依普利酮抑制细胞增殖拮抗急性环孢素A肾损伤的研究

目的探讨盐皮质激素受体阻断剂依普利酮抑制细胞增殖拮抗环孢素A肾损伤的作用。方法经口灌服环孢素A(100 mg.kg-1.d-1),诱导小鼠急性肾脏损伤,给以依普利酮100 mg.kg-1.d-1治疗,d 10采血、摘取肾脏。放免法检测血清醛固酮水平,免疫组化检测增殖细胞核抗原(PC-NA)、纤连蛋白表达;RT-PCR、Western blot检测PCNA、FN、TGF-β1表达。结果血清醛固酮水平检测显示环孢素A组(318.83±95.72)ng.L-1较空白对照组(82.05±23.04)ng.L-1升高,依普利酮可明显抑制其分泌(149.50±36.20)ng.L-1。环孢素A组肾脏PCNA阳性细胞增多,纤连蛋白表达增强;PCNA、FN、TGF-β1蛋白及mRNA表达较空白对照组明显上调,依普利酮可抑制其表达。结论依普利酮可以抑制醛固酮的分泌、抑制细胞增殖,减轻环孢素A诱导的肾脏损伤。

Inhibitory effect of eplerenone on cell proliferation in acute cyclosporine nephrotoxicity

Aim To investigate the inhibitory effect of mineralocorticoid receptor blocked eplerenone on cell proliferation in acute cyclosporine nephrotoxicity.Methods Acute cyclosporine nephrotoxicity in mice was induced by cyclosporine A(CsA) with 100 mg·kg-1·d-1 orally and treated with eplerenone 100 mg·kg-1·d-1.The blood and kidneys were harvested on the 10th day.Serum aldosterone was detected with radioimmunoassay.Proliferaion cell nuclear antigen(PCNA) and fibronectin(FN) were measured with immunohistochemistry.PCNA,FN and TGF-β1 weredetected with RT-PCR and western bolt.Results Aldosterone level in blood was increased in CsA treated mice(318.83±95.72)ng·L-1 than that in control mice(82.05±23.04)ng·L-1 and inhibited by eplerenone(149.50±36.20)ng·L-1.PCNA positive cells and FN increased in CsA group with immunohistochemistry.Expression of PCNA,FN and TGF-β1 were up-regulated in CsA treated mice by RT-PCR and western blot and down-regulated by eplerenone.Couclusion Eplerenone has the role of reducing secretion of aldosterone,inhibiting the cell proliferation thus reducing the renal damage induced by CsA.