【摘要】 研究水苏碱对肾纤维化大鼠肾组织CHOP、caspase-3作用的研究.采用单侧输尿管梗阻(UUO)诱导大鼠肾间质纤维化动物模型,以依那普利为阳性对照药,将大鼠随机分为假手术组、模型组、依那普利组、水苏碱高、中、低剂量组.术后第14 d处死大鼠,收集血清测定血肌酐(Scr)、尿素氮(BUN);采用HE染色检测肾小管损伤指数,Masson染色对肾间质胶原相对面积进行半定量分析;采用免疫组织化学方法检测肾组织中内质网应激特异转录因子(CHOP)、细胞凋亡因子天冬氨酸特异性半胱氨酸蛋白酶3(caspase-3)的表达.各治疗组与模型组比较大鼠肾小管间质损伤指数、肾间质纤维化程度、血清Scr、BUN水平及肾组织CHOP、caspase-3蛋白表达有差异(P<0.05;P<0.01).水苏碱与依那普利组比较,大鼠肾组织CHOP、caspase-3表达降低(P<0.05),肾小管间质损伤及肾间质纤维化程度明显降低(P<0.05),肾功能Scr、Bun明显降低(P<0.05).水苏碱可能通过下调内质网应激相关凋亡途径CHOP、caspase-3表达,干扰内质网应激特异转录因子的传导通路,抑制细胞凋亡的表达,从而减缓肾间质纤维化的发生和发展.更多还原

【Abstract】 This paper investigated the effect of stachydrine on the expression of CHOP( GADDl53) and caspase-3 in rats with renal interstitial fibrosis. Using unilateral ureter obstruction( UUO) to induce rats renal intersitital fibrosis animal models,with enalaprilat as the positive control. Rats were randomly divided into control group,model group,enalaprilat group,stachydrine high-dosage groups,stachydrine mid-dosage groups,stachydrine low-dosage groups. Rats were sacrificed after 14 days of operation. Blood were collected to determine serum creatinine( Scr) and urea nitrogen( BUN). The degree of the injury in nephridial tissue was evaluated by using HE; the degree of renal interstitial fibrosis was calculated by using Masson. The expression of CHOP and caspase-3 in renal tissue was examined by immunohistochemistry. Being compared with the enalaprilat group,expressions of CHOP and caspase-3 in the stachydrine group of high-dosage and mid-dosage were significantly decreased( P < 0. 05); the tubul damage index,renal interstitial fibrosis level, Scr and BUN representing renal function in high-dosage and mid-dosage stachydrinegroups were decreased obviously in comparison with those in the enalaprilat group( P < 0. 05). Stachydrine might slow down the occurrence and development of RIF by decreasing the expressions of ERS-related CHOP and caspase-3 to interfere in ERS-specific transcription factor pathway. The apoptosis was inhibited.更多还原