曲尼司特对环孢素A致慢性肾毒性大鼠骨形成蛋白、转化生长因子β1表达的影响

Influence of tranilast on expression of BMP-7,TGF-β1 in rats with chronic cyclosporin A nephrotoxicity

目的观察曲尼司特对环孢素A(CsA)慢性肾毒性大鼠模型肾脏病理改变和BMP-7、TGF-β1表达的影响,以探讨曲尼司特防护CsA慢性肾毒性的可能机制。方法给进低盐饮食SD大鼠灌胃20 mg·kg-1·d-1剂量的CsA制作大鼠CsA肾毒性模型,同时以400 mg·kg-1·d-1剂量的曲尼司特喂饲以预防肾毒性,以10 mg·kg-1·d-1剂量的伊贝沙坦作对照,于治疗第4周测定有关指标。结果曲尼司特能明显减少肾小管上皮细胞空泡变性和细胞坏死,减少间质炎细胞浸润及间质纤维化,免疫组化显示TGF-β1表达下调, BMP-7表达增加,两者呈负相关(P<0．05)。结论曲尼司特能减少TGF-β1表达,增加BMP-7表达,减轻CsA所致的慢性肾脏病理变化。

Objective To evaluate influence of tranilast on protein expreasion of BMP-7,TGF-β1 in rats with chronic cyclosporin A nephrotoxicity and explore the mechanisms of protective effect of it. Methods CsA was administered to SD rats on low salt diet by gastric garage at a dose of 20mg/kg once daily for 28 days. Tranilast（in a dose of 400mg/kg once daily） were gave to prevent nephrotoxicity and irbesartan（in a dose of 10mg/kg once daily） were used to these rats as control. The related targets were observed at 4 weeks after therapy. Results Tranilast attenuated tubular cells vacuolations as well as interstitial damage including inflammatory cells infiltration and focal interstitial fibrosis. Meanwhile, tranilast down-regulated the expression of TGF-β1 and up-regulated the expression of BMP-7 in kidney. There was negative correlation between the two. Conclusion Tranilast can decrease the expression of TGF-β1 and up-regulation the expression of BMP-7,which can auenuate the structural changes of kidney in chronic CsA nephrotoxicity rats.