Roux-en-Y胃旁路术对2型糖尿病大鼠肾脏早期损害的保护作用  

Protective Effect of Roux-en-Y Gastric Bypass Surgery on Early Damage of Renal Tissue in Type 2 Diabetes Mellitus Rats

作　　者：文艺[1] 祁巧 刘丹青[1] 黄尚清 林宁[1] 石力[1] 陈涛[1] 汤礼军[1] 

机构地区：[1]成都军区总医院全军普外中心 [2]95879部队门诊部

出　　处：《中国普外基础与临床杂志》2015年第4期404-411,共8页Chinese Journal of Bases and Clinics In General Surgery

基　　金：全军临床高新技术重大项目(项目编号:2010gxjs040)~~

摘　　要：目的探讨胃转流术对2型糖尿病大鼠肾脏早期损害的保护作用及其可能的作用机理。方法采用高脂饮食加腹腔注射小剂量(35 mg/kg)链脲佐菌素(streptozocin,STZ)方法建立2型糖尿病大鼠模型。将造模成功的糖尿病大鼠按数字表法随机分为3组:糖尿病对照组(n=8)、假手术组(n=8)和Roux-en-Y胃旁路手术组(n=14);另取正常SD大鼠作为正常对照组(n=8)。分别于术前和术后8周检测各组大鼠的空腹血糖、血清总胆固醇(TC)、甘油三酯(TG)和游离脂肪酸(FFA)水平;于术前和术后4及8周测定各组大鼠血清尿素氮(BUN)和肌酐(Cr);于术前和术后8周测定各组大鼠24 h尿微量白蛋白和尿8-羟基脱氧鸟酐;于术后8周取肾组织进行病理组织学观察,计算肾重指数、肾小球平均截面积(MGA)及肾小球平均体积(MGV),并采用免疫组化方法检测肾组织纤连蛋白(FN)、Ⅳ型胶原(CoⅣ)、转化生长因子-β1(TGF-β1)、细胞间黏附分子-1(ICAM-1)、还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(NOX4)和Bcl-2蛋白的表达。结果 Roux-en-Y胃旁路术能显著降低糖尿病大鼠血糖、血脂、肾重指数、MGA和MGV(P<0.05),改善肾脏病理形态和肾脏功能(P<0.05),减少FN及CoⅣ蛋白的表达,降低TGF-β1、NOX4和ICAM-1在肾脏皮质的表达,同时增加Bcl-2蛋白的表达(P<0.05)。结论胃旁路术可改善糖尿病大鼠的肾脏功能,改善其病理损害,其机理可能与抑制TGF-β1、NOX4和ICAM-1蛋白的表达和上调Bcl-2蛋白的水平有关。Objective To investigate the protective effect of Roux-en-Y gastric bypass surgery on early damage of renal tissue in type 2 diabetes mellitus rats, and explore the mechanism of the protective effects. Methods Diabetes mellitus animal models were induced by intraperitoneal injection of streptozotocin（STZ, 35 mg /kg） and a high-fat diet. Diabetic rats were divided into three groups randomly（digital table method）： diabetes control group（n=8）, sham operation group（n=8）, and Roux-en-Y gastric bypass group（n=14）. Another 8 normal SD rats as the normal control group. The fasting blood glucose, serum total cholesterol（TC）, triglyceride（TG）, and free fatty acid（FFA） were measured before operation and in 8 weeks after operation; plasma BUN and Cr were measured respectively before operation and in 4 and 8 weeks after operation in each group rats, 24 h urine microalbumin and urine 8-hydroxydeoxyguanosine were measured respectively before operation and in 8 weeks after operation in each group rats. Renal pathological changes were observed and the indexes of kidney hypertrophy, the mean glomerular area（MGA）, and the mean glomerular volume（MGV） were analyzed in 8 weeks after operation. The expressions of fibronectin, type Ⅳ collagen（CoⅣ）, transforming growth factor-β1（TGF-β1）, intercellular adhesion molecule-1（ICAM-1）, nicotinamide adenine dinucleotide phosphate oxidase 4（NOX4）, and Bcl-2 protein in renal tissues were investigated by immunohistochemical staining. Results Roux-en-Y gastric bypass surgery could reduce the blood glucose, blood lipid, MGA, MGV, and the index of kidney hypertrophy of diabetic rats significantly（P〈0.05）, improved renal pathological morphology and kidney function（P〈0.05）, reduced the protein expressions of fibronectin and CoⅣ, decreased the protein expressions of TGF-β1, ICAM-1, and NOX4,and increased the protein expression of Bcl-2. Conclusion Roux-en-Y gastric bypass surgery can improve kidney function and the pathologic

关 键 词：胃旁路术 糖尿病肾病 转化生长因子 NADPH氧化酶 细胞间黏附分子 BCL-2蛋白 

分 类 号：R587.2[医药卫生—内分泌] R656.61[医药卫生—内科学]