摘要
目的:探讨血府逐瘀胶囊对单侧输尿管梗阻所致大鼠肾间质纤维化的作用及其机制。方法:雄性SD大鼠随机分为假手术组、模型组、血府逐瘀胶囊治疗组,采用单侧输尿管结扎术(UUO)建立大鼠肾间质纤维化模型。术后21d取各组大鼠肾组织HE染色及六胺银染色(PASM),观察肾组织病理变化;检测大鼠血肌酐和尿素氮含量,观察肾功能变化;放射免疫法检测肾组织中Ⅲ型前胶原含量,观察肾纤维化程度;Western blot检测肾组织中核转录共抑制因子SnoN与Ski蛋白表达水平,观察TGF-β1/Smad信号转导通路中逆向调控信号分子表达水平的变化。结果:与假手术组比较,模型组大鼠肾小管基底膜明显增厚,部分肾小管上皮细胞变性,肾小管萎缩,管腔显著扩张,肾间质明显增宽;血肌酐与尿素氮含量以及肾组织中Ⅲ型前胶原含量显著增加;SnoN、Ski蛋白表达显著减少。血府逐瘀胶囊治疗组大鼠梗阻侧肾组织的病理变化明显改善,血肌酐与尿素氮水平以及肾组织中Ⅲ型前胶原含量明显降低,SnoN蛋白表达水平显著增加,而Ski蛋白表达没有改变。结论:血府逐瘀胶囊可通过恢复SnoN蛋白表达水平,抑制TGF-β1靶基因的活化,从而改善UUO大鼠的肾功能和肾间质纤维化程度。
Objectlve：To study the effects of ＂Xuefu Zhuyu Capsule＂ on renal interstitial fibrosis induced by unilateral ureteral obstruction in rats and its mechanisms. Methods： The male SD rats were randomly divided into three groups： sham-operated group, model group and ＂Xuefu Zhuyu Capsule＂ group. Model of renal interstitial fibrosisi was established by unilateral ureteral obstruction（UUO） in rats. All rats were sacrificed on 21st day operation and the obstructed renal tissues were stained with HE and PASM respectively. The level of serum ereatinine （Scr） and blood urea nitrogen （BUN） were assayed with the kits to determine the renal function and the contents of procollagen m N-terminal peptide in total tissue homogenates of the obstructed kidney were measured with radioimmunoassay to observe the fibrosis of kidney. Protein expression levels of the nuclear transcriptional corepressors SnoN and Ski in the kidney were analyzed with Western blotting. Results：Compared with sham-operated group, the rats＇ kidney in model group presented a series of change, such as the tubular basement membrane thickening, parts of tubular epithelial cell degenerating, renal tubule atrophying and lumens expanding, tubular interstitium broadening. The levels of Set and BUN and contents of procollagen Ⅲ N-terminal peptide were more higher and the expression of SnoN and Ski proteins were significantly lower than those in the sham-operated group. In the ＂Xuefu Zhuyu Capsule＂ group, the amelioration in pathological lesion of the obstructed kidney was evident. The level of Scr, BUN and contents of procollagen Ⅲ Nterminal peptide decreased significantly. The expression of SnoN increased significantly, while there was no significant change in the expression of Ski. Conclusion： ＂Xuefu Zhuyu Capsule＂ can improve the kidney function and block the progression of renal interstitial fibrosis in UUO rats by restoring the expression of SnoN and inhibiting activation of TGF-β1 target gene.
出处
《上海中医药大学学报》
CAS
2008年第6期35-38,共4页
Academic Journal of Shanghai University of Traditional Chinese Medicine
基金
上海市教委科研基金资助项目(06cz015)
国家自然科学基金资助项目(30500687)
上海市教委重点学科建设资助项目(J50301)
关键词
血府逐瘀胶囊
肾间质纤维化
核转录共抑制因子
＂Xuefu Zhuyu Capsule＂
renal interstitial fibrosis
nuclear transcriptional corepressor
