阿魏酸哌嗪对阿霉素肾病大鼠肾脏保护作用的探讨

Renoprotective Effects of Piperazine Ferulate on Rats Nephrotic Syndrome

目的 :探讨阿魏酸哌嗪对阿霉素肾病大鼠的肾脏保护作用及其可能机制。方法 :采用阿霉素静脉注射建立阿霉素肾病模型 ,设阿霉素肾病未治疗组 ,阿魏酸哌嗪治疗组 ,福辛普利治疗组及正常对照组 ,8周后观察阿魏酸哌嗪对 2 4h尿蛋白量、肾功能、血脂及肾脏病理影响 ,应用免疫组化测定肾组织标本FN、Ⅳ型胶原、TGF - β1、PAI - 1、ET - 1的表达 ,RT -PCR测定TGF - β1、PAI - 1的mRNA表达。结果 :阿魏酸哌嗪可减少阿霉素肾病大鼠尿蛋白排出量 ,明显降低甘油三酯 ,减少TGF - β1、PAI- 1、FN、Ⅳ型胶原、ET - 1表达 ,作用与福辛普利相似。结论 :阿魏酸哌嗪能减轻阿霉素肾病大鼠的肾脏损害 ,对肾脏具有保护作用。

Objective:To investigate the effects and mechanism of piperazine ferulate on adriamycin-induced nephrotic syndrome in rats.Methods:Nephrotic syndrome was induced by intravenous injection of ADR.Rats were divided into 4 groups:untreated nephrotic group(NS group),nephrotic group treated by piperazine ferulate(P group),nephrotic group treated by fosinopril(F group)and normal control group(NC group).The P and F groups were given piperazine ferulate 50 mg·kg -1·d -1 and fosinopril 25 mg·kg -1·d -1 by gavage for 8 weeks,respectively,while NS and NC group were given with water only.Urinary protein excretion,BUN,serum creatinine,blood cholesterol and triglyceride were measured at the end of the study.Renal pathological changes were evaluated and immunohistochemistry was used to examine the expression of fibronectin(FN),collagen Ⅳ,transforming growth factor β 1(TGF-β 1),plasminogen activator inhibitor 1(PAI-1)and endothelin-1(ET-1).RT-PCR was used to examine the TGF-β 1 mRNA and PAI-1 mRNA in the cortex of the kidney.Results:Compared with the untreated nephrotic syndrome rats,proteinuria and triglyceride of rats treated piperazime ferulate were significantly reduced (P<0.01).Immunohistochemistry analysis showed piperazine ferulate can decrease the expression of fibronectin,type Ⅳ collagen,transforming growth factor β 1,plasminogen activator inhibitor 1(P<0.05)and endothelin-1(P<0.01)in the kidney.RT-PCR showed piperazine ferulate decreased the over-expressions of TGF-β 1 and PAI-1 mRNA.Similar results were observed in fosinopril treated rats.Conclusion:Piperazine ferulate mitigate damage of adriamycin nephropathy by decreasing extracellular matrix accumulation and inhibiting TGF-β 1 and PAI-1 expression in kidney of rats.