针刺调节术后ICCs修复再生微环境的作用及其microRNA调控

Interstitial cells of Cajal(ICCs) are universally acknowledged as the gastrointestinal pacemaker cell. Damage of ICCs is one of the pathological mechanisms in postoperative gastrointestinal motility disorder. And its restoration and regeneration is closely related to microenvironment. Microenvironment is directly under the control of nerve-endocrine-immune network, which can be affected by acupuncture. Our previous studies showed that acupuncture could effectively promote the repairment of ICCs and ENS-ICCs network and improve postoperative gastrointestinal motility. But its mechanisms remain unclear. MicroRNA(miRNA) is a type of RNA that is found in recent years and it can regulate gene function at the post-transcription level. Through the target genes it is involved in various biological network regulation. In this research we focus on postoperative changes of microenvironment to further explore the effect and mechanism of acupuncture on promoting restoration and regeneration of ICCs: ①Rat model of colonic anastomosis is made. To observe what work has been done in the microenvironment by acupuncture through its endocrine and immune regulative function, level of gaseous signaling molecules such as H2S, CO, NO and the activity of their synzymes are detected. The expressions of immune inflammatory factors like TNF-a, IL-1β, etc., are measured. The changes of Kit/SCF signal pathway are also observed. The cytothesis progress of ICCs is studied at different postoperative time points and its relevance to the microenvironmental changes is analyzed. ②Detect the miRNA changes in microenvironment using miRNA microarray technology, RT-PCR technique and so on. The function ways of acupuncture and its action rules is discussed on the microenvironmental gene regulation level. The result of this research will provide scientific theoretical basis and experimental support for clinical application of acupuncture on regulating postoperative gastrointestinal motility.

Cajal细胞(ICCs)是目前公认的胃肠起搏细胞，其损伤是术后胃肠动力障碍的病理机制之一，其修复再生与微环境密切相关。微环境直接受神经-内分泌-免疫网络影响，而针刺对该网络有良好的调节作用。课题组前期研究表明，针刺能有效促进ICCs和肠神经-ICCs网络修复，改善术后胃肠动力，但其作用机制尚未明确。microRNA(miRNA)是近年发现的一类在转录后水平调控基因表达的RNA，通过靶基因参与各种生物网络调控。本研究拟从微环境的变化着手深入探讨针刺促进术后ICCs修复再生的机制：①横向探索针刺对结肠吻合术后大鼠组织微环境内气体信号分子体系、Kit/SCF信号途径和免疫炎症因子的调节作用，纵向观察该作用与术后不同时点ICCs修复再生进程的相关性；②采用miRNA芯片等技术从微环境的基因调控层面研究针刺的作用途径和作用规律。研究结果将为临床运用针刺改善术后胃肠动力提供科学的理论依据和实验支持。

Cajal细胞(ICCs)是目前公认的胃肠起搏细胞，其损伤是术后胃肠动力障碍的病理机制之一，其修复再生与所在的微环境密切相关。微环境直接受神经-内分泌-免疫网络影响，而针刺对该网络有良好的调节作用。课题组前期研究表明，针刺能有效促进ICCs和肠神经-ICCs网络修复，改善术后胃肠动力，但其作用机制尚未明确。microRNA(miRNA)是近年发现的一类在转录后水平调控基因表达的RNA，通过靶基因参与各种生物网络调控。为深入探讨针刺促进术后ICCs修复再生的机制，本研究从微环境的变化着手，将miRNA引入针刺的机制研究，以结肠吻合术建立ICCs损伤模型，横向观察针刺对ICCs修复组织微环境内的气体信号分子体系、Kit/SCF信号途径和免疫炎症因子的调节作用，纵向观察该作用与术后不同时点ICCs修复再生进程的相关性，并通过microRNA从微环境的基因调控层面研究针刺的作用途径和作用规律。研究结果表明：①针刺能抑制术后应激增加的气体合成酶活性和表达量，从而降低急剧升高的气体信号分子浓度，为ICCs的修复创造有利环境；②在不同的术后鼠类动物模型中针刺均显示出其对ICCs修复的促进作用，且该作用与巨噬细胞，炎症因子，气体及其合成酶的变化具有一定相关性；③在针刺促进ICCs修复和调节微环境气体分子体系的过程中，miRNA发生了变化，提示miRNA可能是针刺发挥效应的中介物质。该研究结果为临床运用针刺调整术后胃肠动力提供了科学的理论依据和实验支持，有利于针刺在治疗术后胃肠动力障碍中的推广应用。