基于肠胶质细胞活化和NGF/TrkA通路介导的突触重塑探讨疏肝健脾方对腹泻型肠易激综合征的作用机制
批准号:
82004266
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
卢小芳
依托单位:
学科分类:
中医内科学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
卢小芳
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中文摘要
腹泻型肠易激综合征(D-IBS)是临床常见病,肠道高敏感是其重要病理机制,疏肝健脾法是其中医基本治法。依法立方,团队前期研究发现疏肝健脾方可缓解D-IBS大鼠肠道高敏感状态,且可降低结肠NGF、TrkA含量,提示NGF/TrkA信号通路在疏肝健脾方调节D-IBS肠道感觉中发挥一定作用。但目前疏肝健脾方作用此信号通路的上下游靶点尚不明确,还有待探讨。近些年随着“肠脑”概念的提出,肠神经突触重塑在肠道感觉异常相关疾病中的作用凸显,且受到肠胶质细胞(EGC)分泌的NGF等生长因子的调控。基于此,本项目提出假说:“疏肝健脾方治疗D-IBS可能是通过调节EGC活化和NGF/TrkA通路相关的突触重塑实现的”,主要应用电子恒压器、免疫荧光双染、透射电镜、细胞培养等技术探讨疏肝健脾方对D-IBS大鼠肠道敏感性、EGC活化、NGF/TrkA通路、突触重塑的影响。这对丰富完善疏肝健脾方治疗机制具有一定意义。
英文摘要
Diarrhea-predominant irritable bowel syndrome (D-IBS) is a common clinical disorder, in which intestinal hypersensitivity is an important pathological mechanism and Shugan-Jianpi method is the basic method of traditional Chinese medicine. In our previous study, it was found that Shugan-Jianpi decoction could alleviate the intestinal hypersensitivity and reduce the colonic level of NGF and TrkA in D-IBS, suggesting that NGF/TrkA signaling pathway played a role in the effect of Shugan-Jianpi decoction on the intestinal sensation in D-IBS. However, at present, the upstream and downstream targets of Shugan-Jianpi decoction related with the signaling pathway have not been clear yet, which need to be discussed. In recent years, based on the concept of "gut brain" put forward, the synaptic plasticity in the enteric nervous system has received more and more attentions in the diseases associated with intestinal paresthesia, which is regulated by the growth factors such as NGF secreted by enteric glial cells (EGC). Based on the above, a hypothesis will be proposed:" the treatment of Shugan-Jianpi decoction for D-IBS may be achieved through regulating the synaptic plasticity, which mediates by the activation of EGC and the change of NGF/TrkA pathway". We will mainly discuss the effect of Shugan-Jianpi decoction on the intestinal sensitivity, EGC activation, NGF/TrkA pathway and synaptic plasticity by means of electric barostat, immunofluorescence double staining, transmission electron microscopy, cell culture and other techniques, which will have certain significances to enrich and perfect the therapeutic mechanisms of Shugan-Jianpi decoction.
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DOI:10.2147/dddt.s423333
发表时间:2023
期刊:DRUG DESIGN DEVELOPMENT AND THERAPY
影响因子:4.8
作者:Lu, Xiaofang;Zhang, Shengsheng
通讯作者:Zhang, Shengsheng
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