氯沙坦对糖尿病肾病大鼠肾小球硬化的影响  

The Effect of losartan on glomerular sclerosis in rats with diabetic nephropathy

作　　者：许军英[1] 陶立坚[1] 王菱[1] 宁旺斌[1] 刘纪实[2] 

机构地区：[1]中南大学湘雅医院肾内科,长沙410008 [2]中南大学湘雅三医院肾内科,长沙4100013

出　　处：《中南大学学报（医学版）》2008年第9期836-840,共5页Journal of Central South University ：Medical Science

摘　　要：目的:探讨氯沙坦对糖尿病肾病大鼠细胞外基质降解作用的机制。方法:采用链脲霉素(streptozotozin,STZ)诱导的糖尿病肾病大鼠模型,将大鼠随机分为正常组、模型组和氯沙坦组,16周后测血肌酐、尿素氮。对肾组织进行HE和Masson染色,计算肾小球硬化指数。Western免疫印迹测定肾脏Ⅳ型胶原和结缔组织生长因子(connective tissue growth factor,CTGF)的蛋白表达量,real time-PCR方法检测肾组织Ⅳ型胶原mRNA,转化生长因子-β(transforming growth factor-β,TGF-β)mRNA和CTGFmRNA的表达水平。结果:氯沙坦组血尿素氮、肾小球硬化指数及肾组织Ⅳ型胶原、CTGF蛋白表达均低于模型组(均P<0.05);Ⅳ型胶原mRNA,TGF-β1mRNA及CTGFmRNA的表达水平均低于模型组(均P<0.05)。结论:氯沙坦可能通过抑制TGF-β1和CTGF,减少Ⅳ型胶原积聚,减轻肾小球硬化。Objective To explore the degradation mechanism of losartan on extracellular matrix in rats with diabetic nephropathy. Methods The rat model of diabetic nephropathy was established by streptozotozin （STZ） injection, and the rats were randomly divided into 3 groups： （a normal group, a model group and a losartan group）. For 16 weeks, the serum creatinine and urea nitrogen were measured, and glomerular sclerosis index （GSI） were caculated. The expression of collagen Type Ⅳ, eonnective tissue growth factor and transforming growth factor-β1 were examined by Western blot and real time-PCR respectively. Results Blood urea nitrogen, GSI and the expressions of collagen Type Ⅳ and CTGF protein in the losartan group were lower than those in the model group （ all P 〈 0. 05 ） , and the expressions of collagen Type Ⅳ mRNA, TGF-β1 mRNA and CTGF mRNA were lower than those in the model group （ all P 〈0. 05 ）. Conclusion Losartan modulates glomerular sclerosis and decreases the accumulation of collagen Type Ⅳ by inhibiting TGF-β1 and CTGF.

关 键 词：肾小球硬化 氯沙坦 Ⅳ型胶原 转化生长因子-Β1 结缔组织生长因子 

分 类 号：R692[医药卫生—泌尿科学]