缬沙坦对糖尿病肾病大鼠肾间质纤维化的作用  

Effect of valsartan on renal interstitial fibrosis in diabetic nephropathy rats

作　　者：唐琳[1] 易润[1] 杨冰[1] 李慧[1] 陈慧娟[1] 王刘伟[1] 刘章锁[1] 

机构地区：[1]郑州大学第一附属医院肾内科郑州大学肾脏病研究所,450052

出　　处：《中华肾脏病杂志》2012年第8期633-638,共6页Chinese Journal of Nephrology

基　　金：河南省高等学校青年骨干教师资助计划（2010GGJS-004）

摘　　要：目的探讨缬沙坦在防治糖尿病肾病（DN）大鼠肾间质纤维化（RIF）中的作用及其机制。方法54只大鼠随机被分为对照组（c组）、DN模型组（D组）和缬沙坦治疗组（T组）。D组和T组大鼠分别给予链脲菌素（STZ）一次性腹腔注射建立糖尿病大鼠模型。造模后T组给予缬沙坦混悬液40mg·kg-1·d-1，分别于实验第4周、第8周和第12周末测血糖、血浆白蛋白、Scr、尿蛋白。Masson染色观察RIF面积。免疫组化法检查肾组织缺氧诱导因子1d（HIF-1α）、金属蛋白酶1组织抑制剂（TIMP-1）、基质金属蛋白酶9（MMP．9）的表达。实时荧光定量PCR测定其mRNA表达。结果与C组比较，D组及T组大鼠24h尿蛋白量、Scr均显著升高，肾组织RIF面积、HIF-1α、TIMP-1蛋白及mRNA表达均显著增加，血清白蛋白及肾组织中MMP-9蛋白及其mRNA表达均明显减少，差异均有统计学意义（均P〈0．05）。与同时间点D组比较，T组在实验第8周末、第12周末24h尿蛋白、Scr均显著降低，肾组织中RIF面积、HIF-1α、TIMP-1蛋白及其mRNA表达均显著减少，血清白蛋白及肾组织中MMP-9及其mRNA表达均显著增多，差异均有统计学意义（均P〈0．05）。结论缬沙坦可能通过下调HIF-1α、TIMP—1表达，上调MMP-9表达，延缓肾间质纤维化。Objective To investigate the effect of valsartan on expression of HIF-1α, TIMP-1, MMP-9 in the process of renal interstitial fibrosis（RIF） in diabetic nephropathy（DN） rats. Methods Fifty-four SD rats were randomly divided to 3 groups： control group （group C）, DN group （group D）, valsartan treatment group （group T）. Rats of group D and T were given streptozocin （STZ） by intraperitoneal injection to establish animal model of diabetes. After diabetic models were successfully made, rats of group T were treated by valsartan （40 mg kg-1 d-1）. Serum glucose, serum creatinine and urinary protein were measured at the 4th, 8th and 12th weeks. Masson staining was used to calculate the area of RIF. The methods of immunohistochemistry and real-time PCR were used to detect the expressions of HIF-1α, TIMP-1, MMP-9 in renal interstitium. Results Compared with group C, the areas of RIF were larger, 24-hour urinary protein, Scr were higher, the mRNA and protein expression of HIF-1α and TIMP-1 increased, while the mRNA and protein expression of MMP-9 decreased in D and T group （P〈0.05）. At the 8th, 12th weeks, compared with group D, the areas of RIF were smaller, 24-hour urinary protein, Scr were relatively lower expressions of HIF-1α and TIMP-1 decreased, while the eapressions of MMP-9 increased in group T （P〈0.05）. Conclusion Valsartan may delay the progress of RIF in DN rats by down-regulating the expressions of HIF-1α, TIMP-1, up-regulating the expression of MMP-9, then improve renal function.

关 键 词：糖尿病肾病 纤维化 缺氧诱导因子1 Α亚基 金属蛋白酶1组织抑制剂 基质金属蛋白酶9 缬沙坦 

分 类 号：R285.5[医药卫生—中药学]