Toll样受体4在褐藻多糖硫酸酯干预治疗大鼠肾间质纤维化中的作用

Effects of Toll-like Receptor 4 Expression on Treatment of Renal Interstitial Fibrosis by Fucoidan Polysaccharide Sulfate in Rats

目的:探讨Toll样受体4(TLR4)在大鼠肾间质纤维化(RIF)中的表达情况及褐藻多糖硫酸酯(FPS)干预治疗对其调节作用。方法:将54只大鼠随机分为假手术组、模型组和药物组,每组18只,模型组和药物组制作单侧输尿管梗阻(UUO)模型,分别于术后2、4、6周处死大鼠,观察大鼠血肌酐(Scr)、尿素氮(BUN)及肾组织病理改变,并应用免疫组织化学方法检测肾组织TLR4及核因子(NF)-κB的表达。结果:假手术组大鼠肾组织TLR4及NF-κB无表达或仅有轻度表达;与假手术组相比,模型组肾组织表现为纤维化病理改变,同时TLR4及NF-κB强阳性表达(P<0.05),并随病程延长及纤维化的进展表达呈上升趋势;与模型组相比,药物组TLR4及NF-κB的表达减少(P<0.05),有效降低了Scr、BUN,减轻了肾间质纤维化程度。结论:褐藻多糖硫酸酯可能通过调节TLR4的表达而减缓肾纤维化病程进展。

Objective：To observed the Toll-like receptor 4 （TLR4） expression in the process of renal interstitial fibrosis （RIF）,and therapeutic effect of fucoidan polysaccharide sulfate （FPS） thereof.Methods：Fifty-four rats were randomly divided into three groups,sham operation （SOR）group,unilateral ureteral ligation obstruction model group （UUO） and FPS treatment group （FPS）.Rats were sacrificed in batches and specimens were collected at 2,4 and 6 weeks after operation.The levels of serum creatinine （Scr）,blood urea nitrogen （BUN） and HE stain were observed.The expressions of TLR4 and NF-κB in renal tissues were detected by immunohistochemical method.Results：There were no expressions or only slight expression of TLR4 and NF-κB in kidneys of SOR group.The renal fibrosis was found,and positive expressions of TLR4 and NF-κB in UUO group compared with those of SOR group （P 0.05）.The expressions of TLR4 and NF-κB were gradually increased with extension of obstruction and the progress of the renal fibrosis.The expressions of TLR4 and NF-κB were decreased in FPS group than those of UUO group （P 0.05）,which decreased levels of Scr,BUN and renal fibrosis.Conclusion：FBS alleviated renal fibrosis by regulating the expression of TLR4.