贝那普利和厄贝沙坦对糖尿病肾病肾组织表达KLK1的影响

Influences of Benazepril and Irbesartan on Kallikrein 1 Expression in Rat Kidneys with Diabetes Nephropathy

目的探讨贝那普利和厄贝沙坦阻断肾素-血管紧张肽系统(RAS)对糖尿病肾病(DN)肾组织表达激肽释放酶1(KLK1)的影响。方法将10只雄性SD大鼠以普通饲料喂养,作为正常对照组(A组)。将雄性SD大鼠以高糖高脂饮食加小剂量链脲佐菌素诱导DN模型,造模成功后随机分为4组,每组10只:DN组(B组)、贝那普利干预组(C组)、厄贝沙坦干预组(D组)、贝那普利联用厄贝沙坦干预组(E组)。干预8周后测定肾质量/体质量、24 h尿蛋白与血肌酐、尿素氮等评估肾功能情况,免疫组化半定量测定肾组织KLK1蛋白表达水平。结果 B、C、D、E组大鼠肾组织表达KLK1蛋白水平显著高于A组(P<0.01);C、D、E组大鼠肾组织表达KLK1蛋白水平显著高于B组(P<0.05);E组表达KLK1高于C组和D组(P<0.01);C组和D组差异无统计学意义。结论 DN大鼠肾组织表达KLK1蛋白高于正常大鼠,贝那普利和厄贝沙坦通过阻断RAS上调肾脏KLK1蛋白表达。

Objective To investigate the effect of renin-angiotension system blocking on kallikrein 1 （KLK1） expression in rat kidneys with diabetes nephropathy. Methods Sixty male SD rats were injected with low dosage streptozotocin and fed with high fat and sucrose diets to establish a diabetes nephropathy （DN） model. Then the DN animals were randomly divided into five groups,ten rats in each group,as normal controls （group A） ,diabetic nephropathy model （group B） ,benazepril treatment （ group C）, irbesartan treatment （ group D）, benazepril combined irbesartan groups （ group E）. The rats were sacrificed after 8 weeks. The kidney weight/body weight ,24-hours proteinuria, serum creatinine and urea nitrogen were measured to evaluate renal function. KLK1 was stained by immunohistochemical （IHC）technique in kidneys. Results It was demonstrated that the expression level of KLK1 in group B, C, D, E were significantly higher than that in group A（P〈0.01 ）. Compared with the group B,the expression of KLK1 in group C, D,E were increased （P〈0.05）. Compared with the group C and group D,the KLK1 expression level was elevated in group E （P〈0.05）. There was no significant difference between the group C and D （P〉0.05）. Conclusion It is suggested that benazepril and irbesartan may increase the expression of KLK1 in renal tissues of DN rats by blocking RAS.