阿魏酸哌嗪对环孢霉素A慢性肾毒性的影响

目的：探讨阿魏酸哌嗪对环孢霉素A（CsA）慢性肾毒性的保护作用。方法：按四组分别给予实验大鼠橄榄油，CsA，CsA加低剂量阿魏酸哌嗪50mg／（kg·d）]及CsA加高剂量阿魏酸哌嗪100mg／（kg·d）]，四周后取血测血肌酐，计算肌酐清除率，取肾组织测定肾组织和血中的血管紧张素Ⅱ浓度，同时作肾组织病理学检查。通过免疫组化观察肾组织内皮素及Ⅲ型胶原表达情况。结果：CsA大鼠肾脏可见明显损伤，同时肌酐清除率明显下降，血浆及肾组织血管紧张素Ⅱ含量增高，而且肾组织局部内皮素及Ⅲ型胶原表达明显增高。给予阿魏酸哌嗪能使肾损伤有所减轻，使血液及肾组织血管紧张素Ⅱ含量减少，内皮素及Ⅲ型胶原表达下降。结论：CsA引起慢性肾毒性可能与血管紧张素Ⅱ、内皮素和Ⅲ型胶原增加有关，同时应用阿魏酸哌嗪可以使血浆及肾脏组织血管紧张素Ⅱ减少，内皮素和Ⅲ型胶原表达下降，因此对肾脏有保护作用，而且这种作用与剂量有相关性。

Protective Effects of Piperazine Ferulate on Cyclosporine-induced Chronic Nephrotoxicity in Rats

Objective： To investigate the mechanism of the protective effects of piperazine ferulate （PF） on cyclosporine-induced chronic nephrotoxicity in rats. Methods： Twenty-four SD rats in 4 groups were respectively treated with olive oil 2 mL/（kg · d）, cyclosporin A （CsA） 20 mg/（kg · d）, CsA 20 mg/（kg · d） plus PF 50 mg/（kg ·d）, CsA plus PF 100 mg/（kg·d）. At the end of 4 weeks of treatment, all the rats were sacrificed and blood was analyzed for serum creatinine and creatinine clearance（Ccr）, and kidney tissue for pathologic analysis. The content of angioten sin Ⅱ （Ang Ⅱ ） in serum and renal tissue were measured. The expression of endothelin-1 （ET-1） and collagen protein- Ⅲ （COLL-Ⅲ） was evaluated by immunohistochemistry. Results： Severe renal damage was significant in cyclosporine-induced rats and Ccr also was decreased. In the CsA-treated group, there was a significant increase in the level of Ang Ⅱ in serum and renal tissue. Simutaneously, the expression of ET-1 and COLL-Ⅲ of this group was significantly higher. PF minimized effects of CsA on kidney function. The values of the parameters mentioned above were improved. Conclusion： The damage of kidney induced by CsA might be mediated by over-expression of Ang Ⅱ , ET-1 and COLL-Ⅲ. PF could prevent these effects and protected the kidney, and this effect is related with the dose of PF.