莫索尼定及福辛普利钠对阿霉素肾病肾组织TNF-α影响的对比研究

邹春波; 杜玄一; 解汝娟; 穆素红; 贾西贝; 李丽

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中国血液净化 ›› 2006, Vol. 5 ›› Issue (8) : 433-436.

基础研究

莫索尼定及福辛普利钠对阿霉素肾病肾组织TNF-α影响的对比研究

邹春波1 杜玄一2 解汝娟1 穆素红1 贾西贝1 李丽1

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摘要

目的探讨肿瘤坏死因子-α(TNF-α)及血小板源性生长因子-BB（PDGF-BB）在大鼠阿霉素肾病发病中的可能作用及对比研究莫索尼定及福辛普利钠对其影响。方法采用二次给药法尾静脉注射0.2%的盐酸阿霉素诱导肾病模型，随机等分3组（10只/组）：治疗组给予莫索尼定1.5mg/(Kg·d)或福辛普利钠10mg/(Kg·d)，肾病组给等量不含药物的食物丸；10只大鼠尾静脉注射等量生理盐水做为对照组。12周测血压、尿蛋白、血去甲肾上腺素（NE）、血管紧张素Ⅱ（AngⅡ）、TNF-α水平，肾组织行HE、Masson染色及电镜观察，免疫组化法测定肾组织TNF-α、PDGF-BB蛋白表达。结果肾病组24h蛋白尿、血生化指标、肾组织损伤形态学指标及TNF-α和PDGF-BB蛋白表达明显高于对照组（P＜0.01），两治疗组上述损伤指标轻于肾病组（P ＜0.01）。结论 TNF-α及PDGF-BB在ADR肾组织内高表达，可能参与肾组织损伤，莫索尼定及福辛普利钠可能通过下调TNF-α及PDGF-B蛋白表达而起肾保护作用。

Abstract

Objective To study the role of tumor necrosis factor-α(TNF-α) and platelet deviced growth factor-BB (PDGF-BB) in the pathogenesis of adriamycin-induced nephropathy and the effects and moxonidine or monopril on them. Method Rats were received twice-intravenous injection of adriamycin and divided into nephropathy group(NEP)、moxonidine treatment group (for a dose of 1.5 mg/(kg·d) and monopril treatment group [10 mg/(kg·d)]；10 healthy rats were as control group. At the end of the experiment,the proteinuria and nonepinephrine (NE)、angiotensin Ⅱ(AngⅡ) and TNF-α in blood were detected.Kidey damage were evaluated by quantitative histology.The protein expression of TNF-α and PDGF-BB were determined by immunohistochemical staining. Results Compared with control group,proteinuria and the levels of NE、AngⅡ and TNF-α in the blood were increased(P＜0.01),the expression of TNF-α and PDGF-BB in renal tissue were all significantly up-regulated(P＜0.01) in adrianycin induced nephropathy rats.After the treatment of moxonidine and monopril, related parameters were all inhibited(P＜0.01). Conclusion Increased expression of TNF-α and PDGF-BB protein may play an important role in the progression of kidney disease,moxonidine and monopril can protect kidney by down-regulating the expression of TNF-αand PDGF-BB.