偏头痛病因病机、治法与方药的相关研究
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摘要
偏头痛(migraine)是人类最常见的疾病之一，以其发病率高，易反复发作，迁延难愈，是一个严重影响人类生存质量的重要健康问题。当今的中医内科专著多以“头痛”为病名，把偏头痛与其它类型的头痛，一并而论，没有进一步的分类，这种把症状作为病名诊断，不利于把握病机、进行治疗、评定疗效和判断预后等．中医学术期刊中，有关偏头痛的研究文章，虽然有明确的西医诊断，但是“理法方药”理论体系缺乏深入而系统的研究。
1 目的
(1)运用中医传统的理论和思维方式，寻求既具有中医特色有能反映偏头痛客观现实的新观点，使偏头痛的“理法方药”，在继承的基础上，得到进一步提高与进步；
(2)在中医病机理论的指导下，对偏头痛的现代医学发病机制，进行整体性探讨，提出发病机制的新假说——5-HT的代谢紊乱是偏头痛的发病基础，皮层扩展性抑制(CSD)是发病的始动因素，脑血管的过度扩张和脑膜无菌性炎症是导致头痛的关键环节。并通过实验的方法为偏头痛发病机制的新假说提供部分依据，同时探讨大川芎丸治疗偏头痛的作用环节。
2 方法与内容
2．1理论研究
采用文献学的方法、结合临床实际，运用分析、归纳等逻辑思维，对偏头痛的“理法方药”体系进行系统研究。具体而言，包括：病因病机的研究、治法探讨、制方规律的研究三部分。
2．2实验研究
以导师王永炎院士关于偏头痛研究中时相问题的论述为指导思想，借鉴国际上通用的用于偏头痛研究的动物模型，以5—HT的代谢紊乱为主线，探讨病理机制间的相互关系，以及大川芎丸的作用环节。包括以下实验内容：(1)通过电生理和激光多普勒技术，探讨高5-HT状态对CSD的影响以及大川芎丸的干预作用；(2)运用微循环的技术和借助电子显微镜，研究低5-HT状态介导的NO超敏现象，并观察大川芎丸的干预作用；(3)运用放射免疫技术，检测5-HT代谢紊乱，对血管活性物质的影响，同时观察大川芎丸的干预作用；(4)采用体外培养的技术与方法，对大鼠脑微血管内皮细胞(rCMEC)进行培养，用于研究5-HT对rCMEC分泌功能的影响，并运用血清药理学的方法，观察大川芎丸含药血清对rCMEC分泌功能的影响。
3 结果
3．1理论研究结果
病因病机：以整体观和恒动观为指导，提出了新的病机认识，认为偏头痛的
三 偏头痛病因病机、治法与方药的相关研究
发病是一个连续的动态演化过程，即肝失疏泄是发病基础，气机失常是始动因素，
气血逆乱、络脉失和为病机关键。并对偏头痛病机研究中涉及的一些概念，进行
了新的诠释，探讨了本病机认识与既往病机认识的关系。
治法探讨：提出调畅气血、和络止痛应为偏头痛的治疗大法，并强调在治疗
中贯彻“截断扭转”思想。
制方规律：首先对历代头痛方剂的用药规律进行了研究，总结出入】首、甘草、
防风、白企等应用频率最高的15味中药，并对这些方剂用药的性味归经进行研究。
其次，在中医传统制方原则的指导下，提出偏头痛的制方规律：强调应用风药；
重视止痛药物的应用；适当选择虫类药；讲究药物的配伍和用量。
3．2实验研究结果
3．2．1 偏头痛发病机制的研究
高5叫T状态，明显增加CSD的反应性，表现在：电生理指标显示，高5叫T
状态，CSD潜伏期和持续时间明显延长，P＜0．005；脑血流量明显降低，P＜0．01。
低5叫T状态，脑血管对NO的反应性增强，表现为：软脑膜微动脉长时间的过度
扩张，P＜0．001；皮层微血管内皮超微结构有微绒毛增多、胞浆内有囊泡小体等。
5叫T代谢紊乱，导致血管活性物质的代谢异常，表现为：高50T状态，ET＋、
NO的血液中浓度增高，P＜0．05和P＜0．001；低5叫T状态，血浆中CRRP、NPY
含量增高，P＜0．05和P＜0．001。本研究成功培养了d肌，观察了5叫 对d饥
的影响，100 p mo儿的 5叫T自促进 BT一1的分泌，P＜ 0．05；10卜 mo几、100卜
mol／L的 5－HT能促进 NO分泌，P＜0．05和 P＜0．001；同时观察了 100 p mol／L的
5叫T对rCMEC分泌功能影响的时效关系，发现ET八在给药6 ／J＼时达高峰，其后
逐渐降低，而NO的分泌在3—12小时呈持续增加。
3．2．2 大）II＃丸的干预作用
大入博丸能降低正常状态的0D的幅度和出现次数，P＜0．05；对于高 5六T
状态导致的持续时间延长有桔抗作用，P＜0．05；对正常状态和高5叫 状态下，
CSD所致的脑血流量降低，都有改善作用，P＜0．05。大刀】苔丸对正常状态下 NO
导致的血管扩张，无于预作用，P＞0．05；但是对低 5叫T状态下，NO导致的血管
过度扩张，可以桔抗，P＜0．05。其还可以改善皮层微血管内皮细胞超微结构的异
常改变。大）II％丸对正常状态下，ET刁、NO、CFRP、NPY的含量有一定影响，但
无统计学意义；对高5叫T状态导致的ET八增高和低5六T状态导致的NPY增高，
有降低作用，P＜0．05。大刀】穹丸的含药血清可以使培养的r删肌分泌m的量降
低，P＜0．05。
4 结论
4．l 偏头痛的中医病机：肝失疏泄是发病基础，气机失常为始动因素，气血逆乱、
络脉失和为病机关键。调畅气血、和络止痛为偏头痛的治
Migraine, one of the most common diseases, is a notable problem that severely disturbs human living quality, which is characterized by its high morbidity and recurring easily. It is generally named as 'headache' by the current monographs of traditional Chinese internal medicine, which confuse migraine with headache of other types and give no further classification. Such diagnostic method regarding symptoms as names do no good to grasping pathogenesis, performing treatment, evaluating curative effects and estimating prognosis of this disease. In the academic journals of Traditional Chinese Medicine (TCM), although the researching articles concerning migraine provide specific western medical diagnosis, there is lack of deep and systematic studies on the "theories, methods, formulae and medicines" system.
1 Objectives
(1) By intrinsic theories and thinking modes of TCM, the researcher seeked a new viewpoint, which reflected both TCM characters and the real condition of migraine to promote the "theories, methods, formulae and medicines" of migraine on successive basis.
(2) Under the instructions of the pathogenesis theories of TCM, the author tried to probe into the holistic pathogenesis of migraine of modern medicine and gave a new hypothesis梩he metabolic disorder of 5-hydroxytryptamine (5-HT) was the pathologic background of migraine. The cortical spreading depression (CSD) was the initiation factor. The excessive cerebrovasodilatation and the aseptic inflammation of meninges played the essential roles during headache. Meanwhile, the authior provided parts of the foundation for the new hypothesis of migraine pathogenesis via experimental methods and discussed the effective pathways of Dachuanxiong Pill as well.
2 Methods and Contents 2.1 Theoretical Study
By philological methods, combining with the clinical practice and using logical thinking modes such as analysis and deduction, the author studied the "theories, methods, formulae and medicines" of migraine systematically. The study included three parts that were embodied as study on etiological factors and pathogenesis, discussion of therapeutics, and rules of formulae as well.
2.2 Experimental Study
Directed by the explanation of phase tissue of migraine put forward by academician WAND Yong-Yang, the author referred to the generally accepted animal models of migraine, mainly concentrated on the metabolic disorder of 5-HT, and discussed the interrelation among different pathogenesis, as well as the active roles of Dachuanxiong Pill.
The experiments were listed as follows.
(1) The influence of hyperserotonin on CSD and the effect of Dachuanxiong Pill were discussed by means of electrophysiology and Laser Doppler.
(2)By microcircular technique and ultrastructural observation, hyposerotonin-induced nitric oxide supersensitivity as well as the intervention effect of Dachuanxiong Pill were studied.
(3) By radio-immunity technique, the influence of inordinate metabolism of serotonin on the active substances of blood vessels as well as the intervention effect of Dachuanxiong Pill were detected.
(4) Rat cerebral microvascular endothelial cell (rCMEC) was cultivated to study the influence of serotonin on the secretive function of rCMEC, and the effect of serum containing Dachuanxiong Pill was observed by seropharmacutiology.
3 Results
3.1 Results of Theoretical Study
Etiological Factors and Pathogenesis: Directed by the concept of Wholism and Permanent movement, the author presented a new hypothesis of pathogenesis of the migraine. The pathogenesis of migraine was thought to be a continuous process of dynamic evolvement under this hypothesis, which included liver's dysfunction of governing free coursing being the pathogenic basis, disturbance of Qi function being the initial factor, derangement of Qi and Blood as well as disharmony of collateral branches of the large channel being the essential factors of the pathogenesis. Meanwhile, some concepts related to the migraine pathogenesis study were reannotated while the relatio
1 目的
(1)运用中医传统的理论和思维方式，寻求既具有中医特色有能反映偏头痛客观现实的新观点，使偏头痛的“理法方药”，在继承的基础上，得到进一步提高与进步；
(2)在中医病机理论的指导下，对偏头痛的现代医学发病机制，进行整体性探讨，提出发病机制的新假说——5-HT的代谢紊乱是偏头痛的发病基础，皮层扩展性抑制(CSD)是发病的始动因素，脑血管的过度扩张和脑膜无菌性炎症是导致头痛的关键环节。并通过实验的方法为偏头痛发病机制的新假说提供部分依据，同时探讨大川芎丸治疗偏头痛的作用环节。
2 方法与内容
2．1理论研究
采用文献学的方法、结合临床实际，运用分析、归纳等逻辑思维，对偏头痛的“理法方药”体系进行系统研究。具体而言，包括：病因病机的研究、治法探讨、制方规律的研究三部分。
2．2实验研究
以导师王永炎院士关于偏头痛研究中时相问题的论述为指导思想，借鉴国际上通用的用于偏头痛研究的动物模型，以5—HT的代谢紊乱为主线，探讨病理机制间的相互关系，以及大川芎丸的作用环节。包括以下实验内容：(1)通过电生理和激光多普勒技术，探讨高5-HT状态对CSD的影响以及大川芎丸的干预作用；(2)运用微循环的技术和借助电子显微镜，研究低5-HT状态介导的NO超敏现象，并观察大川芎丸的干预作用；(3)运用放射免疫技术，检测5-HT代谢紊乱，对血管活性物质的影响，同时观察大川芎丸的干预作用；(4)采用体外培养的技术与方法，对大鼠脑微血管内皮细胞(rCMEC)进行培养，用于研究5-HT对rCMEC分泌功能的影响，并运用血清药理学的方法，观察大川芎丸含药血清对rCMEC分泌功能的影响。
3 结果
3．1理论研究结果
病因病机：以整体观和恒动观为指导，提出了新的病机认识，认为偏头痛的
三 偏头痛病因病机、治法与方药的相关研究
发病是一个连续的动态演化过程，即肝失疏泄是发病基础，气机失常是始动因素，
气血逆乱、络脉失和为病机关键。并对偏头痛病机研究中涉及的一些概念，进行
了新的诠释，探讨了本病机认识与既往病机认识的关系。
治法探讨：提出调畅气血、和络止痛应为偏头痛的治疗大法，并强调在治疗
中贯彻“截断扭转”思想。
制方规律：首先对历代头痛方剂的用药规律进行了研究，总结出入】首、甘草、
防风、白企等应用频率最高的15味中药，并对这些方剂用药的性味归经进行研究。
其次，在中医传统制方原则的指导下，提出偏头痛的制方规律：强调应用风药；
重视止痛药物的应用；适当选择虫类药；讲究药物的配伍和用量。
3．2实验研究结果
3．2．1 偏头痛发病机制的研究
高5叫T状态，明显增加CSD的反应性，表现在：电生理指标显示，高5叫T
状态，CSD潜伏期和持续时间明显延长，P＜0．005；脑血流量明显降低，P＜0．01。
低5叫T状态，脑血管对NO的反应性增强，表现为：软脑膜微动脉长时间的过度
扩张，P＜0．001；皮层微血管内皮超微结构有微绒毛增多、胞浆内有囊泡小体等。
5叫T代谢紊乱，导致血管活性物质的代谢异常，表现为：高50T状态，ET＋、
NO的血液中浓度增高，P＜0．05和P＜0．001；低5叫T状态，血浆中CRRP、NPY
含量增高，P＜0．05和P＜0．001。本研究成功培养了d肌，观察了5叫 对d饥
的影响，100 p mo儿的 5叫T自促进 BT一1的分泌，P＜ 0．05；10卜 mo几、100卜
mol／L的 5－HT能促进 NO分泌，P＜0．05和 P＜0．001；同时观察了 100 p mol／L的
5叫T对rCMEC分泌功能影响的时效关系，发现ET八在给药6 ／J＼时达高峰，其后
逐渐降低，而NO的分泌在3—12小时呈持续增加。
3．2．2 大）II＃丸的干预作用
大入博丸能降低正常状态的0D的幅度和出现次数，P＜0．05；对于高 5六T
状态导致的持续时间延长有桔抗作用，P＜0．05；对正常状态和高5叫 状态下，
CSD所致的脑血流量降低，都有改善作用，P＜0．05。大刀】苔丸对正常状态下 NO
导致的血管扩张，无于预作用，P＞0．05；但是对低 5叫T状态下，NO导致的血管
过度扩张，可以桔抗，P＜0．05。其还可以改善皮层微血管内皮细胞超微结构的异
常改变。大）II％丸对正常状态下，ET刁、NO、CFRP、NPY的含量有一定影响，但
无统计学意义；对高5叫T状态导致的ET八增高和低5六T状态导致的NPY增高，
有降低作用，P＜0．05。大刀】穹丸的含药血清可以使培养的r删肌分泌m的量降
低，P＜0．05。
4 结论
4．l 偏头痛的中医病机：肝失疏泄是发病基础，气机失常为始动因素，气血逆乱、
络脉失和为病机关键。调畅气血、和络止痛为偏头痛的治
Migraine, one of the most common diseases, is a notable problem that severely disturbs human living quality, which is characterized by its high morbidity and recurring easily. It is generally named as 'headache' by the current monographs of traditional Chinese internal medicine, which confuse migraine with headache of other types and give no further classification. Such diagnostic method regarding symptoms as names do no good to grasping pathogenesis, performing treatment, evaluating curative effects and estimating prognosis of this disease. In the academic journals of Traditional Chinese Medicine (TCM), although the researching articles concerning migraine provide specific western medical diagnosis, there is lack of deep and systematic studies on the "theories, methods, formulae and medicines" system.
1 Objectives
(1) By intrinsic theories and thinking modes of TCM, the researcher seeked a new viewpoint, which reflected both TCM characters and the real condition of migraine to promote the "theories, methods, formulae and medicines" of migraine on successive basis.
(2) Under the instructions of the pathogenesis theories of TCM, the author tried to probe into the holistic pathogenesis of migraine of modern medicine and gave a new hypothesis梩he metabolic disorder of 5-hydroxytryptamine (5-HT) was the pathologic background of migraine. The cortical spreading depression (CSD) was the initiation factor. The excessive cerebrovasodilatation and the aseptic inflammation of meninges played the essential roles during headache. Meanwhile, the authior provided parts of the foundation for the new hypothesis of migraine pathogenesis via experimental methods and discussed the effective pathways of Dachuanxiong Pill as well.
2 Methods and Contents 2.1 Theoretical Study
By philological methods, combining with the clinical practice and using logical thinking modes such as analysis and deduction, the author studied the "theories, methods, formulae and medicines" of migraine systematically. The study included three parts that were embodied as study on etiological factors and pathogenesis, discussion of therapeutics, and rules of formulae as well.
2.2 Experimental Study
Directed by the explanation of phase tissue of migraine put forward by academician WAND Yong-Yang, the author referred to the generally accepted animal models of migraine, mainly concentrated on the metabolic disorder of 5-HT, and discussed the interrelation among different pathogenesis, as well as the active roles of Dachuanxiong Pill.
The experiments were listed as follows.
(1) The influence of hyperserotonin on CSD and the effect of Dachuanxiong Pill were discussed by means of electrophysiology and Laser Doppler.
(2)By microcircular technique and ultrastructural observation, hyposerotonin-induced nitric oxide supersensitivity as well as the intervention effect of Dachuanxiong Pill were studied.
(3) By radio-immunity technique, the influence of inordinate metabolism of serotonin on the active substances of blood vessels as well as the intervention effect of Dachuanxiong Pill were detected.
(4) Rat cerebral microvascular endothelial cell (rCMEC) was cultivated to study the influence of serotonin on the secretive function of rCMEC, and the effect of serum containing Dachuanxiong Pill was observed by seropharmacutiology.
3 Results
3.1 Results of Theoretical Study
Etiological Factors and Pathogenesis: Directed by the concept of Wholism and Permanent movement, the author presented a new hypothesis of pathogenesis of the migraine. The pathogenesis of migraine was thought to be a continuous process of dynamic evolvement under this hypothesis, which included liver's dysfunction of governing free coursing being the pathogenic basis, disturbance of Qi function being the initial factor, derangement of Qi and Blood as well as disharmony of collateral branches of the large channel being the essential factors of the pathogenesis. Meanwhile, some concepts related to the migraine pathogenesis study were reannotated while the relatio
引文
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