金芪降糖片调控AMPK/NOX4/IRS1信号通路改善2型糖尿病大鼠肝脏胰岛素抵抗机制研究  

Study on the mechanism of Jinqi Jiangtang Tablet in improving hepatic insulin resistance in type 2 diabetic rat through acting on AMPK/NOX4/IRS1 pathway

作　　者：史丽伟 布天杰 史佩玉 连心逸 张美珍 倪青[1] SHI Liwei;BU Tianjie;SHI Peiyu;LIAN Xinyi;ZHANG Meizhen;NI Qing(Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]中国中医科学院广安门医院内分泌科,北京100053 [2]天津中医药大学第一附属医院内分泌科

出　　处：《环球中医药》2023年第10期1935-1944,共10页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(82174354);北京市自然科学基金(7182143)。

摘　　要：目的金芪降糖片改善2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠肝脏胰岛素抵抗(insulin resistance,IR)作用及作用机制。方法高脂饲料喂养联合链脲佐菌素注射建立T2DM IR模型。T2DM大鼠随机分为模型组、二甲双胍组、金芪降糖片组,干预7周。观察各组大鼠体质量、空腹血糖(fasting blood glucose,FBG)、糖化血红蛋白(hemoglobin a1c,HbA1c)、空腹胰岛素(fasting blood insulin,FINS)、血脂[总胆固醇(total cholesterol,TC)、甘油三酯(triglycerides,TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)]、血清氧化应激指标[超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽(glutathione,GSH)、丙二醛(malonaldehyde,MDA)]、肝功能[谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)]、胰岛素抵抗指数(homeostatic model assessment of insulin resistance,HOMA-IR)变化。用苏木精—伊红染色法(hematoxylin-eosin staining,HE)染色观察胰腺、肝组织形态病理学,肝糖原染色(periodic acid schiff,PAS)观察肝糖原含量。免疫蛋白印迹法检测肝组织腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)、p-AMPK(Thr172)、还原型辅酶Ⅱ氧化酶-4(nicotinamide adenine dinucleotide phosphate oxidase type 4,NOX4)、胰岛素受体底物-1(insulin receptor substrate-1,IRS1)、p-IRS-1(Ser307)蛋白表达情况。结果与空白对照组比较,模型组大鼠体质量明显下降(P<0.05),FBG及HbA1c、FINS、HOMA-IR、TC、TG显著升高(P<0.05);SOD、GSH明显降低而MDA明显升高(P<0.05);ALT、AST无统计学差异(P>0.05);p-AMPK(Thr172)蛋白表达下调而NOX4、p-IRS-1(Ser307)蛋白表达上调(P<0.05)。与对照组比较,模型组大鼠胰岛数目减少,分布稀疏,部分胰岛组织萎缩;肝细胞索排列紊乱,肝细胞多数肿胀,出现中到重度脂肪变性、空泡变性;胞质内糖原颗粒分布明显减少,部分肝Objective To clarify the effects and mechanism of Jinqi Jiangtang Tablet in improving hepatic IR in type 2 diabetic rat.Methods Type 2 diabetes was induced by combined high-fat diet and streptozotocin(STZ)injection in male SD rats.Type 2 diabetic rats were randomly divided into the model group,metformin group and Jinqi Jiangtang Tablet group.The intervention time was seven weeks.The changes of body weight,fasting blood glucose(FBG),hemoglobin a1c(HbA1c),fasting blood insulin(FINS)along with the assessment of HOMA-IR,blood lipid including total cholesterol(TC),triglycerides(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C),serum oxidative stress index including superoxide dismutase(SOD),glutathione(GSH)and malonaldehyde(MDA),and liver function including alanine aminotransferase(ALT),aspartate aminotransferase(AST),were observed in each group.Hematoxylin-ensin(HE)staining was used for pancreas and liver histological analysis.Periodic acid schiff(PAS)staining was used to detect liver glycogen deposits.Western blot was used to detect the relative expression levels of AMP-activated protein kinase(AMPK),p-AMPK(Thr172),nicotinamide adenine dinucleotide phosphate oxidase type 4(NOX4),insulin receptor substrate-1(IRS-1),p-IRS-1(Ser307).Results Compared with the control group,body weight of rats in the model group were decreased significantly(P<0.05).The levels of FBG,HbA1c,FINS,HOMA-IR,TC,TG,and MDA of rats in the model group were significantly increased compared with the control group(P<0.05).The levels of SOD and GSH were significantly decreased while the level of MDA of rats in the model group was significantly increased compared with the control group(P<0.05).There was no significant difference in the levels of ALT and AST between the model group and the control group(P>0.05).Compared with the control group,the expression level of hepatic p-AMPK(Thr172)in the model group was significantly down-regulated,while the expression levels of hepatic NOX4 and p-IRS-1(Ser307)in the mo

关 键 词：金芪降糖片 糖尿病 胰岛素抵抗 肝脏 氧化应激 

分 类 号：R285.5[医药卫生—中药学]