经皮穴位电刺激抗深静脉血栓形成的血管内皮机制研究

Deep vein thrombosis (DVT) is a common complication during post-operative period, if left untreated, can lead to lethal pulmonary embolism. Recently, our group reported that transcutaneous electrical acupoint stimulation (TEAS), a therapeutic approach based on theories of traditional Chinese medicine, reduced incidence of DVT in post-operative cancer patients, although the underlining mechanism remains unknown. Accumulating evidence has revealed that disturbance caused by venous dilation or local hypoxia activates endothelium, resulting in release of procoagulant proteins such as tissue factor and cytokines to promote leukocyte adhesion and initiate thrombosis. Our preliminary data suggested electroacupuncture attenuated inflammatory response thru activation of both peripheral sympathetic and parasympathetic nerve systems, which then acted in a cooperative manner. Given that endothelial cells express receptors to autonomous nerve neurotransmitters and their activation is repressed by cholinergic agonist, we postulate that TEAS prevents DVT via the de-activation of venous endothelial cells. We thus propose, using an electrolysis-induced rat DVT model, to investigate the effects of TEAS on the morphology and biological functions of endothelial cells, the amount of procoagulant proteins these cells release, and eventual thrombosis formation. We will further use nerve blockade techniques and neurotransmitter receptor antagonists to identify the autonomous nerve system dominated, functionally activated/modulated endothelial cells as the therapeutic target of TEAS. The results from these studies will offer better understanding and better application for this newly developed TEAS technology.

深静脉血栓（DVT）是术后常见并发症，可引起致死性肺栓塞。本课题组应用经皮穴位电刺激（TEAS）预防术后DVT，取得显著效果，并在国际上首次报道了这项基于中医理论的新疗法，但机制不明。最新研究表明，静脉扩张和局部低氧可使血管内皮活化，释放组织因子启动凝血反应，形成血栓，即内皮活化是诱发DVT的关键环节。而本课题组前期研究显示，针刺可激活外周迷走和交感神经，通过两者协同作用，抑制炎性反应。鉴于血管内皮表达自主神经受体，且激活尼古丁受体可抑制内皮活化，我们推测：内皮可能是TEAS经自主神经系统发挥抗DVT作用的靶点。本项目拟采用电解激活内皮诱发DVT的大鼠模型，观察TEAS对内皮形态和功能、促凝蛋白释放、血栓形成的影响，并采用神经阻断、受体功能拮抗等手段，明确自主神经介导的内皮功能调控是TEAS抗DVT的关键，从而阐释其内在的现代科学机理，并为优化这一新疗法提供理论依据。

深静脉血栓是术后常见并发症，可引起致死性肺栓塞，本课题组应用经皮穴位电刺激预防术后DVT，取得显著效果，并在国际上首次报道了这项基于中医理论的新疗法，但机制不明确。最新研究表明，静脉扩张和局部低氧可使血管内皮活化，释放组织因子，启动凝血反应，形成血栓，即内皮活化是诱发DVT的关键环节，而本课题组前期研究显示，针刺可激活外周迷走和交感神经，通过两者协同作用，抑制炎性反应。本项目采用电解激活内皮诱发DVT的大鼠模型，观察TEAS对内皮形态和功能、促凝蛋白释放、血栓形成的影响，检测结果显示DVT+TEAS Zusanli 组较模型组可以下调TNF-α含量、血浆可溶性P选择素含量、TF含量和IL-1β含量，上调vWF含量、NO含量、 TM含量和eNOS含量，差异均具有统计学意义（P＜0.05）。进一步采用神经阻断、受体功能拮抗等干预手段，实验数据显示：DVT+足三里+膈下迷断较DVT+足三里+膈下迷断假手术组，P选择素和TNF-α含量明显升高，NO含量明显降低。DVT+足三里+美加明组较DVT+足三里+生理盐水组，P选择素含量、TNF-a含量明显增加，eNOS表达量、TM表达量明显下降。DVT+足三里+双肾上腺摘除较DVT+足三里+双肾上腺摘除假手术组P选择素和TNF-α含量明显增多，NO含量明显减少。鉴于血管内皮表达自主神经受体，且激活尼古丁受体可抑制内皮活化，我们认为内皮是TEAS经自主神经系统发挥抗DVT作用的靶点，且迷走神经自主介导的内皮功能调控是TEAS抗DVT的关键，从而阐释了其内在的现代科学机理，并为优化这一新疗法提供理论依据。