腹泻型肠易激综合征（IBS-D）是常见消化病，肠神经系统（ENS）在IBS-D发病机制中居于中心地位，最新研究发现肌层巨噬细胞（MM）和肠神经元之间的相互对话对于调节胃肠动力、维持胃肠神经稳态至关重要。课题组研究发现：广藿香醇给药后改善大鼠胃肠动力和高敏感性，与改变结肠肌间神经丛神经元及其亚型数目与功能，恢复肠神经稳态和可塑性有关。基于此，本项目聚焦于MM与ENS的cross-talk（互话）调节机制，提出科学假说：广藿香醇通过调控肠肌间神经丛这两种细胞的互话, 影响肠神经元BMP2/Smad1/5/8信号通路以及CSF-1的生成，恢复肠神经稳态、抑制平滑肌高反应性，起到治疗IBS-D的作用。基于这一科学假说，本项目拟采用单细胞RNA测序和全层铺片原位显影等先进技术，探索IBS-D的病理生理新机制，研究广藿香醇对IBS-D模型MM-ENS对话的调控机制。

Enteric nervous system(ENS) Play a core role in mechanisms of irritable bowel syndrome with diarrhea(IBS-D), a common digestive disorders. It has been found that the cross-talk between Muscularis Macrophages (MM) and intrinsic enteric neurons is crucial for gastrointestinal motility and ENS homeostasis. Moreover, our group found that the improvement of gastrointestinal motility and visceral hypersensitivity in IBS-D rats after the administration of Patchouli alcohol was related to morphological and functional changes of neurons and subtypes in the colonic myenteric plexus, as well as the recovery of ENS homeostasis and plasticity. The program is focused on the cross-talk between Muscularis Macrophages(MM) and intrinsic enteric neurons to explore whether Patchouli Alcohol intervenes the cross-talk of these two types of cells in myenteric plexus and interrupt the BMP2/Smad1/5/8 signal pathway and the production of CSF-1 in neurons, by which Patchouli Alcohol recover ENS homeostasis, inhibit hypersensitivity of smooth muscles, and then relieve the symptoms of IBS-D. By using single-cell RNA-seq and whole-mount in situ imaging tech, relative proteins in BMP2/Smad1/5/8 signal pathway and dynamic transcriptomics profile will be investigated to study the mechanism of Patchouli Alcohol on the cross-talk between Muscularis Macrophages(MM) and intrinsic enteric neurons and elucidate the complex mechanism and multi-target action mood of Patchouli Alcohol on enteric homeostasis and motility.