcoholic fatty liver group fed with high fat diet, acarbose treatment group fed with high fat diet plus acarbose 100 mg/（kg · d） by lavage, metformin treatment group fed with high fat diet plus metformin 500 mg/（kg · d） by lavage and pioglitazone treatment group fed with high fat diet plus pioglitazone 15 mg/（kg· d） by lavage. The rats were killed at the end of 12 weeks, then the serum contents of alanine transferase （ALT）, aspartate aminotrasferase（AST）, alkaline phosphatase（ALP）, total cholesterol（TC）, total glyceride（TG） and free fatty acid（FFA） were detected; the fasting serum glucose and insulin （FINS） level were measured and the insulin resistance index （HOMA-IR） were calculated; HE staining was carried out to observe the liver patho- logical changes; and the expression level of CYP2EI and TNF- α mRNA and the according protein in liver were measured using real time PCR and immunohistochemistry. Results In all treatment groups, the serum ALT, AST, ALP, TC, TG, FFA, HOMA-IR and the pathological changes of the rat liver were reduced significantly, and the expression of CYP2E1 and TNF- α mRNA and the according protein in the liver reduced. There had no statistical difference between the metformin group and the pioglitazone group, but the effect in the acarbose group was lower than that in the metformin and pioglitazone （P 〈 0.01）. Conclusion For NAFLD rat, acarbose, met- formin and pioglitazone could decrease the expression of CYP2E1 and TNF-α, and alleviate the pathological changes of the rat liver. The effects of metformin and pioglitazone are similar, which of acarbose is weaker.

关 键 词：阿卡波糖 二甲双胍 吡格列酮 非酒精性脂肪性肝病 细胞色素P4502E1 肿瘤坏死因子-Α 

分 类 号：R965.1[医药卫生—药理学] R977.15[医药卫生—药学]