艾塞那肽治疗肥胖症的机制研究  

Study of mechanism of exenatide in the treatment of obesity

作　　者：叶志伟[1,2] 冼颖欣 陈宗兰 林倍思[1] 徐芬[1] 姚斌[1] Ye Zhiwei;Xian Yingxin;Chen Zonglan;Lin Beisi;Xu Fen;Yao Bin(Department of Endocrinology and Metabolism,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院内分泌与代谢病学科,广州510630 [2]中山大学附属第三医院急诊医学科,广州510630 [3]济宁医学院附属医院内分泌科,济宁272000

出　　处：《新医学》2020年第10期780-785,共6页Journal of New Medicine

摘　　要：目的探讨艾塞那肽治疗肥胖症的机制及其相互关系。方法选择15只雄性C57BL/6小鼠随机分为对照组、高脂饮食肥胖模型组(模型组)和高脂饮食肥胖模型艾塞那肽治疗组(治疗组)。在实验第16周记录各组小鼠摄食量、体质量、体脂量,测量空腹血糖,进行腹腔内葡萄糖耐量试验(GTT)和胰岛素耐量试验(ITT)。测量后处死小鼠,收集小鼠血清、脂肪组织检测胰岛素信号通路分子、炎症和氧化应激指标。结果肥胖指标方面,模型组小鼠的进食量、体脂量、体脂百分比均高于对照组(P均<0.017),治疗组进食量少于模型组(P<0.017)。糖代谢方面,模型组小鼠的空腹血糖、GTT及ITT血糖曲线下面积均高于对照组(P<0.017),治疗组小鼠的空腹血糖、GTT及ITT血糖曲线下面积均较模型组有所下降但与模型组比较差异无统计学意义(P均>0.017)。胰岛素信号通路分子检测中,模型组IRS1磷酸化比例(p-IRS1/IRS1)低于对照组(P<0.017),治疗组p-IRS1/IRS1较模型组回升(P<0.017)。在炎症和氧化应激指标方面,模型组的血清IL-6水平高于对照组(P<0.017),治疗组的HIF-1αmRNA相对表达量较模型组下降(P<0.017)。3组动物模型合并计算,血清IL-6水平(r=0.702,P=0.011)和脂肪组织IL-6 mRNA相对表达量(r=0.590,P=0.043)均与体脂百分比呈正相关。血清IL-6水平还与进食量(r=0.670,P=0.017)、脂肪量(r=0.680,P=0.015)和空腹血糖(r=0.780,P=0.003)呈正相关。脂肪组织IL-6与eNOS mRNA相对表达量呈正相关(r=0.627,P=0.029)。脂肪组织的HIF-1α相对表达量与ITT血糖曲线下面积(r=0.643,P=0.024)呈正相关,与p-IRS1(r=-0.820,P=0.046)和p-IRS1/IRS1(r=-0.846,P=0.034)呈负相关。结论艾塞那肽可改善肥胖小鼠模型的肥胖指标和相关的糖代谢异常,这种疗效可能是通过抗炎和抗氧化应激实现的。Objective To explore the specific mechanism of exenatide in treating obesity and investigate its relationship.Methods Fifteen male C57BL/6 mice were randomly divided into the normal control group,obesity model group(induced by high-fat diet)and exenatide treatment group(treated by exenatide after high-fat diet).At the 16th week of the experiment,the food intake,body weight,weight of body fat,and fasting blood glucose of the mice in each group were recorded,and intraperitoneal glucose tolerance test(GTT)and insulin tolerance test(ITT)were performed.Subsequently,the mice were sacrificed,and the adipose tissue and serum of the mice were collected to detect the insulin signaling pahway molecules and measure the indexes of inflammation and oxidative stress.Results In terms of the obsesity indexes,the food intake,weight and percentage of body fat in the obesity model group were significantly higher compared with those in the control group(all P<0.017),and the food intake in the treatment group was considerably less than that in the model group(P<0.017).In the model group,the area under the ROC curve of fasting blood glucose,GTT and ITT was remarkably larger than that in the control group(all P<0.017).Regarding the glucose metabolism,the area under the ROC curve of fasting blood glucose,GTT and ITT in the treatment group was slightly smaller than that in the model group with no statistical significance(all P>0.017).In the model group,the percentage of IRS1 phosphorylation was significantly lower than that in the control group(P<0.017).In the treatment group,the percentage of IRS1 phosphorylation was significantly higher than that in the model group(P<0.017).The IL-6 level in the model group was significantly higher than that in the control group(P<0.017).In the treatment group,the relative expression level of HIF-1αmRNA was significantly down-regulated compared with that in the model group(P<0.017).For all the animals in three groups,the serum IL-6 levels(r=0.702,P=0.011)and the relative expression levels of IL-6 mRNA

关 键 词：艾塞那肽 肥胖 炎症 氧化应激 

分 类 号：R589.2[医药卫生—内分泌]