电针足三里兴奋迷走神经抗失血性休克的多巴胺机制研究

Sympatho-adrenomedullary system excessive excitement duce to sharply decrease of circulating blood volume，releasing a large number of hypertensive substances like catecholamine causes continuous peripheral vascular contraction and microcirculatory ischemia, which is a key factor of the development and progression of hemorrhagic shock(HS). At this time, suppression of the sympathetic nerve excitability, and reduction of the release of the vasoconstrictor substances may prevent the progress of HS. Literatures and previous studies have shown that dopamine (DA) and norepinephrine (NE) ratio was reduced during early stage of HS, electricacupuncture(EA) at ST36 or electrical stimulation of the vagus nerve increased plasma levels of dopamine against HS, while vagotomy or adrenalectomy or receptors blocking abolished the effect of EA. We assume that the EA ST36 increases dopamine against HS by activating vagal and adrenal medulla function, and regulating the production of dopamine, which may act on the DA1 receptor, promoting abdominal visceral vasodilation, increasing blood flow and urine amount, and alleviating capillary contraction and microcirculatory disturbance. The content of this research is: First using the animal model of severe HS or HS with delayed fluid resuscitation confirms the effect of EA ST36 or the stimulation of vagus nerve against shock. Furthermore, performing vagotomy or adrenal demedullation or blocking dopamine DA1 receptors respectively, to explore the mechanism of the EA ST36 against HS through activating vagus, affecting adrenal medulla function and dopamine metabolism enzyme, and regulating the ratio of dopamine to norepinephrine via DA1 receptor.

循环血量骤减引起交感-肾上腺髓质系统过度兴奋，释放大量儿茶酚胺类升压物质，短时内可维持心脑血供，但持续收缩外周血管、导致微循环障碍使失血性休克（HS）发展、恶化。此时，对抗交感兴奋性、减少缩血管物质释放，能阻止休克进展。文献和前期研究表明HS早期多巴胺（DA，能扩张心、脑及腹腔脏器血管，增加血流量和尿量）与去甲肾上腺素（NE）比值降低，电针足三里能抗HS并升高DA，而切断迷走神经（VN）、切除肾上腺或阻断DA1受体会降低抗休克作用。因此假设电针足三里能兴奋VN、调节肾上腺髓质功能及DA生成，增加DA释放，升高DA/NE比值，作用于DA1受体，缓解微循环障碍和HS。拟采用重度HS和HS延迟输液动物模型，确认电针抗HS及输液替代作用。然后分别切断VN、肾上腺去髓质化或阻断DA1受体，探讨电针足三里是否兴奋VN、影响肾上腺髓质功能及DA合成酶，调节休克时DA/NE比值，通过DA1受体抗HS的机制

项目研究背景：循环血量骤减引起交感-肾上腺髓质系统过度兴奋，释放大量去甲肾上腺素（NE）类升压物质，持续收缩外周血管、是导致失血性休克（HS）恶化的关键因素。对抗交感兴奋性、减少缩血管物质释放，能阻止休克进展。本研究假设电针足三里（简称EA）能兴奋迷走神经（VN）、影响肾上腺髓质功能及多巴胺酶活性，增加多巴胺（DA，能扩张心、脑及腹腔脏器血管，增加血流量和尿量）释放，升高DA与NE等缩血管物质的比值，缓解微循环障碍和HS。主要研究内容：①采用重度HS延迟输液动物模型，确认电针抗HS和输液替代作用；②分别切断VN、去除肾上腺髓质、抑制或激活DA受体，探讨EA能否兴奋VN、影响肾上腺髓质功能及DA合成酶、调节休克时DA/NE比值，并通过何种DA受体发挥抗HS的机制。重要结果及关键数据：①EA能有效提高致死性HS大鼠平均动脉压，增加腹腔脏器血流量，减轻脏器功能损害，延长平均生存时间，提高早期生存率。提示在HS救治现场无即刻输液条件时，EA能部分替代常规静脉输液的作用。②去除肾上腺髓质能显著降低HS大鼠平均动脉压、脏器血流量及生存率，并且完全消除EA的抗休克作用，从而确认EA主要通过影响肾上腺髓质功能发挥抗HS作用。③EA能提高肾上腺髓质多巴胺脱羧酶含量及活性、增加DA产生，升高血中DA水平；同时降低肾上腺髓质多巴胺羟化酶含量及活性，减少EN生成，从而增高DA与NE比值，发挥抗休克作用。④多巴胺DA1受体激动剂能增强电针的抗HS作用，增加内脏血流量和尿量，保护肠屏障和腹腔脏器功能。抑制DA1能消除电针的抗休克效应，而激动或抑制DA2无影响，证明EA能通过迷走神经-肾上腺髓质系统，释放低水平的DA，作用于心、脑和腹腔脏器血管DA1受体，发挥抗休克作用。科学意义和应用前景：研究为针灸抗各种休克和多器官损害提供了新的理论依据和技术手段。针刺抗休克疗效确切、简易可行，能部分替代静脉输液、适合战场、突发事故或灾害现场休克伤员的急救，具有军事医学、急救医学和灾害医学应用价值。