安体舒通联合西拉普利对糖尿病大鼠肾脏保护作用的研究

Renal protective effect of spirinolactone and cilazapril on diabetic rats

目的:探讨安体舒通和西拉普利联合使用对糖尿病大鼠肾脏的保护机制。方法:Wistar大鼠随机分为5组:对照组(N组);模型组(D组);安体舒通组(S组);西拉普利组(C组);联合给药组(S+C组)。采用链脲佐菌素(STZ)注射于单肾切除大鼠的腹腔中建立糖尿病肾脏损害大鼠模型。4周后观察大鼠的24h尿微量白蛋白及血清肌酐清除率。免疫组化法检测肾切片中核因子-κB(NF-κB)及纤溶酶原激活物抑制剂-1(PAI-1)的表达。用逆转录聚合酶链式反应(RT-PCR)方法检测肾组织中血管紧张素Ⅱ-1型受体(AT-1R)的表达。结果:各给药组均可抑制糖尿病大鼠24h尿微量白蛋白的增加、血清肌酐清除率的降低及肾组织病理结构损害,联合组优于单独给药组。各给药组均可抑制肾组织NF-κB及PAI-1的表达,以联合组最明显。各给药组均可使AT-1RmRNA的表达减少,以联合组最明显。结论:安体舒通与西拉普利联合用药对糖尿病肾脏保护作用优于单独用药,其部分机制可能是通过抑制NF-κB及PAI-1的活化、减少AT-1R表达而实现的。

AIM： To assess the renal protective effect of the combination use of spirinolactone and cilazapril on streptozotocin（STZ）-induced diabetic rats with single nephrectomy. METHODS： Diabetic nephropathies were induced by intraperitoneal injection of STZ in the rats with single nephrectomy. The rats were randomly divided into 5 groups： normal control; diabetes; diabetes treated with spirinolactone; diabetes treated with cilazapril; diabetic rats treated with spirinolactone and cilazapril. The expression of NF-κB and PAI-1 in the glomeruli was detected by immunohistochemical staining. RT-PCR was performed to evaluate the mRNA expression of AT-1R. RESULTS： Increased 24 h urinary protein, decreased Ccr and the pathological injury of the renal tissues were improved by the treatment with either spirinolactone or cilazapril alone and further ameliorated by using the combination of the two drugs. The activity of NF-κB and PAI-1 was higher in the renal tissues of diabetic rats than that in control group, and further attenuated by the combination therapy in both cases （P〈0.05）. The over-expression of AT-1R mRNA observed in the diabetic rats was attenuated by treating with spirinolactone or cilazapril and further reduced by the combination use of the two drugs （P〈0.05）.CONCLUSION： The combination use of spirinolactone and cilazapril confers superiority over monotherapy on the effect of renal protection. The mechanism may be partly correlated with synergistic suppression of the increasing activity of NF-κB and PAI-1 as well as the over-expression of AT-1R mRNA in renal tissues.