俞募配穴针刺改善肠道动力障碍的ICC自噬失衡调控机制

As the most common disease, slow transmission constipation (STC) affects people's physical and mental health. Recent studies have shown that excessive autophagy in the colon of interstitial cells of Cajal(ICC) is the important pathological factor contributing to STC. In previous studies, we found that the efficacy of needling at back Shu and front Mu points of Meridian of Large Intestine for treating functional constipation has close relationship with colon autophagy. However, the specific mechanism of acupuncture remains unclear. Therefore, this study targets STC, choose the imbalance of intestinal ICC autophagy as a breakthrough point, to research on the mechanism of acupuncture at Shu-Mu points of Large Intestine Meridian for treating STC. We hypothesis that needling the back Shu and front Mu points of STC rat model can balance the autophagy of ICC and improve the intestinal motility. We use immunofluorescence, Western Blot, focus on the protein expressions of PI3K-Akt-mTOR signal pathway, which is a classical pathway of autophagy, and other autophagy protein, such as Beclin1、LC3, as well as the changes of gastric emptying rate, small intestinal propulsion rate, colon tissue morphology, ultrastructure of colon ICC to answer our hypothesis. Above all, this experiment is designed to explore the partial efficacious mechanism of needing the back Shu and front Mu of Large Intestine Meridian for treating in order to provide evidences for the clinical application of acupuncture treatment of STC.

慢传输型便秘（STC）是影响人们身心健康的重要常见病、多发病。最新研究表明，结肠ICC过度自噬是导致STC的重要病理环节。在前期研究中，我们发现针刺俞募穴对功能性便秘的治疗效应可能与自噬有关，但其具体途径尚不清晰。因此，本项目以针灸治疗优势病种——STC为研究对象，以肠道ICC自噬失衡为切入点，围绕“针刺俞募穴对STC的治疗效应与调控ICC自噬平衡、改善肠动力有关”这一假说，采用免疫荧光、Western Blot等技术方法，以自噬经典途径—PI3K-Akt-mTOR信号通路相关蛋白及自噬相关蛋白Beclin1、LC3的表达为主要观察指标，结合胃排空率、小肠推进率、结肠组织形态、结肠ICC超微结构等变化，深入探讨针刺俞募穴治疗STC的部分作用机制，为针刺治疗胃肠疾病的临床运用提供研究证据。

慢传输型便秘（STC）是严重影响人们生活质量的临床常见病。近来研究表明胃肠道Cajal细胞（ICC）过度自噬是STC的关键发病机制。本研究以STC模型大鼠为研究对象，对比俞募配穴针刺与非经非穴针刺、假针刺对STC模型大鼠胃肠传输功能及ICC自噬水平的影响。研究结果显示：（1）STC大鼠胃肠传输功能发生障碍，结肠ICC数量与结构异常且存在过度自噬；（2）与假电针组、非经非穴组相比，电针大肠俞募穴可以显著改善STC大鼠胃肠传输功能障碍，促进结肠ICC数量及结构的恢复；（3）电针大肠俞募穴可能通过下调结肠ICC自噬相关蛋白Beclin1、LC3II表达，上调P62表达，以抑制ICC过度自噬，促进ICC的再生和修复，改善肠道传输功能而发挥对STC的治疗作用。本研究从自噬角度阐释俞募配穴治疗STC的效应机制，为今后针刺治疗胃肠疾病的机制研究提供新的思路与借鉴。