辛伐他汀保护糖尿病大鼠肾损害及对肾组织MCP-1表达的影响  

Simvastain's renoprotection effects and its influence on MCP-1mRNA expression of renal tissue in STZ-induced diabetic rats

作　　者：郑茂[1] 叶山东[1] 杨光伟[1] 李秀财[1] 陈燕[2] 范爱红[2] 王迎新[3] 陈柯[4] 

机构地区：[1]安徽医科大学附属省立医院安徽省立医院内分泌科,安徽合肥230001 [2]安徽省立医院内分泌实验室,安徽合肥230001 [3]安徽医学高等专科学校药理教研室,安徽合肥230601 [4]安徽省立医院病理科,安徽合肥230001

出　　处：《中国实验诊断学》2008年第6期695-698,共4页Chinese Journal of Laboratory Diagnosis

基　　金：安徽省教育厅自然科学研究资助项目(2006KJ318B);安徽省自然科学基金资助项目(070413255X)

摘　　要：目的观察辛伐他汀对糖尿病大鼠肾脏组织的保护作用及其对尿单核细胞趋化蛋白-1(UMCP-1)排泄和肾组织MCP-1mRNA表达的影响。方法将Wistar大鼠随机分为正常对照(C组,n=8)、糖尿病组(D组,n=8)、辛伐他汀治疗组(S组,n=8)。糖尿病大鼠模型建立一周后,S组以辛伐他汀(20 mg.kg-1.d-1)灌胃,D组和C组灌以相应量的生理盐水。第2,4,8周检测各组大鼠尾外周血糖,第8周时测12小时尿白蛋白排泄率(UAER)、尿视黄醇结合蛋白(URBP)和UMCP-1排泄率,处死大鼠留取肾脏标本用于病理学检查及逆转录聚合酶链反应(RT-PCR)。结果①与C组比较,D、S组第2,4,8周血糖及糖化血红蛋白(HbA1c)水平较明显升高,而后两组间差异无统计学意义;②第8周,D,S组UAER及URBP、UMCP-1排泄率和肾脏肥大指数均高于C组(P<0.01),S组上述四项指标较D组明显降低(P<0.01),UMCP-1排泄率与UAER、URBP排泄率及肾脏肥大指数呈正相关;③电镜下S组肾小球病变较D组明显减轻,同C组相比仅有少量病变;④与C组相比,D组大鼠肾脏MCP-1mRNA表达明显上调(P<0.01),S组MCP-1mRNA表达也增加(P<0.05)但明显低于D组(P<0.05)。结论辛伐他汀对糖尿病大鼠肾脏有确切保护作用,其机制可能部分与抑制肾脏MCP-1过度表达有关。Objective To investigate the renoprotective effects of simvastain and its influence on the expression of MCP-1mRNA in kidney tissue and urinary MCP-1 excretion of diabetic rats. Methods 24 Wistar Rats were assigned to normal control group （group C, n = 8）, SIZ-induced diabetes mellitus group （group D, n = 8） and simvastain （20 mg.kg^-1 .d^-1） treatment group（group S, n = 8） .The peripheral blood glucose was measured at the 2nd,4th and 8th week and HbAlc was assessed at the 8 th week.At the 8 th week, the urinary excretion rates of albumin （ALB）, retinal-binding protein （RBP） and monocyte chemoattractant protein- 1 （ MCP- 1 ） were tested and relative kidney index was calculated. The renal tissues of diabetic rots were obtained for RT-PCR to examine the gene expression of MCP-1 in renal tissue.Results ①The blood glucose levels at the 2nd,4th and 8th week and HbAlc at the 8th week in groups D and S were significant higher than those in group C at the same period（ P 〈 0.01 ） ;②At the 8 th week, not only the urinary excretion rates of ALB,RBP and MCP-1 ,but also the relative kidney index were markedly increased in groups D and S compared with group C（ P 〈 0.01）. However, the parameters above in group S were much lower than those in group D （ P 〈 0.01 ）. In addition, the urinary excretion of MCP-1 was positively correlated to the urinary ALB excretion, the urinary RBP excretion and relative kidney index;③Pathological changes observed by electron microscope of group S were much lighter than those of group D,but a little heavier than those of group C;④ In comparison with group C,the expression of MCP-1mRNA was significantly up-regulated in group D and group S; the expression of MCP-1 mRNA in group S was reduced markedly compared with that in group D（ P 〈 0.05）. Conclusion Simvastain has renoprotective effects through down-regulating the over-expression of MCP-1 mRNA in renal tissue and reducing urinary excretion of MCP-1 in STZ-induced diabetic rats.

关 键 词：糖尿病 糖尿病肾病 单核细胞趋化蛋白-1 辛伐他汀 HMG-COA还原酶抑制剂 

分 类 号：R587.2[医药卫生—内分泌]