针刺抑制EGC网络的瀑布级联效应缓解IBS内脏高敏的机制研究

Irritable bowel syndrome (IBS) is one of most common functional bowel diseases. Visceral hypersensitivity is the most important pathological mechanism and manifestation of IBS. Nowadays, with the obvious side effects, find a safe and effective method is needed. It is reported that puncturing Tianshu with Taichong is able to relieve the symptom of abdominal pain and distention. However, the mechanism of acupuncture for IBS patients with visceral hypersensitivity is still unclear. Recent studies indicated that the dysfunction of EGC network resulting from cascade effect activated among triggered EGC is the key point in pathogenesis of visceral hypersensitivity. Studying on this network is probably a way to explore the visceral mechanism of peripheral. Therefore, we hypothesis that acupuncture can relieve the visceral hypersensitivity of IBS patients by regulate the EGC and cascade effect of its network. We plan to use IBS model rats with visceral hypersensitivity as the research subjects, focus on the point that acupuncture can reduce the level of BDNF, suppress the overactivity of EGC and its gup junctions which contribute to cascade effect, improve the function of EGC network, and relieve the visceral hyperactivity, utilize techniques such as immunohistochemistry, in situ hybridization with computer graphics analysis, RT-PCR to research on the regulation effects of acupuncture on visceral sensitivity.

肠易激综合征（IBS）是发病率最高的一类功能性肠病。内脏高敏是IBS重要的病理机制之一。目前药物治疗症状反复，副作用明显，如何寻求安全有效的治疗方法是亟待解决的问题。针刺缓解IBS患者腹痛、腹胀等内脏高敏症状疗效肯定，但其作用机制有待深入研究。最新研究表明，肠道胶质细胞（EGC）活化诱发瀑布级联效应所致的EGC网络功能异常是促进和维持IBS内脏高敏发生发展的关键环节。本课题以IBS内脏高敏模型大鼠为研究对象，以促进和维持内脏高敏的EGC及其网络瀑布级联效应为切入点，从BDNF/TrkB-PLC-Ca2+信号通路入手，通过免疫组化、原位杂交结合计算机图像分析、RT-PCR等技术手段，围绕“针刺通过下调BDNF含量，抑制EGC活化和缝隙连接所形成的瀑布级联效应，改善EGC网络功能状态，缓解IBS内脏高敏状态”这一假说，深入探讨针刺治疗IBS内脏高敏的作用机制。

肠易激综合征（IBS）是发病率最高的一类功能性肠病，以腹痛、大便异常为主要症状，其症状迁延难愈，严重损害了患者的身心健康。目前药物治疗，症状反复，副作用明显，患者治疗满意度低，如何寻求安全有效的治疗方法是亟待解决的难点问题。内脏高敏是IBS典型且重要的病理机制之一，针刺缓解IBS患者腹痛、腹胀等内脏高敏症状疗效确切，优势突出，但其作用机制尚待深入研究。科学阐释针刺治疗IBS内脏高敏的作用机制，有助于促进针刺治疗IBS的临床应用和推广。.最新研究表明，肠道胶质细胞（EGC）活化诱发瀑布级联效应所致的EGC网络功能异常是促进和维持IBS内脏高敏发生发展的关键环节。本课题以IBS内脏高敏模型大鼠为研究对象，以促进和维持内脏高敏的EGC及其网络瀑布级联效应为切入点，从BDNF/TrkB-PLC-Ca2+信号通路入手，通过免疫组化、原位杂交结合计算机图像分析、RT-PCR等技术手段，围绕“针刺通过下调BDNF含量，抑制EGC活化和缝隙连接所形成的瀑布级联效应，改善EGC网络功能状态，缓解IBS内脏高敏状态”这一假说，深入探讨针刺治疗IBS内脏高敏的作用机制。.研究结果表明：①针刺可提高IBS-D大鼠腹壁撤退反射（AWR）阈值，缓解IBS状态下的内脏高敏；②针刺通过减少结肠黏膜下及肌间神经丛内EGC数量、标志性蛋白GFAP和S100B表达水平，从而降低EGC活性；③针刺通过减少肠道缝隙连接蛋白Cx43的表达，减少EGC网络的形成；④针刺通过抑制EGC活化和网络形成，减少肠道黏膜下组织中P物质表达水平；⑤针刺可能是通过抑制BDNF/TrkB-PLC信号转导通路，减少EGC内Ca2+水平，从而抑制EGC的活化；而采用TrkB受体激动剂后，可抵消针刺抑制EGC活化及网络形成、缓解内脏高敏的作用。.本课题采用TrkB受体激动剂，从正反面双向验证针刺对BDNF/TrkB信号通路的调节作用，初步证实了针刺可以通过下调BDNF/TrkB信号通路中关键分子，抑制EGC细胞过度活化，缓解IBS内脏高敏状态，为针刺治疗IBS内脏高敏的作用机制提供科学证据，有利于针灸在该类疾病中的临床推广。