褐藻多糖硫酸酯对腺嘌呤致大鼠肾间质纤维化的干预作用及其机制探讨

Effect of Fucoidan on Renal Interstitial Fibrosis in Adenine-Induced Chronic Renal Failure in Rats

目的:观察褐藻多糖硫酸酯(FPS)对大鼠慢性肾衰竭模型肾间质纤维化的干预作用,并初步探讨其机制。方法:将Wistar雄性大鼠随机分为3组,即:(1)正常对照组(n=15);(2)CRF模型组(n=24),进食含0.75%腺嘌呤的饲料;(3)CRF+FPS治疗组(n=24),在进食含0.75%腺嘌呤饲料的同时每天给予FPS 200mg.kg-1.d-1灌胃。持续喂养6周。于第2、4、6周末收集大鼠血、尿标本,应用自动分析仪测定血肌酐、白蛋白和24h尿蛋白;并留取肾组织,Masson染色切片分析肾间质纤维化程度,免疫组化方法半定量分析肾组织中α平滑肌肌动蛋白(α-SMA)的表达。结果:CRF+FPS治疗组大鼠24h尿蛋白均明显低于同期CRF模型组(P<0.05),白蛋白水平6周时明显高于CRF模型组(P<0.01),但两组间血肌酐水平无统计学差异(P>0.05)。CRF+FPS治疗组大鼠肾组织Masson染色间质纤维化指数评分也明显低于同期CRF模型组(P<0.01),该肾组织α-SMA蛋白表达2、4、6周均明显低于同期CRF模型组(P<0.05)。结论:FPS治疗可以减少腺嘌呤致肾衰竭大鼠的尿蛋白排泄,减轻肾间质纤维化程度,其机制可能与抑制肾小管上皮细胞-间充质细胞转化有关。

Objective：To examine the effect of fucoidan on renal interstitial fibrosis in the adenine- induced chronic renal failure in rats. Methods： Male Wistar rats were divided into three groups： normal group （ n = 15 ）, CRF group （ n = 24 ）, CRF ＋ FPS group （ n = 24）. CRF rats were fed with foocl containing 0.75 % adenine. CRF ＋ FPS rats were fed with foocl containing 0.75 % adenine as well as FPS 200 mg·kg- 1· d- 1 by intragastric administration. The rats were respectively sacrified at the end of the 2th, 4th and 6th weeks. The bloocl and 24 hour urine were collected for biochemical analysis including serum creatinine, albumin and urinary protein. The renal tissue was harvested for pathological study. Masson stain of renal tissue was performed to grade the extent of renal interstitial fibrosis. Expressions of α- smooth muscle actin（ α- SMA） was detected by immunohistological method. Results： The level of urinary protein in CRF＋ FPS group was evidently lower than that in CRF group, and the level of bloocl albumin in CRF＋ FPS group was higher than that in CRF group at the last week. However, serum creatinine level was not significantly different from that in CRF rats. Furthermore, interstitial and tubular histopathological changes were lessened in FPS- treated rats. The expression of α- SMA in renal tissue was significantly lower in CRF ＋ FPS group compared with that in the CRF group. Conclusion： FPS may reduce proteinuria and ameliorate renal fibrosis in adenine- induced chronic renal failure of the rats. This effect is probably related to its suppression of epithelial- mesenchymal transition （EMT） of renal tissue.