胃转流术对非肥胖型2型糖尿病大鼠骨骼肌组织中MG53蛋白表达的影响  

Influence on expression of MG53 protein in skeletal muscle tissue of non-obese type 2 diabetic mellitus rats after gastric bypass operation

作　　者：龚帅 张蓬波 张冲 吴耐 张易 张秀忠 孟凡超 祁彦韦 任泽强 GONG Shuai;ZHANG Pengbo;ZHANG Chong;WU Nai;ZHANG Yi;ZHANG Xiuzhong;MENG Fanchao;QI Yanwei;REN Zeqiang(Department of General Surgery,Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu 221000,P.R.China;Graduate School of Xuzhou Medical University,Xuzhou,Jiangsu 221002,P.R.China)

机构地区：[1]徐州医科大学附属医院普外科,江苏徐州221000 [2]徐州医科大学研究生学院,江苏徐州221002

出　　处：《中国普外基础与临床杂志》2020年第4期448-453,共6页Chinese Journal of Bases and Clinics In General Surgery

基　　金：徐州市科技计划项目(项目编号:KC16SL113)。

摘　　要：目的研究胃转流术对非肥胖型2型糖尿病(T2DM)大鼠骨骼肌组织中E3泛素连接酶—mitsugumin53(MG53)蛋白及其mRNA,以及胰岛素受体底物1(IRS-1)mRNA表达的影响,探讨胃转流术改善骨骼肌胰岛素抵抗的可能机制。方法将24只雄性GK大鼠随机分为糖尿病手术组、糖尿病假手术组及糖尿病对照组,每组8只,若大鼠死亡,则重新制备模型补充;另外以8只Wistar大鼠作为正常对照组。应用Westem blot技术检测4组大鼠术后第8周时骨骼肌组织中MG53蛋白的表达水平,应用RT-PCR技术检测4组大鼠术后第8周时骨骼肌组织中IRS-1 mRNA和MG53 mRNA的表达水平。结果①糖尿病假手术组及糖尿病对照组大鼠的MG53 mRNA及其蛋白的表达水平均高于正常对照组和糖尿病手术组(P<0.05),但糖尿病手术组和正常对照组间比较、糖尿病假手术组和糖尿病对照组间比较差异均无统计学意义(P>0.05)。②与正常对照组比较,糖尿病手术组、糖尿病假手术组及糖尿病对照组大鼠的IRS-1 mRNA的表达水平均较低(P<0.05),但糖尿病手术组、糖尿病假手术组及糖尿病对照组大鼠的IRS-1 mRNA的表达水平比较差异无统计学意义(P>0.05)。结论胃转流术降低了非肥胖型T2DM大鼠骨骼肌组织中IRS-1蛋白的E3泛素连接酶—MG53蛋白的表达水平,减少了IRS-1蛋白的泛素化降解,这可能是骨骼肌胰岛素信号通路中IRS-1蛋白表达上调的主要机制之一,从而改善了骨骼肌的胰岛素抵抗,降低了血糖。Objective To observe expressions of E3 ubiquitin ligase—mitsugmin53(MG53)protein,MG53 mRNA,and insulin receptor substrate 1(IRS-1)mRNA in skeletal muscle of non-obese type 2 diabetic mellitus(T2DM)rats after gastric bypass operation(GBP),and to investigate possible mechanism of GBP in improving insulin resistance.Methods Twenty-four healthy male GK rats were randomly divided into diabetic operation group,diabetic sham operation group,and diabetic control group,8 rats in each group;besides,8 male Wistar rats were served as normal control group.The expressions of MG53 protein in skeletal muscle tissue were detected by using Western blot method on week 8 after operation.The mRNA levels of IRS-1 and MG53 in skeletal muscles tissue were measured by RT-PCR methods on week 8 after operation.Results①The expressions of MG53 protein and MG53 mRNA in the diabetic sham operation group and diabetic control group were significantly higher than those in the diabetic operation group and the normal control group on week 8 after operation(P<0.05),respectively,which had no significant differences between the diabetic operation group and the normal control group(P>0.05),and between the diabetic sham operation group and the diabetic control group(P>0.05)on week 8 after surgery.②Compared with the normal control group,the expression of IRS-1 mRNA was significantly decreased in the diabetic operation group,the diabetic sham operation group,and the diabetic control group(P<0.05),while there were no significant differences between the diabetic operation group,diabetic sham operation group,and the diabetic control group on week 8 after operation(P>0.05).Conclusion Expression of E3 ubiquitin ligase—MG53 protein in skeletal muscle tissue in T2DM rats following GBP is decreased,thus reduces the IRS-1 ubiquitin-degradation,increase the expression of IRS-1 protein in insulin signaling pathway of skeletal muscle tissue,and improve insulin resistance of skeletal muscle.

关 键 词：2型糖尿病 胃转流术 MG53 胰岛素受体底物-1 E3泛素连接酶 胰岛素抵抗 

分 类 号：R587.1[医药卫生—内分泌]