阿魏酸哌嗪对环孢素A慢性肾毒性大鼠肾脏的保护作用

The effect of piperazine ferulate on the kidney of the rats with chronic cydosporine A nephrotoxidty

目的探讨不同剂量阿魏酸哌嗪（PF）对环孢素A（CsA）慢性。肾毒性大鼠肾脏TGF-β／Smads通路的影响。方法采用低盐饮食加CsA20mg·kg^-1·d^-1灌胃的方法建立环孢素A慢性肾毒性肾脏模型。雄性SD大鼠24只，随机分为正常对照组（N）、模型组（M）、PF低剂量治疗组（P1）、PF高剂量治疗组（P2）。第4周末肾组织行HE染色观察肾组织病理学变化；免疫组织化学和RT-PCR技术检测不同剂量PF对大鼠肾脏TGF-β1、Smad3、Smad7的影响。结果PF能下调CsA慢性肾毒性大鼠肾组织中TGF-β1、Smad3及其mRNA水平的表达，上调Smad7及其mRNA水平的表达。结论PF可能通过下调TGF-β1、Smad3，上调Smad7来发挥其防治CsA慢性肾毒性的作用。

Objective To investigate the effect of Piperazine ferulate （PF）on TGF-β/Smads pathway in rats with chronic cyclosporine A（CsA） nephrotoxicity. Methods 24 SD rats were on low salt diet, and CsA was administered by gastric gavage at the dose of 20 mg·kg^-1· d^-1 for 28 days. They were randomly divided into 4 groups： Normal control group （group N）; Model control group （group M）; Low-dose treatment group of PF（group P1）; High dose treatment group of PF（group P2）. At the end of 4th week, the renal morphology was observed; TGFβ1, Smad3 and Smad7 were detected by semi-quantitative RT-PCR and imrnunohistochemistry methods. Results Morphologically, kidneys in group M exhibited significantly more fibrosis, interstitial damage, which was blunted by PF. The protein and mRNA levels of TGFβ1 and Smad3 in the kidneys in treatment group were significantly lower than in group M. Like irbesartan, PF decreased the level of TGF-β1 and Smad3 in a dosedependent manner. In addition, PF increased the renal expression of Smad7 in rats with chronic CsA nephrotoxicity. Conclusions PF showed a renal protective effect on chronic CsA nephrotoxicity of rat models by decreasing the level of TGFβ1 and Smad3 and increasing the level of Smad7.