针灸激活皮肤的脑-皮轴：穴位非特异效应的生物学机制

It was proved in clinic that acupuncture and moxibustion can treat about 400 kinds of disease. This indicated that the effects of acupuncture were induced by regulating the homeostasis of the body. Recent research focused on the specific functions of acupoints but the general functions are ignored. However the general functions of acupoints are the basis of acupuncture therapy. Recent studies show that there is a brain-skin system and it is very similar with hypothalamus-pituitary-endocrine system in the central nerve system. This discovery sheds light on elucidating mechanism of acupoint general functions and brings a new field for research of acupoints. Based on the brain-skin system, the present proposal focuses on the general function of acupoints. We want to prove the mechanism of the general function of acupoints is induced by activating the HPA and HPO in the local acupoints to regulate the local neuroendocrine immune network. The hormones, neurotransmitter and cytokine by acupuncture are produced and released in the local points and diffused into the blood system. At the same time the central neuroendocrine immune network is activated to regulate the target organs. Taken together the general effects of acupuncture are fulfilled by multiple targets of steady state regulation. The changes of HPA and HPO in local acupoints and central nerve system will be analyzed by employing immunohistochemistry method and western blot. Furthermore the changes hormones, neurotransmitter and cytokine in the blood will be measured by ELISA after acupuncture therapy. All in all the general functions of acupoints are caused by the changes of local and central HPA and HPO to influence the target organs.

针灸对四百多种疾病有积极的调节作用表明针灸主要是通过调节机体稳态系统发挥作用。与穴位特异性效应相比，针灸穴位产生非特异性（普适性）的稳态调节效应还没得到重视。而新近发现的皮肤中脑-皮轴系统（皮肤具有与中枢相似的下丘脑-垂体-内分泌系统）对直接作用于皮肤的针灸疗法带来了创新性研究领域。本研究从脑-皮轴切入，以穴位始动—脑-皮轴系统响应—靶器官效应为主线，拟阐明针灸通过调节穴位局部HPA和HPO轴释放激素、神经递质和细胞因子，同时激活中枢神经内分泌免疫网络，调节靶器官，完成针灸效应的多靶点、多环节的稳态调节。采用酶联免疫、免疫组化、Western blot、荧光定量PCR及基因敲除等技术观察针灸引起的穴位皮肤及中枢HPA、HPO轴的改变，分析针灸穴位效应的始动机制，比较针灸后血液中激素、神经递质、细胞因子的改变，从穴位—脑-皮轴系统—靶器官效应三个层次揭示穴位针灸引起的普适性调节效应及其机制。

以往我们重视穴位特异性研究，证明穴位通过节段性和全身性的神经调节完成对靶器官的特异性调节。但是国外大量的浅刺对照有效的临床报告，对穴位特异性提出质疑，提示我们穴位还有非特异性的局部和全身的调节作用。本研究聚焦于此。近十年形成的脑皮轴的理论，为穴位功能的广泛性研究奠定了基础。脑皮轴是指皮肤具有与中枢相似的下丘脑-垂体-肾上腺系统，即皮肤的HPA轴。本研究的结果表明：1. 针灸刺激激活穴位局部和全身的脑-皮轴发挥广谱的调节效应：电针足三里（ST36）可引起穴位局部HPA相关激素显著升高；热灸刺激ST36主要引起血液中HPA相关激素的显著升高。电针合谷（LI4）可引起穴位局部HPA相关激素的增加，热灸LI4引起血浆中HPA轴相关激素的表达增加。2. 针灸刺激引起穴位局部神经肽-肥大细胞的组织细胞化学变化：电针、热灸以及经皮穴位电刺激（TEAS）不同穴位均可引起穴位局部神经肽SP和CGRP的表达增加，肥大细胞聚集脱颗粒，释放5-HT和组织胺（HA）。TRPV1敲除后这一反应明显下降。3. 针灸刺激对穴位局部和全身细胞因子的影响：电针和热灸刺激ST36可分别引起穴位局部和血清中细胞因子的改变，针刺后局部细胞因子增高，可能是由于局部微小的刺激仅引起局限性的的炎症和抗炎免疫有关，而热灸激活的感受器范围相对较大，引起大面积的神经-血管反应，血液中的细胞因子增加比针刺明显。这种变化可以解释临床上针和灸的不同治疗作用。也是穴位广泛性作用的一种体现。4.针灸穴位对HPO轴的调节：针刺治疗可以显著改善更年期综合征患者的Kupperman症状评分，增加E2含量。针刺可以显著改善PCOS的临床症状，针刺治疗后血清FSH，LH明显改善，LH/FSH值均极显著下降。本课题的结果表明：电针或热灸刺激对于穴位局部及全身HPA轴HPO轴，释放神经肽，内分泌激素和细胞因子，发挥穴位局部和全身的广泛性调节作用。