雷公藤甲素治疗db／db糖尿病小鼠的疗效观察  

Triptolide ameliorates proteinuria and improves renal lesion in diabetic db/db mice

作　　者：高清[1] 刘志红[2] 秦卫松[2] 郑春霞[2] 张明超[2] 曾彩虹[2] 王生余[2] 王建平[2] 朱晓东[2] 黎磊石[2] 

机构地区：[1]南京大学医学院临床学院博士研究生 [2]南京军区南京总医院解放军肾脏病研究所,南京210002

出　　处：《肾脏病与透析肾移植杂志》2009年第6期519-528,共10页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：全军“十一五”重点课题(06G040);南京军区“十一五”重点课题(06Z35)

摘　　要：目的:利用db/db小鼠验证雷公藤甲素对糖尿病肾脏损伤的治疗作用,探讨雷公藤甲素防治糖尿病肾病的机制。方法:9周龄的db/db和db/m小鼠分为五组:(1)db/m正常对照组;(2)db/db糖尿病对照组;(3)缬沙坦治疗组;(4)雷公藤甲素低剂量治疗组;(5)雷公藤甲素高剂量治疗组。于4周、8周及12周测定各组24h尿白蛋白、血生化和体重。光镜观察肾小球病变,电镜观察足突改变,并作定量分析。免疫病理观察足细胞裂孔膜蛋白nephrin,足细胞损伤标志物desmin,炎症反应标志物单核细胞趋化蛋白1(MCP-1),氧化应激标志物4羟壬烯醛(4-HNE)的表达。结果:db/db小鼠经雷公藤甲素治疗后蛋白尿下降,肾小球肥大和足细胞损伤减轻,肾组织炎症和氧化应激状态改善,同时高血脂和肥胖减轻。该作用随治疗时间延长,效果更加明显,且高剂量疗效优于低剂量。雷公藤甲素降低蛋白尿、改善肾小球肥大的作用与缬沙坦相似,但降低肾组织炎症和氧化应激的作用雷公藤甲素比缬沙坦更强。结论:雷公藤甲素能明显降低db/db小鼠尿蛋白的排泄,减轻肾组织炎症反应,改善肾脏组织病变,对糖尿病肾脏损伤具有显著且更全面的治疗作用。Objective：To investigate the effects and mechanisms of triptolide on renal lesions in db/db with mice diabetic nephropathy, nethodology：db/db and db/m mice with 9-wks of age were divided into five groups： group A, db/m mice were treated with saline; group B, db/db mice with saline; group C, db/db mice with valsatan [ 20 mg/（kg.d） ] ; group D and E, db/db ,nice with triptolide [25 μg/（kg.d） and 50μg/（kg.d） 1. The body weight, levels of plasma glucose, plasma lipids, and 24-h urinary albumin excretion were measured every 4 weeks. The morphological changes of renal tissue, imnmnofluorescence and immunohistology of nephrin, desmin, MCP-I and 4-HNE were detected in all groups. Results：The level of urinary albumin excretion, glomerular area, Glomerular/Bowman＇s capsule volume ratio （%） , and foot process width were decreased in triptolide group. The podocyte density in triptohde group was higher than that in db/db control group. The expressions of nephrin, desmin, MCP-1 and 4-HNE were significantly improved by triptolide. The plasma levels of cholesterol, triglyeeride, low density lipoprotein and high density lipoprotein were also improved by triptolide treatment. Those effects of triptolide were dose and time dependent. Triptolide had the similar effects on ameliorating albuminuria and glomerular hypertrophy, and more powerful effects on ameliorating inflammation and oxidative stress in renal tissue. Conclusion：Triptolide had significant and general renoprotective effects on db/db mice with diabetic nephropathy, which may be related with mneliorating albuminuria, relieving inflammation and improving renal lesion by triptolide.

关 键 词：雷公藤甲素 缬沙坦 DB/DB糖尿病小鼠 糖尿病 蛋白尿 

分 类 号：R285.5[医药卫生—中药学]