microRNAs调控ICCs在电针治疗功能性消化不良中的新机制

Interstitial cells of Cajal (ICCs) ,as pacemaker cells for generation of slow waves in the GI tract , are of vital clinical significance in the research of GI motility disorders. Our previous studies found a mechanism in the treatment of functional dyspepsia(FD) that electric acupuncture(EA) could validly maintain the structure, besides, modulate proliferation and differentiation of ICCs, and then restore the GI dysfunction of FD based on the changes of SCF/c-kit pathway. Due to the initiation of SCF/c-kit pathway and the subsequent cascade reaction induced by miRNAs, GI motility has potentially been influenced. We speculate that there is a novel mechanism by which miRNAs regulate the ICCs involved in EA treatment of FD. On the basis of preliminary work, further study focuses on the research of specific reaction of miRNAs regulating target gene c-kit and ICCs during the intervention of EA on FD. In this study, we attempt to reveal the basal relationship between the expression of miRNAs and the effect of EA promoting GI motility , thus providing a new theoretical and experimental evidences for acupuncture therapy on FD.

Cajal间质细胞（interstitial cells of Cajal, ICCs）作为胃肠道慢波活动的起搏细胞，在胃肠动力障碍的研究中有着重要的临床意义。我们以往的研究发现，电针在干预功能性消化不良（functional dyspepsia, FD）过程中存在着以SCF/c-kit通路变化为基础，调节ICCs细胞的结构、增殖和分化，进而恢复FD胃肠功能障碍的机制。多种miRNAs参与调节SCF/c-kit通路及其级联反应，影响着胃肠道运动功能。我们推测存在一种miRNAs调控ICCs参与电针治疗FD的新机制。本项目在前期工作基础上，深入研究电针治疗FD过程中，miRNAs对靶基因c-kit和ICCs调节的具体效应环节。藉此研究，我们试图基于电针干预FD的治疗学基础，发现一种miRNAs表达变化与电针发挥促胃肠动力作用之间的内在联系，为针刺治疗FD提供新的理论和实验依据。

胃肠动力障碍是功能性消化不良（FD）发生的重要病理生理基础，而Cajal间质细胞（interstitial cells of Cajal, ICCs）是胃肠道慢波活动的起搏细胞，可产生慢波和传导电兴奋，c-kit是ICCs的特异性标志物基因，SCF为c-kit的特异性配体，能与c-kit通过胞外结构域结合。本项目以多因素刺激法构建的FD模型大鼠为实验对象，采用电针干预，观察电针对FD的治疗作用，检测其过程中的差异性microRNAs。选取miR-221-3p为例，经大鼠尾静脉分别注射miR-221干扰载体和过表达载体，检测miR-221-3p介导电针调控ICCs治疗FD大鼠的作用机制。结果发现，在电针治疗过程中，miR-221-3p能够通过下调SCF/c-kit和Raf/Erk信号通路来影响ICCs，从而影响电针对FD的治疗作用。研究结果为FD的防治提供了新的思路和实验依据，具有较高的临床应用价值，产业化前景较好。