二甲双胍对2型糖尿病伴非酒精性脂肪肝大鼠的治疗作用研究  

Effect of metformin on non-alcoholic fatty liver disease in type Ⅱ diabetic rats

作　　者：李忻[1,2] 顾立刚[1] 赵婷婷[2] 张韫[2] 杨鑫[2] 张浩军[2] 严美花[2] 董晞[2] 赵海玲[2] 文玉敏[2] 李平[2] 

机构地区：[1]北京中医药大学抗病毒教育部重点实验室,北京市100029 [2]中日友好医院,北京市100029

出　　处：《广西医学》2015年第3期292-295,共4页Guangxi Medical Journal

基　　金：国家自然科学基金(81173422);国家国际科技合作专项(2011DFA31860)

摘　　要：目的观察二甲双胍对2型糖尿病(T2DM)伴非酒精性脂肪肝(NAFLD)大鼠肝功能及肝组织病理形态学的影响,并探讨其可能的作用机制。方法按随机数字表法将36只Wistar大鼠分成正常组(12只)和造模组(24只),采用小剂量链脲佐菌素腹腔注射加高脂饲料喂养建立T2DM伴NAFLD模型。将造模成功的大鼠随机分为单纯模型组(14只)和二甲双胍组(10只),比较各组大鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、甘油三酯(TG)、总胆固醇(CHO)和低密度脂蛋白胆固醇(LDL-C)水平,肝组织TG、CHO、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、一氧化氮(NO)和一氧化氮合酶(NOS)水平。结果与正常对照组比较,单纯模型组血清ALT、AST、TG、CHO、LDL-C水平均显著升高(P<0.05);肝组织TG、CHO、NO、NOS水平显著升高(P<0.05),SOD及CAT水平降低(P<0.05)。与单纯模型组比较,二甲双胍组血清ALT、AST、TG、CHO、LDL-C水平均显著降低(P<0.05),肝组织TG、CHO、NO、NOS水平显著降低(P<0.05);SOD及CAT水平升高(P<0.05)。结论二甲双胍治疗可显著改善T2DM伴NAFLD大鼠的脂肪肝,其机制可能与二甲双胍改善肝脏组织应激有关。Objective To observe the effects of metfomin on liver function and hepatic pathological morphology in rats with type Ⅱ diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD）, and to explore its possible mechanism. Methods Thirty-six Wistar rats were randomly divided into normal group（n = 12） and model group（ n = 24）. The rat model of T2DM and NAFLD was established by the intraperitoneal injection with a small dose of streptozotocin （STZ） and the fat-rich food feeding. The rats in model group were randomly divided into single model group（ n = 14） and metformin group（ n = 10）. The levels of serum alanine aminotransferase （ALT）, aspartate aminotransferase（AST） ,triglyceride（TG）,cholesterol（CHO）, low density lipoprotein cholesterol（LDL-C） of rats were compared among all groups, as well as the levels of TG, CHO, superoxide dismutase （ SOD）, catalase （ CAT）, nitric oxide （ NO ） and nitric oxide synthase （NOS） in liver tissues. Results Compared with normal group, the levels of serum ALT, AST, TG, CHO and LDL-C increased significantly in the model group （ P 〈 0. 05 ）, as well as the levels of TG, CHO, NO and NOS in liver tissues （ P 〈 0.05 ）, and the levels of SOD and CAT in liver tissues decreased （ P 〈 0.05 ）. The metformin group showed significantly lower levels of serum ALT, AST, TG, CHO and LDL-C compared with single model group （P 〈 0.05）, as well as the levels of TG, CHO, NO and NOS in liver tissues （P 〈 0.05 ）, and the levels of SOD and CAT in liver tissues increased in mefformin group（P 〈0. 05）. Condusion The fatty liver of T2DM rat with NAFLD can be significantly improved by metformin treatment. The mechanism may be related with the improvement of oxidative stress in liver tissues by metformin.

关 键 词：2型糖尿病 非酒精性脂肪肝 二甲双胍 氧化应激 

分 类 号：R965.2[医药卫生—药理学]