迷走神经介导的Th1/Th2细胞分化调节在电针治疗术后肠麻痹中的作用

Postoperative ileus (POI) is a common complications after surgery. It seriously delay the recovery of patients. Ours and other’s clinical studies have shown that electroacupuncture (EA) can significantly shorten the recovery time of postoperative bowel function, but the mechanism is still unknown. A recent study has shown that the imbalance of CD4+ T cell differentiation leading to lower percent of T helper type 2 cell (Th2), and higher percent of T helper type 1 cell (Th1) ,increasing the gamma interferon (IFN -γ) release and then triggering inflammatory reaction, plays a key role in mediating POI. The differentiation of CD4+ T cell into Th1 cell is inhibited by activated cholinergic receptor. Meanwhile EA can improve the excitability of cholinergic nerve, such as the vagal nerve. Based on all above, we hypothesize that vagal nerve modulated Th1/Th2 cells differentiation, resulting in reduction of Th1 cell number and IFN-γ release, is one of the most important mechanisms of how EA promote the recovery of POI. First, we will detect Th1/Th2 cells differentiation in intestinal muscularis, and evaluate the inflammatory reactions and gastrointestinal motor function in a mouse model of POI after EA treatment. Furthermore, we will use interventions like Th1 cell transfusion, T-bet knockout, the vagal nerve blockage，and choline receptors blockage to clarify that vagal nerve plays the key role in regulating Th1 / Th2 differentiation. This project is trying to explain the mechanism of how EA improve the recovery of POI in the perspective of neuro-immuno-modulation, and provide the theoretical basis for optimizing the clinical application of EA on treatment on POI.

术后肠麻痹（POI）是手术后常见并发症，严重影响患者快速康复。本课题组和其他学者的临床研究表明，电针可显著缩短术后肠功能恢复时间，但机制不明。近年研究显示，CD4+T细胞分化失衡，导致辅助性T细胞2（Th2）减少，Th1增多，释放γ干扰素（IFN-γ），启动炎性反应是引起POI的关键机制。鉴于激活胆碱能受体抑制CD4+T细胞向Th1分化，且电针可提高胆碱能神经（如迷走神经）兴奋性，我们推测：迷走神经介导的Th1/Th2分化调节，减少Th1数目和IFN-γ释放是电针治疗POI的重要机制。本项目拟采用小鼠POI模型，观察电针对肠道Th1/Th2分化、肠道肌层炎症反应、胃肠功能的影响，通过输注活化Th1、T-bet转录因子敲除、阻断迷走神经、阻断胆碱能受体等干预手段，明确迷走神经介导的Th1/Th2分化调节的关键作用，旨在从神经免疫角度阐释电针机理，为促进电针在治疗POI中的应用提供理论依据。

背景：术后肠麻痹（POI）是手术后常见并发症，可导致住院发病率升高、住院时间延长、花费增多，目前尚缺少有效治疗手段。临床研究表明，针刺可改善术后肠麻痹，但具体机制不明。近年研究显示，手术操作可导致辅助性T细胞1（Th1）异常增多，Th1细胞特异性释放γ干扰素（IFN-γ），激活肠道巨噬细胞，启动炎性反应，是引起POI的关键机制。.方法及结果：本项目采用肠推挤操作制备POI小鼠模型，观察了电针足三里，对肠道和血中Th1细胞、肠道肌层炎症反应、胃肠推进功能的影响。研究发现电针足三里能促进术后结肠推进功能的恢复，抑制肠道炎性反应；通过输注活化Th1细胞、使用PTX抑制Th1细胞，发现电针治疗术后肠麻痹的作用与Th1细胞有关；进一步，通过阻断迷走神经和胆碱能神经受体等干预手段，发现迷走神经切断使得电针抑制Th1细胞功能的作用削弱，同时电针改善POI小鼠肠道炎性反应的作用也被削弱，此干预削弱了电针改善POI小鼠结肠推进功能的作用。.结论：证明了迷走神经介导的Th1细胞分化的调控在针刺治疗POI过程中起关键作用。本研究从神经免疫调节角度阐释电针作用机理，为促进电针治疗术后肠麻痹的临床应用提供理论依据。