缬沙坦对糖尿病大鼠肾脏的保护作用

RENOPROTECTIVE EFFECTS OF VASATAN ON KIDNEY OF DIABETIC RATS

目的 :探讨血管肾张素 受体拮抗剂缬沙坦对糖尿病大鼠肾脏的保护作用。方法 :以一次性腹腔注射链脲佐菌素6 5 mg/kg,诱导建立糖尿病模型。将 30只大鼠分为正常对照组 (A组 )、糖尿病非干预治疗组 (B组 )及缬沙坦干预治疗组 (C组 )。1 2周后观察各组大鼠体重、血肌酐、尿素氮、血尿酸、血糖、2 4 h尿蛋白定量及肾脏病理改变。用免疫组化的方法观察肾组织中的纤维粘连蛋白、IV型胶原的沉积 ,以逆转录—巢式 PCR(RT- nested- PCR)法检测转化生长因子 -β(TGF-β1 )的表达。结果 :C组血肌酐、尿蛋白明显低于 B组 (P <0 .0 5 ) ,病理改变轻于 B组且未见有肾小球硬化。免疫组化示 C组肾组织中纤维粘连蛋白、IV型胶原的沉积明显少于 B组。 RT- nested- PCR法检测 C组 TGF-β1 m RNA的表达明显少于 B组。结论 :缬沙坦对糖尿病大鼠肾脏有明显的保护作用。其作用机制可能是通过减少尿蛋白 ,抑制 TGF-

Objective:To observe the renoprotective effect of angiotensin Ⅱ receptor antagonist Vasartan on the kidney of diabetic rats.Methods:Diabetic rats were induced by intraperitoneal Streptozotocin injection(65mg/kg) at one dose. The rats were divided into 3 groups:normal control(A),Vasartan untreated diabetic group(B) and Vasartan treated diabetic group(C). At the end of 12 weeks, body weight, creatinine, uria nitrogen, glucose, uric acid level of plasma and the urinary protein excretion were detected while renal tissues were examined routinely by light microscope. Furthermore,the protein expression of fibronectin(FN) and collagen IV, as well as that of transforming growth factorβ1 (TGF β1)were determined by immunohistochemistry and RT nested PCR respectively .Result:The level of serum creatinine and the proteinuria in Group C was significantly lower than that in Group B(P<0 05). The change of renal pathology in Group C is not serious as that of Group B and there was no hyalinization in glomeruli in the Group C. Immunohistochemistry staining indicated that there was an increasing FN and collagen IV deposition in Group B as compared to Group C while through the RT nested PCR,the significant increasing of the mRNA expression in TGF β1 was found in Group B ,which was much more higher than that of Group C.Conclusion:Vasartan has a definite protective effect on the kidney of diabetic rats and the decrease of proteinuria and the deposition of FN in the renal tissue ,which is probably due to its suppressive effect on the expressions of TGF β1, may be the mechanism for this action.