苯那普利对糖尿病肾小球细胞外基质增生的抑制作用及机制

BENAZEPRIL DECREASED THE ACCUMULATION OF GLOMERLAR EXTRACELLULAR MATRIX IN DIABETIC RAT

目的 :了解血管转换酶抑制剂苯那普利对单侧肾切除糖尿病大鼠肾脏结构和功能改变的保护作用及机制。 方法 :应用生物化学分析 ,RT- PCR方法检测苯那普利治疗对糖尿病大鼠血尿素氮、肌肝、血脂、肾小球细胞外基质 (ECM)以及肾皮质内金属蛋白酶 - 3(MMP- 3)的m RNA表达的影响。 结果 :糖尿病大鼠的尿素氮、肌酐及甘油三酯、胆固醇水平均较非糖尿病大鼠明显增加 ,PAS染色发现肾小球系膜区 ECM明显积聚。苯那普利治疗后肾功能指标、甘油三酯水平明显下降 ,升高的胆固醇也有下降趋势 ,ECM积聚显著被抑制 ,苯那普利治疗组大鼠肾皮质内金属蛋白酶 3m RNA表达明显增加。 结论 :单侧肾切除加重了糖尿病大鼠的肾脏病变 ,苯那普利治疗可通过多种途径发挥显著的防治作用 ;其中对组织学改变的保护作用可能与其上调金属蛋白酶的表达 ,促进 ECM降解密切相关。

OBJECTIVE To investigate the effects of benazeprol treatment on the accumulation of glomerual extracellular matrix(ECM) and the expression of metalloproteinase in uninephrectomized rats(Unx)with diabetes. METHODOLOGY 30 male SD rats were uninephrectomized two weeks before the extablishment of diabetes.Diabetes were induced by the bouns injection of STZ(65mg/kg).The diabetic rats were randomly divided into the benazeprol treated( n =10)and untreated group( n =10)and were followed up for 4 weeks.After sacrifice,renal histology was studied and the levels of metalloproteinase 3(MMP 3)mRNA expression in diabetic kidney was measured by the semi quantitative reverse transcription polymerase chain reaction. RESULTS In the untreated group,significant increases of blood glucose(BG),BUN,Scr,trigly ceride(TG)and cholesterol(Cho)were observed.Between the treated and untreated groups,no significant difference of BG level was found.While BUN and serum creatinine levels were decreased of 21 3% and 9 6% respectively in the treated group,compared to the untreated group.A decrease of serum TG and Cho were also found in the treated group.In the study of the pathology of the reminant kidney of diabetic rats,marked golmerular ECM accumulation and mesangial expansion were observed.The expression of MMP 3 mRNA was found very low in the renal cortex of Unx and it further declined in diabetic rats(0 82 times control level).Benazepril treatment attenuated the accumulation of EMC observed in diabetic rats.Interestingly,Benazepril treatment significantly increased renal MMP 3 mRNA levels,which were 3,4 fold of untreated diabetic rats. CONCLUSION Benazepril effectively delays and retards the development and progression of diabetic nephropathy by decreasing ECM accumulation.The effect of benazepril on ECM accumualtion is due to its modulation of MMP expression.