正天丸干预血管活性物质所致偏头痛的机制研究

TCM believes that " obstruction of collaterals by blood stasis, stagnation of QI and blood may bring about pain" are closely related, study confirmed that patients with migraine with blood high viscosity, high coagulation state and poor circulation change, in line with the characteristics of thick, sticky, coagulation of blood stasis. Modern research indicates migraines, seizures and endogenous vasoactive substances and neurotransmitters in the cerebral vasomotor dysfunction is closely related to 5-hydroxy tryptamine ( 5-HT ) and its receptor, nitric oxide ( NO ), Colcition gene-rolated pepthde ( CGRP ) is particularly close. By promoting blood circulation and removing blood stasis Zhengtian pill effect in the clinical treatment of migraine was significantly, so this research to clear syndrome " migraine " as the carrier. Use migraine rat model induced by subcutaneous injection of nitroglycerin and experimental migraine model by low 5-HT with cerebral vasospasm to investigate the Zhengtian pill respectively on two models of therapeutic effect of migraine rats. With 5-HT-NO-CGRP as the main line, content by real-time fluorescence quantitative PCR, high performance liquid chromatography, radioimmunoassay method for the detection of 5-HT, NO, CGRP, study of migraine attack the three main types of relationships between the depth of vasoactive substances, Zhengtianwan pill in treating migraine mechanism.

中医认为偏头痛与"瘀血阻络，不通则痛"密切相关，研究证实偏头痛患者血液呈高粘、高凝状态和流动性差等改变，符合了中医瘀血浓、黏、凝、聚的特点。现代研究认为偏头痛的发生、发作与内源性血管活性物质及神经递质引起脑血管舒缩功能障碍密切相关，其中以5-羟色胺（5-HT）及其受体、一氧化氮（NO）、降钙素基因相关肽（CGRP）尤为密切。以活血化瘀为主的正天丸在偏头痛的临床治疗中效果显著，故本课题以辨证明确的"偏头痛"为载体，选用皮下注射硝酸甘油所致的大鼠偏头痛模型和利血平化低5-HT伴局部脑血管痉挛的实验性偏头痛模型来考察正天丸分别对二种偏头痛大鼠模型治疗作用，以5-HT-NO-CGRP为主线，通过荧光实时定量PCR、高效液相色谱、放射免疫等方法检测5-HT、NO、CGRP的含量，研究偏头痛发作时这三种主要血管活性物质之间的相互关系，深入探讨正天丸治疗偏头痛的内在作用机制。

偏头痛患者血液呈高粘、高凝状态和流动性差等改变，符合了中医瘀血浓、黏、凝、聚的特点。偏头痛的病理机制与内源性血管活性物质及神经递质引起脑血管的舒缩功能障碍密切相关。本项目建立了实验性偏头痛动物模型，观察了中药复方正天丸对偏头痛大鼠模型的疗效，检测了药物对血管活性物质和神经递质含量的影响，并探讨其作用机制。研究结果显示，正天丸可明显延长偏头痛大鼠模型的耳红出现时间，明显减少前肢挠头次数和爬笼次数。与偏头痛模型组比较，正天丸治疗组大鼠脑组织中的γ-氨基丁酸（γ- GABA）、5-羟色胺（5-HT）、去甲肾上腺素（NE）含量明显升高，谷氨酸（Glu)含量明显降低。同时，正天丸可提高热刺激小鼠的痛阈值，延长冰乙酸所致的疼痛小鼠扭体反应潜伏期，减少扭体次数，并能明显缩短甲醛致痛小鼠的Ⅰ、Ⅱ相舔、咬足时间；明显降低甲醛致疼痛模型小鼠血清前列腺素2（PGE2）、脑组织Glu和降钙素基因相关肽（CGRP）含量，显著提高疼痛小鼠外周血中一氧化氮（NO）含量。综上所述，本项目研究表明正天丸可通过调节偏头痛大鼠模型中的血管活性物质NE和神经递质的5-HT、γ- GABA、Glu含量改善偏头痛大鼠的行为学，且具有明显的镇痛作用，其镇痛机制与抑制中枢Glu、CGRP释放，降低外周疼痛介质PGE2含量，促进外周NO合成相关。本项目研究结果可为中药正天丸的临床应用及偏头痛治疗提供数据支持和科学依据。