摘要
目的研究曲尼司特对阿霉素肾病大鼠的肾脏保护作用,并探讨其可能的机制。方法雄性SD大鼠24只,随机分为正常对照组、模型组、曲尼司特组和安博维组。采用单侧肾脏切除加尾静脉注射阿霉素5mg/kg的方法建立阿霉素肾病模型。观察各组大鼠24h尿蛋白定量、BUN、Scr及肾脏病理的影响。应用免疫组化方法测定肾组织CTGF和TGF-β1的表达。结果曲尼司特能减少阿霉素肾病大鼠尿蛋白,延缓Scr上升;减轻基质增生和肾小球硬化;曲尼司特下调阿霉素肾病大鼠肾组织中CTGF和TGF-β1的表达。结论曲尼司特下调阿霉素肾病大鼠肾组织中CTGF和TGF-β1的表达,调节细胞外基质的生成与降解,从而减轻肾脏病理损害,发挥其肾脏保护作用。
Objective To investigate the effects and mechanism of tranilast on adriamycin-induced nephrotic syndrome in rats. Methods Twenty-four rats were randomly divided into 4 groups： normal control group, model control group, irbesartan treatment group, tranilast treatment group. The rats in normal control group were injected with normal saline via the tail vein. The rats in the other groups were uninephrectomized and injected with adriamycin 5 mg/kg via the tail vein one week later. Rats in model group received sodium carboxymethycellulose via gavage. Rats in irbesartan treatment group received irbesartan 10mg/kg·d via gavage. Rats in tranilast treatment group received tranilast 400 mg/kg via gavage. All rats were sacrificed at the end of week 8. The body weight, 24 hours urinary protein, BUN, and Scr were measured at the end of the study. Renal pathological changes were evaluated and immunohistochemistry was used to examine the expression of CTGF and TGF-β1. Results Compared with the untreated nephrotic syndrome rats, proteinuria and Scr in rats treated with tranilast were significantly reduced （P〈0. 05）. Compared with model group, the renal pathological change was decreased and glomerular sclerosis was markedly lower in tranilast treatment groups. Immunohistochemstry analysis showed that tranilast could decrease the expression of CTGF and TGF-β1 in the kidney of rats with adriamycin nephropathy. Conclusion Tranilast can effectively decrease Scr, urine protein, and relieve glomeruluspathologic injury of adriamycin nephropathy rats. Tranilast has a renoprotective effect on adriamycin-induced nephrotic syndrome in rats. The mechanism may be related to that tranilast can depress the expression of CTGF and TGF-β1 in the kidney, as a result, it can decrease the synthesis and secretion of extracellular matrix.
出处
《西部医学》
2008年第2期242-244,248,共4页
Medical Journal of West China
关键词
曲尼司特
阿霉素肾病
结缔组织生长因子
转化生长因子Β1
Tranilast
Adriamycin nephropathy
Connective tissue growth factor
Transforming growth factor-β1
