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.