罗格列酮对2型糖尿病大鼠血浆resistin的影响及对肾小球硬化的干预研究  

Effect of rosiglitazone on serum resistin and glomerular sclerosis in type 2 diabetic rats

作　　者：牟娇[1] 贾德福 何作云[3] 高凌云[3] 叶自林[1] 袁发焕[1] 

机构地区：[1]第三军医大学新桥医院肾内科,重庆400037 [2]重庆警备区门诊部,重庆400010 [3]第三军医大学新桥医院心内科,重庆400037

出　　处：《中国病理生理杂志》2009年第8期1635-1639,共5页Chinese Journal of Pathophysiology

基　　金：重庆市自然科学基金资助项目(No.2006BB5074)

摘　　要：目的:研究罗格列酮对糖尿病大鼠血清巨噬细胞因子resistin水平的影响,探讨该药物对糖尿病肾小球硬化的干预及可能的作用机制。方法:20只10周龄Wistar大鼠随机分为糖尿病肾病(DN)模型组和罗格列酮干预组(DN+RSG),另取10只Wistar大鼠作为正常对照组(NC)。DN和罗格列酮干预组大鼠右肾切除后经过阴茎背静脉注射35mg/kg链脲菌素(STZ),罗格列酮组按照10mg.kg-1.d-1的剂量给予罗格列酮灌胃,DN组及正常对照组喂饲普通饮食。STZ注射20周后留取静脉血和24h尿,后处死大鼠并取肾组织。ELISA法检测血浆白细胞介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)及resistin水平,免疫比浊法测定高敏C反应蛋白(hs-CRP),并测定24h尿微量白蛋白、空腹血糖及肾功能水平。光镜下观察肾组织的病理改变情况,免疫组化检测肾小球转化生长因子-β1(TGF-β1)的表达,Westernblotting检测Smad2磷酸化水平。结果:与NC组比较,DN组大鼠血浆炎症因子IL-1、TNF-α、hs-CRP及resistin的水平均显著升高;罗格列酮干预后血浆中上述指标含量均显著低于模型组。与DN组比较,罗格列酮干预组的空腹血糖无明显变化,但24h尿微量白蛋白定量及肾功能水平均明显下降。罗格列酮干预后肾小球内TGF-β1蛋白表达及Smad2磷酸化水平较DN组显著降低,并且其肾小球系膜增生程度也较DN组明显减轻。结论:罗格列酮具有延缓及改善糖尿病肾小球硬化的作用,该作用可能与其降低re-sistin及其它炎症相关因子的表达有关。针对炎症有望控制DN的发生发展。AIM： To observe the effect of rosiglitazone on serum resistin level and to investigate the possible mechanism of glomerular sclerosis in type 2 diabetic rats. METHODS ： Ten - week - old Wistar rats were divided into diabetic nephropathy （DN） group （ 10 cases） and DN ＋ rosiglitazone group （ 10 cases）. The other 10 Wistar rats were used as normal control group. Type 2 diabetic rats were induced by cutting the right kidney and injecting small dose （35 mg/kg） of streptozocin （STZ）. Rosiglitazone group received rosiglitazone 10 mg ·kg^-1·d^-1 while normal control group and DN group were fed with normal chow diet. After 20 weeks, vessel blood was collected for plasma IL - 1, TNF -α and resistin assayed by ELISA. The serum levels of glucose, creatinine, urea nitrogen and microalbum of 24 h urine were also detected. The expression of TGF - β1 in glomerulus was examined by immunohistochemistry. Smad2 phosphatase activity was detected by Western blotting. RESULTS ： The plasma IL - 1, TNF - α, hs - CRP and resistin, and microalbum of 24 h urine in rosiglitazone group, were significantly lower than those in DN group while the serum level of glucose was not different from that in DN group. The expression of TGF - β1 and phosphorylated level of Smad2 were lower in rosiglitazone group than those in DN group. The degree of glomerular sclerosis in rosiglitazone group was obviously lighter than that in DN group. CONCLUSION ： Rosiglitazone delays and ameliorates the development of diabetic glomerular sclerosis. The mechanism is possibly related to the modulation of resistin and other inflammatory factors. Anti - inflammation is a potential way for controlling diabetic nephropathy.

关 键 词：罗格列酮 抵抗素 转化生长因子Β 糖尿病肾病 

分 类 号：R363[医药卫生—病理学]