【作者】 刘亚敏；

【导师】 彭胜权；

【作者基本信息】 广州中医药大学 ， 中医临床基础， 2002， 博士

【摘要】 随着急性缺血性中风(AIS)的发病率的逐年增高，寻找有效防治该病的措施，已成为世界研究的热点之一。中医药对AIS的治疗具有一定的优势，其药理作用的多靶点、多途径性引起了医学界的广泛重视。本课题基于导师彭胜权教授长期的临床经验和以往的研究为基础，认为气血逆乱，脑窍闭阻是中风的主要病理环节，芳香开窍法是急性缺血性中风的基本治则，并以中医理论及现代医学对缺血性中风的机理研究为出发点，从理论、临床、实验三个方面对芳香开窍法治疗AIS及其脑保护作用进行了研究。 1 文献与理论研究 1．1 有文献提到运用醒脑开窍针刺法治疗中风取得了较好的临床疗效，但未见关于以麝香、冰片为药对的芳香开窍法作为主要治法用于AIS的治疗。 1．2 现代医学对AIS的发病机制做了深入的研究，但有效的治疗手段仍然缺乏，目前主要集中在溶栓疗法和脑保护疗法，其中溶栓疗法受时间窗的限制以及容易导致出血和再灌注损伤而被公认具有一定的危险性，各种脑保护剂因其作用较为单一，副作用大，而不能广泛使用。此外，血脑屏障的存在限制了脑保护药物进入脑组织而影响疗效仍是困扰临床的主要问题。 1．3 芳香开窍法对神经系统疾病具有良好的疗效，其药理作用主要有：迅速透过血脑屏障并直接作用于中枢神经系统；中枢兴奋和中枢抑制作用；抗炎作用；抗脑缺血、缺氧及脑水肿的作用。 1．4 对开窍法在中风治疗中的应用进行了回顾和思考，认为脑主神明，其“清灵之窍”易闭塞；指出对AIS的治疗，必须把握脑窍闭阻的主要病理机制，不可拘泥于开窍法或开窍药的使用禁忌，从而进一步确立了开窍法治疗中风的理论基础。 2 临床研究 2．1目的 观察芳香开窍法治疗；急性缺血性中风的疗效，评价其临床应用价值。 2．2 方法 44例AIS患者随机分为治疗组和对照组。治疗组20例采用辨证治疗加芳香开 芳香开疼法对凡性缺血性申风的脑保护作用研取窍药“通窍胶囊”，对照组24例仅中医辨证治疗，两周为一疗程。从两组总疗效。神经功能缺损评分、72小时意识障碍的改善以及两组起效时间的比较来评价芳香开窍法的临床疗效，并对“通窍胶囊”的用药安全性进行了观察。2．3 结果 两组的中医临床辨证分型一。，以痰瘀阻络型最多，其次为气虚血瘀型，阴虚阳亢型，而风火上扰型最少。这在某种程度上，反映了岭南人群体质以痰湿、气阴两虚为主的特点；两组的总有效率：治疗组为 95．0％，对照组为 91．6％，但差异无显著性意义（AO．05），而两组的愈显率差异有显著性意义（KO．05），治疗组优于对照组。72个时意识障碍的改善：治疗组为80．0％，对照组为35．3％，差别具有显著性意义仰O．05厂 两组起效时间：治疗组对＊ 患者的平均起效时间是25．4小时，而对照组为44．3小时，两组差别具有显著性意义（RO．05）；对于治疗组中无意识障碍的患者，配合使用芳香开窍药亦取得良好疗效，并未见病情加重、耗伤元气的表现；芳香开窍药在常规剂量的使用下，无明显的毒副作用和肝肾损害。2．4 结论 脑窍闭阻是急性缺血性中风的重要病理机制，芳香开窍法是其基本的治则，在辨证基础上配合芳香开窍法能明显提高急性缺血．性中风的临床疗效，尤其在改善病人的意识障碍和提高药物的起效时间上具有一定的优势。3 实验研究3．1 目的 通过对全脑缺血再灌注大鼠模型的实验观察，从多角度探讨芳香开窍法对缺血再灌注大鼠的脑保护作用，为临床推广和运用芳香开窍法提供实验依据。3．2 方法 采用Pulsinelli的4，用 tig建立大鼠全脑缺血再灌注模型，设假手术组、模型组。中药组（魔香、冰片悬浊液）及尼莫通组。模型组、中药组及尼莫通组阻断大鼠4血管45min，再灌注6h。假手术组仅分离肌肉。血管，不夹闭血管，余手术过程相同。采用干湿法测定脑含水量并通过光境观察脑组织水肿情况；黄瞟吟氧化酶法测定SOD（超氧化物歧化酶）、T13A法测定MDA（丙h醛＼ 高效液相色谱前衍生法测定氨基酸类神经递质；硝酸还原酶法测定NO（一氧化氮）；免疫组化染色法检测内皮细胞型和诱导型一氧化氮合酶（eNOS和 iNOS）表达及细胞间粘附分子一二（ICAM－1）表达；RT－PCR技术检测脑组织水通道蛋臼－4 mRNA（AQI’－4 mRNA）及白介素一16mRNA （IL－ie mRNA）表达。3．3 结果 芳香开窍药（蜃香、冰片）具有以下作用：3．3．1 减少缺血再灌注后的脑水肿，使缺血脑组织显微结构趋于正常； 2 务导开蚜法对尾性缺血性中凡的脑保护作用研兜 2．3．2 扣喇A阶心。圳A的表达，减少脑水肌 3．3．3 降低MDA的含量，提高脑组织SOD的活性，具有抗自山基损伤的作用； 3．3．4 降低I’J冬氨酸M叩）的含量和提高v－氨基丁酸KABA人 It氨酸uly） 的水平，对中枢神经系统具有兴奋和抑制的双?更多还原

【Abstract】 As its incidence grows every year, seeking an effective prevention and cure of acute ischemic stroke (AIS) is becoming one of the world’ s heated researches today. The traditional Chinese medicine (TCM) has some advantage over other drugs in the treatment of A1S, and has aroused broad interest of the medical circle with i’;s multi targets of pharmacological action and multi-therapeutic ways.This paper, based on Prof. Peng Shengquan’ s long clinical experience and the past relevant researches , presents the theory that the brain is in charge of spirit and mind , that disorder in qi and blood and obstruction in the brain orifice are the leading causes for AIS, and that resuscitation-inducing therapy with fragrant drugs(RlTFD) is the basic principle of treatment in the cure of stroke at its acute stage, and starting from the research into the mechanism of ischemic stroke in the traditional Chinese medicine( TCM) theory and the modern medicine, makes a theoretical, cl inical and experimental exploration of the treatment of AIS with RLTFD and its brain protecting effect.Documents and theoretical study1. Some documents mention brain waki.ng-up acupuncture t.heray used in the treatment of ALS, but nothing about the use of resuscitation-inducing therapy with musk and bomeal as a pair of fragrant drugs as the main therapy.2. Effective therapy of wind stroke is still lacking though in the past years, there have been in-depth researches into the pathological mechanism of AIS in the modern medicine. The current focused therapeutic treatments are thrombolysis therapy and brain protecting therapy, the former is generally thought to be dangerous to some degree for the reason that it is restricted by time window and easily leads to hemorrhage and reperfusion injury. Brainprotecting therapy has received great attention of the medical world, and yet is not widely used due to the 1 imited curative effect and big side-effect of different, brain protecting drugs and their difficulty to penetrate blood brain barrier.3.R1TFD has a good curative effect on the diseases of the central nervous system. Its pharmacological effects are: fast panetration through blood brain barrier and hence direct action to the central nervous system;central excitement and central inhibition, anti-inflammation, protection of the brain that has ischemia , anoxa and edema.4. The rethinking of the use of R1TFD in the treatment of stroke holds that the brain is in charge of spirit and mind and its " mind’ s orifice" is liable to obstruction, that in the treatment it is necessary to make sure what is the leading pathological mechanism of the obstruction of the brain orifice, and that the contraindication against the use of R1TFD and of drugs for inducing resuscitatin should not be rigidly stuck to. The rethinking further establishes the theoretica foundation of resuscitation-inducing therapy with fragrant drugs in MS care.Clinical researchObjective: To observe and test the clinical curative effect of RiTFD on AIS and evaluate its clinical and applicative value.Method: 44 AIS patients were randomly divided into treatment group, and control group. The treatment group, consisting of 20 patients, were, on the basis of differentia! diagnosis, additionally treated with the drug for inducing resuscitation "tongqiao capsule" and the control group, made up of 24 patients, received only TCM treatment based on differential diagnosis; each treatment course was two weeks long. The cl inical curative effect was evaluated in the light of the total curative effect of the two groups, the score of nervous function defect, the curative effect on 72 hours’ disturbance of consciousness and the comparison of the numbers of hours the two groups’ treatment needed to produce initial effect. And the safety of the application of "tongqiao capsule" was also observed. Results: l.As typed in the light of differential diagnosis, of the two groups, thepatients with stagnation of phlegm and blood in collaterals came out first in number, followed by those with更多还原