中药芪红合剂对肾间质纤维化模型大鼠肾组织中PAI-1表达的影响

The effect of Astragalus and Safflower mixture on expression of tissue inhibitors of motalloprotenase in renal tubulointerstitial fibrosis in rats with Unilateral Ureteral Obstruction

目的:探讨中药芪红合剂对肾间质纤维化模型大鼠肾组织中纤溶酶原激活物抑制剂-1(PAI-1)表达的影响,及其对肾间质纤维化的作用机制。方法:采用单侧输尿管结扎(UUO)致肾间质纤维化的动物模型,40只雄性Wistar大鼠随机分为4组:假手术组(A组)、手术模型组(B组)、芪红合剂组(C组)、依那普利组(D组)。术后14d处死各组大鼠,收集血清、测定血肌酐(Scr)、尿素氮(BUN)水平,取结扎侧肾组织分别用HE、Masson染色,采用免疫组化检测肾组织中纤溶酶原激活物抑制剂-1(PAI-1)的表达,并用计算机图像分析系统进行分析。结果:模型组大鼠肾组织中PAI-1的表达较假手术组显著升高,两治疗组较模型组明显降低。模型组大鼠血肌酐、尿素氮水平较假手术组明显增高,两治疗组较模型组显著下降。结论:中药芪红合剂可降低大鼠血尿素氮、血肌酐水平,并可通过抑制纤溶酶原激活物抑制剂-1(PAI-1)的表达,而起到减轻肾间质纤维化病变程度的作用,推测其抑制PAI-1表达上调的作用可能是其抗肾间质纤维化的作用机制之一。

Objective： To observe the effect of Astragalus and Safflower mixture on the expression of PAI-1 in rats with Unilatreal Ureteral Obstruction. To investigate the theraputic effects and its mechanisms of Astragalus and Safflower mixture. Methods： Rat renal interstitial fibrosis model was produced by unilateral ureteral obstruction,dO Wistar male rats were randomly divided into four groups： sham group（A group）,UUO group（B group）, A＆S group（C group） and ACEI group（D group）. Sera and kidney tissues were collected from each group on the forteenth day.Bun and Scr were measured.h was carried out to measure the level of tubulointerstitial damage by Masson staining. The expression of PAI-1 in kidneys was analyzed by immunohistochemical method. Results： The expression of PAI-1 and the renal interstitial fibrotic area were highter significantly than that in sham group. Compared with UUO group, those of the treatment groups decreased markedly. The level of BUN and Scr in UUO group were significantly highter than that in sham group.Compared with UUO group,the level of BUN and Scr in treatment groups were significantly lower. Conclusion： Astragalus and Safflower mixture can downregulate the level of BUN and Scr in UUO animal model rats, Astragalus and Safflower mixture can suppress the upregulation of PAI-1 expression in kidneys of UUO animal model rats and decrease their interstitial fibrotic area.It is inferred that it may be one of the mechanisms of Astragalus and Safflower mixture suppressing renal tubular damage and interstitial fibrosis.