二甲双胍对糖尿病大鼠心肌病变抗氧化保护作用.docVIP

二甲双胍对糖尿病大鼠心肌病变抗氧化保护作用 　【摘要】 目的 探讨二甲双胍(MT)对2型糖尿病大鼠心肌病变的抗氧化保护作用。方法 雄性SD大鼠45只，高脂高糖喂养6周后，予以链脲佐菌素(STZ)35mg/kg腹腔注射制备2型糖尿病动物模型，随机分为对照组(CG)、单纯糖尿病组(DG)、小剂量MT干预组(SM，100mg/kg·d灌胃)及大剂量MT干预组(LM，300mg/kg.d灌胃)，灌胃12周后，血清检测胰岛素(INS)、甘油三酯(TG)、总胆固醇(T-CH)及游离脂肪酸(FFA)，心肌匀浆检测超氧化物歧化酶(SOD)及丙二醛(MDA)水平，应用免疫组织化学方法测定核因子(NF-κB p65)及环氧化酶-2(COX-2)在心肌中的表达，并观察各组心肌细胞超微结构变化。结果 1)与对照组比较，DG组体重明显减轻，血糖、心脏质量指数、INS、TG、T-CH及FFA明显升高(P＜0.01)；应用MT治疗后体重无明显增加，INS有所下降，心脏质量指数、血糖、TG及FFA明显降低(P＜0.01)；DG组心肌组织MDA明显升高，SOD明显降低(P＜0.01)，MT治疗后上述指标明显改善；2)超微结构观察单纯糖尿病组肌丝结构明显紊乱，典型肌小节结构消失，线粒体肿胀、间质纤维增生，微血管内皮细胞肿胀等表现，而SM及LM组可见组织结构有所改善；3)对照组心肌NF-κB p65及COX-2只有少量表达，单纯糖尿病组表达量明显增多(P＜0.01)，MT治疗后表达量明显减少(P＜0.01)。结论 MT对糖尿病心肌病变具有保护作用，可能与其减弱脂质的过氧化反应，减少NF-κB及COX-2的表达有关。 【关键词】 二甲双胍；糖尿病大鼠；心肌；抗氧化 　　Obstract： Objective To explore the protective effect and investigate anti-oxidative stress mechanism of metformin on diabetic myocardial damage in rats. Methods The model of diabetes in 45 male SD rats was establised through intraperitoneal injection streptozotoch(STZ) 35mg/kg after six weeks by feeding high fat and high glucose food. 45 rats were randomly divided into control group group(CG)、Diabetic group(DG)、small dose metformin group(SM,intragastric administration with metformin 100mg/kg·d）and large dose metformin group(LM, intragastric administration with metformin 300mg/kg.d ).All groups was taken blood sample to detecte insulin 、blood fat and free fatty acids and prepared myocardium homogenate to detecte activity of superoxide dismutate (SOD) and malondialdehyde(MDA) and analyze the express of NF-κB p65 and COX-2 in myocardium by immunohistochemical analysis,observe myocardial ultrastructure at the end of 12 weeks. Results 1)compared with the control group,body weight decreased significantly and blood glucose 、heart index 、insulin、cholesterol、triglyeride and free fatty acids in DG group increased significantly（P＜0.01）. Compared with DG group, the level of insulin , heart index 、blood glucose、triglyeride and free fatty acids were cut down signifi