[摘要]目的 观察二甲双胍、吡格列酮及阿卡波糖对糖尿病合并非酒精性脂肪肝病(NAFLD)大鼠肝脏中TNF-α、细胞色素P4502E1(CYP2E1)的影响。方法 高糖高脂饮食8周加腹腔注射小剂量STZ(15 mg/kg)建立T2DM NAFLD模型。造模成功后将大鼠随机分为4组：糖尿病NALFD组(NF，10只，高糖高脂饲料);二甲双胍干预组[DM，10只，高糖高脂饲料加二甲双胍500mg/(kg·d);吡格列酮干预组[DP，10只，高糖高脂饲料加吡格列酮15mg/(kg·d)];阿卡波糖干预组[DA，10只，高糖高脂饲料加阿卡波糖100mg/(kg·d)]。干预4周后应用Real-time PCR和免疫组织化学法检测肝组织中TNF-α、CYP2E1 mRNA及蛋白表达。结果 与NF组比较，DM、DP级DA组的TNF-α及CYP2E1mRNA表达均明显降低(P<0.05)，DM、DP组间差异无统计学意义(P>0.05);DA组降低程度小于DM、DP组(P<0.05)。同时，TNF-α及CYP2E1 蛋白表达呈现相同趋势[(TNF-α：NF(51.86±3.78)%,DM(20.78±2.51)%,DP(19.34±3.17)%,DA(41.37±2.98)%，P<0.05;CYP2E1：NF(33.87±4.15)%，DM(16.78±2.54)%，DP(15.69±1.79)%，DA (22.67±4.02)%，P<0.05)。结论二甲双胍、吡格列酮及阿卡波糖均可减少大鼠肝脏TNF-α、CYP2E1的表达，其中二甲双胍、吡格列酮作用相似，阿卡波糖作用较弱。

　　[关键词]阿卡波糖;二甲双胍;吡格列酮;糖尿病;非酒精性脂肪肝;细胞色素P4502E1;肿瘤坏死因子α

　　[Abstract] Objective To observe the effects of Acarbose, Metformin and Pioglitazone on CYP2E1 and TNF-α in the liver of diabetic rats with non-alcoholic fatty liver disease (NAFLD). Methods Type 2 diabetes NALFD model rats were induced by intraperitoneal injection of Streptozocin (STZ, 15 mg/kg) after high glucose and high fat diet for 8 weeks。After the modeling, rats were randomly divided into 4 groups: Diabetic NAFLD group (DF, n=10, fed with high glucose and high fat diet); Metformin treatment group [DM, n=10, fed with high glucose and high fat diet and 500mg/(kg·d )Metformin]; Pioglitazone treatment group [DP, n=10, fed with high glucose and high fat diet and (15mg/kg·d) Pioglitazone); Acarbose treatment group [DA, n=10, fed with high glucose and high fat diet and 100mg/(kg·d )Acarbose). After treatment for 4 weeks, the expression levels of TNF-α, CYP2E1 mRNA and proteins in liver were measured using Real time PCR and Immunohistochemistry method. Results Compared with group NF，The expression levels of TNF-α and CYP2E1 mRNA in group DM, DP and DA decreased significantly (P<0.05), but there had no significant difference between group DM and DP (P>0.05), and the decreased degree of group DA was much smaller than group DM and DP (P<0.05). Meanwhile，the TNF-α and CYP2E1 protein expression showed the same trend [TNF-α: NF (51.86±3.78)%, DM (20.78±2.51)%, DP(19.34±3.17)%, DA(41.37±2.98)%, P<0.05; CYP2E1: NF(33.87±4.15)%, DM(16.78±2.54)%, DP(15.69±1.79)%, DA(22.67±4.02%), P<0.05. Conclusion Acarbose, Metformin and Pioglitazone could decrease the expression of CYP2E1 and TNF-α in the liver of rats. Metformin and Pioglitazone had similar effects, and are more effective than Acarbose.

　　【Key words】 Metformin; Pioglitazone; Acarbose; Diabetes mellitus; Non-alcoholic fatty liver disease; Cytochrome P4502E1 (CYP2E1); Tumor necrosis factor-α (TNF-α)