基于ENS－ICC－SMC网络信号转导通路研究疏肝健脾法对FD肝郁脾虚证胃肠动力障碍的作用机制

Functional dyspepsia (FD) is a disease of Gastrointestinal Motility Dysfunction(GMD) and associated with mental mental disorders. It has many characteristics such as a variety of symptoms overlap, changeable or conversion and repeated episodes difficult to cure, and so on. GMD is the pathological basis of FD, while Traditional Chinese Medicine believe that Liver-depression and Spleen-deficiency is the crux of the problem of FD, the use of the advantage of regulating the whole of Chinese medicine on the treatment have a unique effect. We put forward a hypothesis based on preliminary studies: The GMD of FD with Liver-depression and Spleen-deficiency Syndrome may be closely related to The Network of ENS－ICC－SMC signal transduction pathways. Using the Liver-Soothing Spleen-Strengthening Method (Shuwei Decoction), to established FD of Liver- depression and Spleen-deficiency Syndrome large rat model as study objects by composite causes and Gastrointestinal prokinetic agents Mosapride as a control-medicine, applied multiple technology means such as immune fluorescence method total focused microscope , Western-blot, transmission electric mirror, RT-PCR and so on. From excitatory and inhibitory neuronal-ICC network morphology structure, the network of ICC-smooth muscle signal transduction pathway structure and ICC cell Ca2 signal-regulated mechanism Multiple links to study effect of The Liver-Soothing Spleen-Strengthening Method on FD Gastrointestinal Motility of Liver-depression and Spleen-deficiency Syndrome.

功能性消化不良（FD）是以胃肠动力障碍为主并多伴有心理精神障碍的一种疾病，有多种症状重叠、多变或相互转换以及反复发作、较难治愈等特点。胃肠动力障碍是FD的主要的病理生理学基础，而中医认为肝郁脾虚是FD胃肠动力障碍的症结所在，运用中医药整体调节的优势对其治疗有独特的疗效。我们基于前期研究提出假说：FD肝郁脾虚证胃肠动力障碍可能与胃肠神经－Cajal间质细胞－平滑肌网络信号转导通路密切相关；采用疏肝健脾法（舒胃汤），以复合病因建立FD肝郁脾虚证动物及细胞模型为受试对象，以促胃肠动力药莫沙必利为对照，运用免疫荧光法、Western-blot、透射电镜、RT-PCR等多种技术手段，从ENS－ICC－SMC网络信号通路形态学角度研究疏肝健脾法对FD胃肠动力、胃电节律和神经递质的影响，从细胞信号转导途径探讨疏肝健脾法含药血清对FD的ICC钙离子信号调节机制的分子机理。

功能性消化不良（FD）是以胃肠动力障碍为主并多伴有心理精神障碍的一种疾病，有多种症状重叠、多变或相互转换以及反复发作、较难治愈等特点。胃肠动力障碍是FD的主要的病理生理学基础，而中医认为肝郁脾虚是FD胃肠动力障碍的症结所在，运用中医药整体调节的优势对其治疗有独特的疗效。我们基于前期研究提出假说：FD肝郁脾虚证胃肠动力障碍可能与胃肠神经－Cajal间质细胞－平滑肌网络信号转导通路密切相关；采用疏肝健脾法（舒胃汤），以复合病因建立FD肝郁脾虚证动物及细胞模型为受试对象，以促胃肠动力药莫沙必利为对照，运用免疫荧光法、Western-blot、透射电镜、RT-PCR等多种技术手段，从ENS－ICC－SMC网络信号通路形态学角度研究疏肝健脾法对FD胃肠动力、胃电节律和神经递质的影响，从细胞信号转导途径探讨疏肝健脾法含药血清对FD的ICC钙离子信号调节机制的分子机理。通过本研究实验发现：（1）舒胃汤可能通过改善ICC细胞形态，恢复ICC细胞正常生理功能，促进神经纤维的正常形态和功能的恢复，升高缝隙连接蛋白Cx43的表达，增强ICC与平滑肌之间的缝隙连接，修复完整ENS-ICC-SMC网络样超微结构。（2） 舒胃汤能对FD肝郁脾虚证大鼠胃窦和十二指肠上段组织中Beclin-1、Bcl-2、Caspase12、mTOR、Cx43蛋白和基因表达有提升和降低的作用，推测能通过调控胃肠道平滑肌中自噬与凋亡相关因子含量，治疗FD的治疗功能性消化不良。（3）舒胃汤对胃肠道ICC细胞内IP3R、RyR因子蛋白和mRNA表达有明显的升高作用，提升了ICC细胞内Ca2+浓度，加强细胞信号的传导，从而促进胃肠平滑肌的运动。课题组发表国内核心期刊13篇，其中SCI1篇，培养研究生2名，授权专利1项，撰写书籍1本。