针刺治疗功能性便秘的肠道菌群和肠道动力交互作用机制研究

功能性便秘（FC）是临床常见病，现代医学缺乏有效干预手段。课题组前期研究已证实针刺治疗该病疗效确切、安全性高。前一个面上项目发现针刺可促使EGC分泌GDNF、调控ENS-ICC-SMC功能网络以促进肠道动力。最新研究表明肠道菌群紊乱与FC的发生发展密切相关，而EGC作为肠道菌群作用的靶细胞，是菌群和动力交互作用的枢纽。针刺对肠道菌群和动力均有良好调节作用。据此，项目组提出如下假说：针刺可能通过调控EGC介导的TLR2-NF-κB-GDNF信号通路影响肠道菌群和肠道动力的交互作用，恢复二者动态平衡，改善肠道功能。因此，本项目以FC小鼠模型为研究载体，以针刺大肠合募穴为干预措施，采用高通量测序、免疫荧光结合激光共聚焦显微镜等技术，并引进无菌小鼠和TLR2-/-小鼠，从正、反两面揭示EGC、肠道菌群、肠道动力和TLR2信号通路在针刺改善肠道功能中的作用机制，为针灸优势病种的推广应用提供科学依据。

Functional constipation is a common clinical disease. Modern medicine has no effective interventions. Our research group has confirmed that acupuncture is effective and safe for the treatment of FC, and the previous project supported by National Natural Science Foundation of China found that acupuncture can promote the GDNF expression in EGC, regulate the ENS-ICC-SMC function network to promote intestinal motility. Recent studies show that intestinal flora disorder is closely related to the occurrence and development of FC, moreover, as the target cell of intestinal flora, EGC is the key to the interaction of flora and dynamics. A number of studies have shown that acupuncture has a good effect on intestinal flora and motility. According to the above description , our project team put forward the following hypothesis: Acupuncture may affect the interaction between intestinal flora and intestinal motility by regulating the TLR2-NF-κB-GDNF signaling pathway mediated by EGC, to restore the homeostasis and improve the intestinal function. In this study, functional constipation mice are used as the research object, and acupuncture is used as an intervention to improve the intestinal function. Using high-throughput sequencing, immunofluorescence labeling combined with laser confocal microscopy and other technologies, also utilizing germ-free mice and TLR2 knockout mice, to reveal the mechanism of EGC, intestinal flora, intestinal motility and TLR2 signaling pathway in improving intestinal function by acupuncture, and to provide the scientific basis for the popularization and application of acupuncture in treating dominant diseases.