辛伐他汀对糖尿病大鼠肾间质结缔组织生长因子和α-平滑肌肌动蛋白表达的影响  

Effects of simvastatin on expression of CTGF and α-SMA in renal tubulointerstitium of rats with diabetic nephropathy

作　　者：林斐莉[1] 沈汉超[1] 朱斌[1] 林开清[2] 

机构地区：[1]浙江大学医学院附属第二医院,浙江杭州310009 [2]浙江大学医学院附属妇产科医院,浙江杭州310006

出　　处：《浙江大学学报（医学版）》2010年第5期511-516,共6页Journal of Zhejiang University(Medical Sciences)

摘　　要：目的:探讨非降脂剂量的辛伐他汀对糖尿病大鼠肾间质结缔组织生长因子(CTGF)和α-平滑肌肌动蛋白(α-SMA)表达的影响。方法:60只雄性SD大鼠随机分为正常对照组(C组),糖尿病组(D组),糖尿病辛伐他汀干预组(DS组)。模型建立后,第6周及第12周时各组处死大鼠10只,称取体重、肾重,测定血糖(Glu)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、甘油三酯(TG)、肌酐(SCr),留取尿液测定24 h尿白蛋白排泄量(UAE),并用免疫组化方法检测肾间质结缔组织CTGF、α-SMA。结果:6周及12周时各组间SCr、LDL、HDL及TG相比无显著性差异(P>0.05);6周时DS组的肾间质CTGF、α-SMA表达水平明显少于D组(P<0.05),但与C组相比无显著性差异(P>0.05)。12周时DS组的肾间质CTGF、α-SMA表达水平明显少于D组(P<0.05),但高于C组(P<0.05)。结论:非降脂剂量的辛伐他汀可能通过抑制CTGF的表达和减少肾间质肌成纤维细胞的数量延缓肾小管间质纤维化进展。Objective： To investigate the effects of low-dose simvastatin on the expression of connective tissue growth factor（CTGF） and α-smooth muscle actin（α-SMA） in the renal tubulointerstitium of rats with diabetic nephropathy.Methods： Sixty male SD rats were randomly divided into three groups：Group C（control group）,Group D,in which diabetes was induced by stroptozotocin（STZ） and Group DS,in which STZ-induced diabetic rats were treated with low-dose（no cholesterol-lowering effect） simvastatin.The following parameters were measured after 6 weeks and 12 weeks in each groups,respectively： body weight and kidney weight,24-h urinary albumin excretion（UAE）,biochemical indexes including blood glucose（GLU）,low density lipoprotein（LDL）,high density lipoprotein（HDL）,triglycerides（TG）and serum creatinine（SCr）.The expression of CTGF and α-SMA in renal tubulointerstitium was assessed by immunohistochemical method.Results： After 6 and 12 weeks,there were no significant differences in SCr,LDL,HDL and TG levels among all three groups.The expression levels of CTGF and α-SMA in the tubulointerstitium of Group DS were significantly decreased compared with those of Group D at week 6（P0.05）;there were no significant differences compared with Group C（P0.05）.After 12 weeks,CTGF and α-SMA expressions in Group DS were also lower than those in Group D（P0.05）;while higher than those in Group C（P0.05）.Conclusion： Simvastatin with a under cholesterol-lowering dose,can decrease the expression levels of CTGF and α-SMA in renal tubulointerstitium of rats with diabetic nephropathy,by which the progression of the tubulointerstitial fibrosis would be delayed.

关 键 词：糖尿病 实验性 斯伐他汀/药理学 肌动蛋白类/代谢 胞间信号肽类和蛋白质类/生物合成 即早蛋白质类/生物合成 肾小球硬化症 病灶性/药物疗法 

分 类 号：R965[医药卫生—药理学]