PDIA3在腹泻型肠易激综合征患者结肠黏膜中的蛋白表达及其意义

摘要

Background: The mechanisms of irritable bowel syndrome (IBS) remain unclear yet, and visceral hypersensitivity is considered as one of its main pathophysiological mechanisms. Protein disulfide isomerase A3 (PDIA3) is overexpressed in colonic mucosa in rats with visceral hypersensitivity. However, the protein expression and significance of PDIA3 in colonic mucosa of patients with irritable bowel syndrome with diarrhea (IBS-D) are not clear. Aims: To investigate the protein expression and mechanism of PDIA3 in colonic mucosa of patients with IBS-D. Methods: Fifteen IBS-D patients met Rome Ⅲ diagnostic criteria and 15 healthy controls were included in this study. Western blotting was used to determine the protein expression of PDIA3 in colonic mucosa, and concentration of tryptase in colonic mucosa cultured supernatant was determined by ELISA. Results: Compared with controls, protein expression of PDIA3 was up-regulated in colonic mucosa in IBS-D patients (P＜0.01), tryptase concentration was significantly increased (P＜0.01). The concentration of tryptase was positively correlated with the protein expression of PDIA3 in patients with IBS-D (r=0.750, P=0.003).Conclusions: PDIA3 may promote the release of tryptase that causes visceral hypersensitivity, and thereby PDIA3 may be involved in the pathogenesis of IBS-D.%肠易激综合征(IBS)的发病机制尚未完全明了,内脏敏感性增高是其主要的病理生理基础之一.研究显示蛋白质二硫键异构酶A3(PDIA3)在内脏高敏感大鼠结肠黏膜组织中高表达,但其在腹泻型IBS(IBS-D)患者结肠黏膜中的蛋白表达及其意义尚不清楚.目的:探讨PDIA3在IBS-D患者结肠黏膜中的蛋白表达及其作用机制.方法:收集符合罗马Ⅲ诊断标准的15例IBS-D患者和15例健康对照者.采用蛋白质印迹法检测结肠黏膜PDIA3蛋白表达,ELISA法检测结肠黏膜孵育上清液类胰蛋白酶浓度.结果:与对照组相比,IBS-D患者结肠黏膜中PDIA3蛋白表达明显上调,类胰蛋白酶浓度明显升高,差异均有统计学意义(P＜0.01).IBS-D患者类胰蛋白酶浓度与PDIA3蛋白表达呈正相关(r=0.750.P=-0.003).结论:PDIA3可能通过促进类胰蛋白酶释放,导致内脏敏感性增高,从而在IBS-D的发病机制中起重要作用.