Roux-en-Y胃旁路术对肥胖合并2型糖尿病大鼠肝脂肪代谢的影响和机制探讨  

Effects of Roux-en-Y gastric bypass on hepatic lipid metabolism in obese diabetic rats

作　　者：马南希 马瑞[1] 刘红媛[1] 韩艺 李莹洁 何冰[1] Ma Nanxi;Ma Rui;Liu Hongyuan;Han Yi;Li Yingjie;He Bing(Department of Endocrinology,Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院内分泌科,沈阳110004

出　　处：《中华普通外科杂志》2018年第12期1055-1059,共5页Chinese Journal of General Surgery

基　　金：国家自然基金面上资助项目(81570765);辽宁省科学技术基金资助项目(2015020539).

摘　　要：目的 探讨Roux-en-Y胃旁路手术(Roux-en-Y gastric bypass,RYGB)对肥胖2型糖尿病(type 2 diabetes,T2DM)大鼠肝脏自噬活性的影响和机制.方法 采用高脂饮食联合腹腔注射链脲佐菌素建立肥胖T2DM大鼠模型.将造模成功的T2DM大鼠随机分为糖尿病组、RYGB假手术组和RYGB组,每组8只.采用清醒状态扩展高胰岛素-正血糖钳夹术评估肝脏胰岛素敏感性(insulinsensitivity,IS),酶法检测肝脏组织甘油三酯(triglycerides,TG)含量.Western blot方法检测大鼠肝脏组织中微管相关轻链蛋白(microtubule-associatedprotein 1 light chain 3,LC3)及选择性自噬接头蛋白(sequestosome 1,SQSTM 1/p62)表达.ELISA方法检测血浆中胰高血糖素样肽1(glucagon-like peptide-1,GLP-1)浓度,并与自噬活性进行相关分析.结果 与糖尿病组及RYGB假手术组比较,术后2周RYGB组大鼠肝脏IS上升63%(F=10.87,P<0.01),TG含量下降91% (F=146.3,P<0.01),LC3-Ⅱ/LC3-Ⅰ水平上升(F=17.01,P<0.01),P62蛋白表达下降(F=19.77,P<0.01),血浆中GLP-1浓度提高90% (F=112.8,P<0.01).LC3-Ⅱ/LC3-Ⅰ水平与GLP-1浓度存在显著正相关(r2 =0.66,P=0.0143).结论 RYGB手术上调肝脏自噬活性降低肝脂毒性并改善脂代谢紊乱,术后GLP-1分泌增多可能是激活自噬的机制之一.Objective To explore the effects of Roux-en-Y gastric bypass (RYGB) on hepatic autophagy in obese diabetic rats.Methods Sprague-Dawley diabetes rats were randomly divided into three groups:diabetic group(n =8),diabetic sham RYGB group (n =8) and diabetic RYGB group (n =8).Hyperinsulinemic-euglycemic clamps with tracer infusion were completed to assess insulin sensitivity (IS).Triglyceride (TG) levels in liver tissue were tested.The protein expression levels of P62 (sequestosome 1)and the conversion of LC3 (microtubule-associatedprotein 1 light chain 3) in liver were detected by Western blot.The concentration of glucagon-like peptide-1 (GLP-1) in plasma was detected by ELISA and the correlation between GLP-1 and autophagy was analyzed in 2 weeks after operation.Results In comparison with diabetic and diabetic sham RYGB groups,IS increased by 63% (F =10.87,P < 0.01) and TG content decreased by 91% (F =146.3,P < 0.01) in the liver in RYGB group.In RYGB group,the conversion of LC3-Ⅰ to LC3-Ⅱ raised(F =17.01,P < 0.01),the protein expression of P62 decreased(F =19.77,P <0.01) and the concentration of GLP-1 in plasma increased by 90% (F =112.8,P < 0.01).The marked increase of autophagy in liver after RYGB correlated with the plasma GLP-1 level (r2 =0.66,P =0.014 3)Conclusions RYGB reduces hepatic lipid toxicity and improves lipid metabolism disorder by increasing autophagy,increased GLP-1 secretion after RYGB may be one of the reasons for activating autophagy.

关 键 词：糖尿病 2型 吻合术 ROUX-EN-Y 脂代谢障碍 

分 类 号：R656.6[医药卫生—外科学] R587.1[医药卫生—临床医学]