The Effects Of Benazepril On Thrombomoduline And Plasminogen Activator Inhibitor-1 In Diabetic Rats With Renal Lesions

Objective:To explore the effects of Benazepril on Thrombomoduline and plasminogen activator inhibitor-1 in diabetic rats with renal lesions,and the mechanism of its protecting the kidney.Method:72 Wistar rats were divided randomly into three groups:normal control group,diabetic group,and treated with benazepril group.The subjects in diabetic group and treated with benazepril group were injected intraperitoneally with dose streptozotocin(STZ,50mg/kg) while the ones in normal control group were injected intraperitoneally with the similar dose of citrate buffer.Benazepril(10 mg.kg-1.d-1) was given to the treated with benazepril group,whereas the same milliliter distilled water was given to the other two groups.At the end of 4,8 and 12 weeks,weight,fast Blood glucose,fast blood insulin and 24-hour urinary protein were observed, serum TM,PAI-1 were measured,the pathological changes of kidney were examined using light microscope and electron microscope.Results:1.There was a difference in the level of blood glucose between the control group and the other two groups(P＜0.01).The difference was significant after injected intraperitoneally with STZ and the level of blood glucose was not less than 16.7mmol/L in diabetic group and treated with benazepril group.2.Compared with normal control group,there were significant differences in the level of fast blood glucose,fast blood insulin and C-peptide(P＜0.01) in diabetic group and C,the former was higher than norm,and the latter two were lower than it(P＜0.01).The differences between them had existed for the whole course of the experiment.3.Compared with the control group,diabetic group and treated with benazepril group have expressed more urinary albumin excretion since the fourth week(P＜0.01).The levels of urinary albumin excretion(UAE) increased gradually from the fourth to the twelfth week(P＜0.01);Compared with diabetic group,treated with benazepril group had an decrease of UAE respectively at every stage(P＜0.01),and UAE of treated with benazepril group was no obviously increas from the fourth to the twelfth week(P＞0.05).4.Pathohistological study revealed that there was more glomerular matrix and thicker glomerular basement membrane in diabetic group than treated with benazepril group.With the progress of disease,the difference in renal pathohistological between with two groups was significant(P＜0.05,P＜0.01).5.The levels of TM,PAI-1 of diabetic group and treated with benazepril group was much higher than normal control group(P＜0.01),and increased continually during the whole experiment.Treated with benazepril group had lower level of TM,PAI-1 than diabetic group at every stage.The relationgship between TM with PAI-1,TM and PAI-1 with UAE is positive correlation in diabetic group and treated with benazepril group(P＜0.01).Conclusion:1.The levels of plasma TM,PAI-1 increased continually during the whole disease course in diabetic rats with renal lesions.It indicated that TM and PAI-1 could respectivly reflect the function of endothelial cell,inhibit fibrinolysis,both of whose disorder resulted in the occurrence of diabetes with renal lesions.During the progess of it,there was the positive correlationship between TM and PAI-1.So they maybe play the cooperative role in this progress.2.Treated with benazepril group had lower level of UAE,TM and PAI-1 respectively at every stage than diabetic group.It meant benazepril could contribute to decrease proteinuri,inhibit TM and PAI-1 generating,and delay the disease course.Benazepril has some protective effect on renal functions in diabetes,which may relate wih the inhibition to glomerular sclerosis by down-regulating TM and PAI-1 in blood plasma.