辛伐他汀对大鼠肾小管上皮细胞转分化的作用

目的:观察辛伐他汀对实验性1型糖尿病大鼠肾小管上皮细胞转分化的作用。方法:将实验动物随机分为对照组、糖尿病组及治疗组。治疗组给予辛伐他汀[5 mg/(kg.d)]治疗12周。于实验第6,9,12周检测24 h尿蛋白(24 h TP),12周检测血清肌酐(Scr),内生肌酐清除率(Ccr)和NAG酶。采用免疫组织化学技术检测各组肾小管间质中-αSMA,MCP-1,CD44表达水平。结果:糖尿病大鼠肾组织中-αSMA,MCP-1和CD44表达较对照组明显增加(P<0.01),治疗12周后,辛伐他汀可明显降低1型糖尿病肾病大鼠肾小管间质中-αSMA,MCP-1和CD44表达(P<0.01),并降低蛋白尿(P<0.01),改善肾功能各指标及肾组织病理学损害。-αSMA表达分别与MCP-1,CD44表达及24 hTP呈正相关(r=0.998 5,0.976 3,1.000 0,P<0.01)。结论:辛伐他汀对糖尿病肾小管间质病变具有保护作用,其机制至少部分与抑制肾小管上皮细胞转分化,下调肾小管间质中-αSMA,MCP-1和CD44表达有关。

Inhibition of Transdifferentiation of Renal Tubular Epithelial Cells by Simvastatin in Rats

Objective: To investigate the effects of simvastatin on the renal tubular epithelial myofibroblast transdifferentiation in type 1 diabetic rat.Methods: Male Wistar rats were randomly divided into three groups as the control group,type 1 diabetic group and type 1 diabetic rats treated with simvastatin(5 mg/).After six,nine and twelve weeks,urinary protein was measured.After twelve weeks,β-N-acetyglocosamidase,endogenous creatinine clearance rate and serum creatinine were measured respectively.The expressions of α-smooth muscle actin(α-SMA),monocyte chemoattractant protein-1(MCP-1) and homing cell adhesion molecule(CD44) were assayed by immunohistochemistry.Results: Compared with those of the control group,the expressions of α-SMA,MCP-1 and CD44 increased in tubulointerstitium of the rats in diabetic group(all P<(0.01).) After 12 weeks of therapy,simvastatin down-regulated significantly the expressions of(α-SMA) and MCP-1 CD44(P<0.01),lowered urine protein(P<0.01),and improved the renal function and the renal tissue injury.The expressions of α-SMA was positively correlated with the expressions of MCP-1 and CD44,and urinary protein(r=0.998 5,0.976 3,1.000 0,all P<(0.01).) Conclusion: Simvastatin can prevent tubulointerstitium damage in progressive diabetic kidney disease.The mechanism may be associated,at least in part,with inhibiting renal tubular epithelial myofibroblast transdifferentiation,and down-regulating α-SMA,MCP-1 and CD44 expressions in tubulointerstitium in type 1 diabetic rats.