PERK-eIF2a通路在IBS-D肠黏膜屏障中的作用及痛泻要方体内代谢后“成分群”的干预机制

肠易激综合征腹泻型（IBS-D）严重影响患者的健康和生活质量。肠上皮细胞过度应激（ERS）激活PERK-eIF2a通路可能是损害肠道黏膜屏障，导致IBS-D发生的重要发病机制。痛泻要方治疗IBS-D在临床上取得了较好的疗效，但其作用机制不明。本项目以痛泻要方为研究对象，考察其在人体的代谢情况，通过药物代谢组学手段，将内源药效标志物与药效药理指标相结合，经肝肠循环后血浆中的代谢物分析，确定体内“多重起效”的药效成分（群），同时采用病证结合模型大鼠对其相关作用机制进行研究，揭示痛泻要方的可能作用机制，为中药复方的基础研究提供新的思路，为进一步的临床应用提供指导。

Diarrhea irritable bowel syndrome(IBS-D）has seriously affected health and quality of life of patients.It may be important pathogenesis in development and recurrence of the process of IBS-D,excessive reticulum stress (ERS)activated PERK-eIF2α pathway and damaged intestinal mucosal epithelial Barrier.Tongxieyaofang(TXYF) had obtained satisfactory effect in treating IBS-D in clinic and previous study, but it is unknown that herbal fomula how to work.This project applys metabonomics method to detect plasma metabolites for patients after treatment, rat model combined syndrome with disease, using molecular biology research methods to explore the function of ERS inducing damage in IEC and probable pathological mechanism,and to determine the effects of the”multiple ingredients “of TXYFin the body.