基于scRNA-seq平台探究益气祛痰针法促进肥胖小鼠ENSPC再生机制

肥胖患者或模型动物的肠神经系统处于过度丢失状态，电针减肥具有补偿效应。但是，食源性肥胖与电针减肥如何调节介导再生的肠神经前体细胞（ENSPC）谱系及其生物学特征，是在较大学术争议的前沿科学问题。本项目提出假说：益气祛痰针法促进ENSPC再生, 补偿高脂所致ENS细胞丢失，修复肠道脂代谢功能，达成消脂减肥目标。拟复制高脂肥胖模型小鼠，观测造模及针刺治疗过程之中，小肠及结肠肌肉神经丛神经元与胶质细胞丢失状况；采用单细胞RNA 测序平台研究肥胖造模及针刺治疗等因素对ENSPC细胞图谱、再生功能、细胞密度与空间分布的调控机制 ；将肠肌层神经丛、ENSPC与脂滴、软脂酸或油酸共培养，观察病理特征，测定增殖指数，鉴别ENSPC标记基因与信号通路。本项目聚焦肠神经干细胞学科发展前沿，从高脂肥胖模型与电针减脂之独特研究路径，可望拓展ENS再生研究领域，推进中西医结合肥胖防治研究。

Both neurons and glial cells in the enteric nervous system (ENS) of obese patients or animals are in the state of excessive loss, and electroacupuncture has obvious compensatory effect of ENS regeneration. However, how high-fat induced obesity and electroacupuncture can regulate the regeneration of intestinal neural progenitor cell (ENSPC) lineage and its biological characteristics is a leading scientific issue in a great academic debate. This project puts forward the hypothesis: Yiqi Qutan acupuncture can promote the regeneration of ENSPC, compensate the loss of ENS cells caused by high fat, repair the function of intestinal fat metabolism, and achieve the goal of reducing fat and weight. In the process of model establishment and acupuncture treatment, the loss of neurons and glial cells in muscle plexus of small intestine and colon was observed. The single cell RNA sequencing platform was used to study the regulatory mechanism of obesity model establishment and acupuncture treatment on enspc cell map, regeneration function, cell density and spatial distribution In order to identify the marker genes and signal pathways related to the regeneration of enspc, we co cultured the enteric plexus, enspc with lipid droplets, palmitic acid or oleic acid, observed the pathological characteristics, measured the proliferation index. This project focuses on the development frontier of the subject of enteric neural stem cells. From the unique perspective of high-fat obesity model and electroacupuncture fat reduction, it is expected to expand the research field of ENS regeneration and promote the research of obesity prevention and treatment combined with traditional Chinese and Western medicine.