结肠黏膜Trx的表达与肠易激综合征发病机制的相关性研究

Correlation between Trx expression in colonic mucosa and pathogenesis of irritable bowel syndrome

目的观察硫氧还蛋白(Trx)在腹泻型肠易激综合征(IBS-D)和便秘型肠易激综合征(IBS-C)患者结肠黏膜中的表达情况,探讨肠易激综合征(IBS)的发病机制。方法选择2017年1月至2019年4月解放军总医院消化门诊收治的IBS-D、IBS-C患者各16例,分别设为IBS-D组和IBS-C组,另选择健康志愿者16例作为对照组,活检留取盲肠及乙状结肠黏膜组织,应用免疫组织化学染色分析。Western blot和荧光定量PCR法检测Trx及Trx mRNA表达情况。结果免疫组织化学染色显示,在正常结肠腺上皮细胞、隐窝上皮细胞、上皮基底膜和固有层间质细胞均可见Trx阳性表达。Western blot显示,Trx在IBS-D组和IBS-C组盲肠及乙状结肠的表达均明显高于对照组(P<0.05)。荧光定量PCR结果提示,与对照组比较,Trx mRNA在IBS-D组和IBS-C组盲肠黏膜的表达明显下调(P<0.05),在IBS-D组和IBS-C组乙状结肠黏膜的表达明显上调(P<0.01)。结论IBS发病机制可能与Trx相关的氧化应激、能量代谢异常及免疫稳态失衡相关。

Objective To investigate the expression of thioredoxin(Trx)in the colonic mucosa of patients with diarrhea-predominant irritable bowel syndrome(IBS-D)and constipation-predominant irritable bowel syndrome(IBS-C),and to explore the pathogenesis of irritable bowel syndrome(IBS).Methods From January 2017 to April 2019,16 patients with IBS-D and 16 patients with IBS-C in the gastroenterology department of PLA General Hospital were selected as the IBS-D group and the IBS-C group respectively,and 16 healthy volunteers were selected as the control group.The mucosal tissues of cecum and sigmoid colon were collected by biospy and analyzed by immunohistochemical staining,and the expression levels of Trx and Trx mRNA were observed by Western blot and fluorescence quantitative PCR.Results Immunohistochemical staining revealed positive Trx expression in normal colonic glandular epithelial cells,crypt epithelial cells,epithelial basement membrane,and stromal cells of lamina propria.Western blot showed that the expression levels of Trx in the cecum and sigmoid colon of the IBS-D group and the IBS-C group were significantly higher than those of the control group(P<0.05).According to the fluorescence quantitative PCR results,compared with the control group,Trx mRNA expression levels in the cecal mucosa of the IBS-D group and the IBS-C group were significantly down-regulated(P<0.05),while the expression levels of Trx mRNA in the sigmoid colon mucosa of the IBS-D group and the IBS-C group were significantly up-regulated(P<0.01).Conclusion The pathogenesis of IBS may be associated with Trx-related oxidative stress,abnormal energy metabolism,and immune homeostasis imbalance.