糖肾方对糖尿病肾病大鼠肾组织TGF-β_1及MMP-9表达的影响  

Effect of Tangshen Formula on Expression of TGF-β_1 and MMP-9 of Renal Tissue in STZ-induced Diabetic Nephropathy Rats

作　　者：张浩军[1] 李平[2] 赵静波 赵世萍[2] 严美花[1] 罗月会[1] 刘晖[2] 李克明[2] 杨丽平[1] 郭景珍[2] 

机构地区：[1]北京中医药大学,北京100029 [2]中日友好医院临床医学研究所,北京100029 [3]Mech-Sense,Aalborg Hospital Science & Innovation Center

出　　处：《中国中西医结合肾病杂志》2009年第4期290-294,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：国家重点基础研究发展计划("973计划")基金资助项目(No.2005CB523503);科技部国际科技合作计划基金资助项目(No.2006DFB31480);首都医学科技发展基金资助项目(No.2005-SF-Ⅰ-015)

摘　　要：目的:研究糖肾方对糖尿病肾病大鼠肾组织TGF-β1、MMP-2、MMP-9及Ⅳ型胶原表达的影响,探讨糖肾方对糖尿病肾病大鼠肾脏的保护机制。方法:50只Wistar大鼠随机分为空白组、模型组、蒙诺组(0.833mg/kg)、糖肾方大剂量组(2.67g/kg)、糖肾方小剂量组(1.33g/kg),每组10只,利用单侧肾切除加腹腔注射链脲佐菌素造成糖尿病肾病大鼠模型,连续给药20周。动态检测血糖和尿蛋白/肌酐水平;取肾组织进行病理组织学观察并对肾小球硬化和肾小管间质纤维化程度进行评分;RT-PCR方法检测TGF-β1、MMP-2及MMP-9mRNA表达,免疫组化方法检测肾组织TGF-β1及Ⅳ型胶原表达。结果:大剂量糖肾方能显著降低糖尿病肾病大鼠尿蛋白/肌酐(P<0.05),降低肾小球硬化指数(P<0.01)和肾小管间质纤维化指数(P<0.01),减少TGF-β1mRNA与蛋白表达(P<0.05),增加MMP-9mRNA表达(P<0.05),减少Ⅳ型胶原蛋白表达(P<0.05)。结论:糖肾方可减轻实验大鼠肾小球硬化和肾小管间质纤维化,其作用机制可能与抑制TGF-β1表达和提高MMP-9mRNA水平有关。Objective：To investigate the effect of Tangshen Formula （TSF） on expression of TGF-β1,MMP-2,MMP-9 and type Ⅳ collagen of renal tissue in STZ - induced diabetic nephropathy rats. Methods： Fifty Wistar rats were randomly divided in- to five groups：normal control, model control, model plus high-dose TSF （2.67 g/kg）, model plus low- dose TSF （ 1.33 g/kg） and model plus monopril （0. 833 mg/kg）, 10 rats in each group. The rat models were induced by right nephrectomy and peritoneal injec- tion of low- dosage streptozotocin （40 mg/kg）. The rats were sacrificed after 20 weeks of the insult. The blood glucose and urinary protein to creatinine ratio were dynamically tested. Renal pathological changes were observed and the indexes of glomerulosclerosis and renal interstitial fibrosis were analyzed using semi-quantitive image analysis method. The expressions of TGF-β1, MMP-2 and MMP-9 mRNA in renal tissue were examined using RT-PCR method. The expressions of TGF-β1 and type Ⅳ collagen an-tibodies were also immunohistochemically investigated. Results： Urinary protein to creatinine ratio （ P 〈 0.05）, and the indexes of glomerulosclerosis （P 〈 0.01）and renal interstitial fibrosis （ P 〈 0.01 ） were significantly improved in the high - dose TSF group. Furthermore,the high-dose TSF decreased expression of TGF-β1 protein, TGF-β1 mRNA and type Ⅳ collagen antibedies,and increased expression of MMP - 9 mRNA. Conclusion： High - dose TSF improved renal impairment on STZ - induced diabetic nephropathy rats. The one important mechanism of its effect is due to decreased accumulation of extraeellular matrix in the renal tissue through decreasing expression of TGF - β1 and increasing expression of MMP-9 mRNA.

关 键 词：糖肾方 糖尿病肾病 转化生长因子-Β1 基质金属蛋白酶 

分 类 号：R285.5[医药卫生—中药学]