【作者】 孙亚男；

【导师】 邹忆怀；

【作者基本信息】 北京中医药大学 ， 中医内科学， 2012， 博士

【摘要】 本研究是国家973计划《基于临床的内毒损伤络脉的创新病因学研究》的一部分。针对244例中风发病72小时内及14天时病人的实验室指标、以及患者在这两个时点的证候与毒邪的关系,通过临床病例的观察,研究中风病急性期独立于六大证候之外的非特异性症状的相关因素,及治疗前后可能与毒邪相关的病证的变化,希望能在非特异性症状、毒邪相关的证候及实验室指标方面找到一些内在联系,以期运用新的思路和方法,不断补充完善中医辨证论治的内容,体现其动态演变规律,从微观方面揭示中医证候的微观实质,阐明中风病发病机制,从而为该病的中医辨治提供有力的证据。目的：通过临床信息及实验室指标的观察,寻找与中风病急性期“毒损脑络”相关的非特异性症状特点,分析其相关因素及动态演变规律,对比解毒通络法的疗效。方法：收集缺血性中风发病72小时以内的患者,随机分为苦碟子治疗组和血塞通对照组。收集三个时点信息,发病前1周、发病72小时内、发病14天。主要有中西医症状、体征、量表,后两个时点采集实验室指标。六个重点指标有高敏C反应蛋白、白介素-6、氧化低密度脂蛋白、神经元特异性烯醇化酶、基质金属蛋白酶-9、血小板聚集。重点观察先期研究基础的五个非特异性症状(情绪不稳、表情呆滞或反应迟钝、神疲乏力或少气懒言、嗜睡、头昏沉)出现、变化,与中医证候、西医量表、指标的相关和联动性。结果：在发病前一周和发病72小时内头昏沉出现频率最高,其次为神疲乏力或少气懒言、表情呆滞或反应迟钝、情绪不稳,出现频率最少的为嗜睡症状；发病14天时出现频率最高的症状为神疲乏力或少气懒言,其次是头昏沉、情绪不稳、表情呆滞或反应迟钝,出现次数最少的仍为嗜睡症状。发病72小时内Hs-CRP、OX-LDL、IL-6之间有很好的相关性,IL-6与PAGT之间有较好的相关性。发病14天时Hs-CRP与OX-LDL之间有很好的相关性,IL-6与PAGT、NSE与MMP-9之间有较好的相关性。实验室指标Hs-CRP、 OX-LDL及IL-6与NIHSS、MMSE有相关性。非特异性症状成立与否与性别、NIHSS评分及MMSE评分有关。表情呆滞或反应迟钝、神疲乏力或少气懒言、嗜睡、头昏沉无论在发病72小时还是发病14天均与NIHSS和MMSE有明显的相关性。各个非特异性症状与指标存在相关关系,其中神疲乏力或少气懒言、头昏沉、嗜睡这三个非特异性症状与实验室指标之间存在很强的相关性。2个症状个数时与Hs-CRP和IL-6有相关性。非特异性症状总数与NSE、PAGT水平之间有相关性。表情呆滞或反应迟钝、嗜睡、头昏沉这些非特异性症状的变化与实验室指标的变化有一定的动态关系。非特异性症状与各证候分值之间均有相关性。治疗前后两组治疗方案在证候分值的改善上均有优势,苦碟子组侧重于清热解毒活血通络,故对火证症状的改善更明显。对于阴虚症状的改善上要优于血塞通组。对实验室指标MMP-9水平的改善也优于血塞通组。结论：中风病急性期确实存在一组症状,不包含在传统六大证候见症之内,却在疾病发生发展中出现频率很高,可以用“毒损脑络”病因病机阐释。贯穿中风病发展始末,于先兆期和急性期最为明显。本组非特异性症状与炎症反应、神经元损伤等指标之间有着密切关系和联动性,与神经功能缺损、智能评分有很好的相关性。症状出现的个数与中风病兼证的复杂程度有关,与各证候之间有相关性。每个非特异性症状均与实验室指标、NIHSS、MMSE之间表现出很强的关联性。运用解毒通络活血法治疗后,各指标、证候均有好转,且较单纯的活血化瘀法有明显的优势。更多还原

【Abstract】 Based on clinical investigations and laboratory parameters, analyz the relationship between nonspecial symptoms, clinical syndromes and other factors. In order to find characteristics of nonspecial symptoms of "toxin damaging brain collaterals" in acute stage of stroke, we analyze dynamic evolvement rules and therapeutic efficacy of detoxification therapy and blood-activation therapy. Collection of ischemic stroke patients within72hours, randomly divided into Kudiezi group as treatment group and Xuesaitong group as control group. Collected information on the time of1week before strock, within72hours and the14th day after strock, including symptoms especially the nonspecific symptoms, measuring scales and laboratory parameters. The laboratory parameters included High-Sensitivity C-reactive Protein(Hs-CRP), Interleukin-6(IL-6), Oxidized Low-Density Lipoprotein(OX-LDL), Neuron-Specific Enolase(NSE), Matrix Metallopeptidase-9(MMP-9), Platelet aggregation(PAGT). The measuring scales including National Institutes of Health Stroke Scale(NIHSS), and Mini-Mental State Examination(MMSE). The5nonspecific symptoms involving emotional lability, goofy facial expressions, lack of strength, hypersomnia, head giddy.The results indicate that in the week before and72hours head giddy appears highest frequency, followed by lack of strength, goofy facial expressions and emotional lability, hypersomnia appears lowest frequency. The14th day after strock lack of strength appears highest frequency, followed by head giddy, emotional lability, and goofy facial expression, hypersomnia appears the lowest frequency. Within72hours, Hs-CRP, OX-LDL and IL-6showes the best correlation among the6laboratory parameters, IL-6and PAGT indicate better correlation. The14th day after strock Hs-CRP and OX-LDL indicate the best correlation, while IL-6and PAGT, NSE and MMP-9indicate better correlation. Hs-CRP, OX-LDL and IL-6has good correlationship with MIHSS and MMSE. Nonspecific symptoms’establish are relates to gender, NIHSS scores and MMSE scores. Within72hours and the14th day after strock, goofy facial expressions, lack of strength, hypersomnia and head giddy all relate to NIHSS scores and MMSE scores. Each specific symptom correlated with indexes, of which lack of strength, head giddy and hypersomnia, these three nonspecific symptoms have strong correlation to the indexes. There is the correlation between nonspecific symptoms total number and NSE, PAGT level. Changes of goofy facial expression, hypersomnia and head giddy are dynamic relate to laboratory parameters. There is also correlation between nonspecific symptoms and syndrome scores. The two therapeutic schedules all have the preponderance, Kudiezi focus on detoxification, so it improves symptom fire more obviously. Also improves symptom Yin deficiency superior to Xuesaitong group. Kudiezi can reduce MMP-9level.Acute stroke phase do exist a group of symptoms, those symptoms are not included in traditional six syndromes, but it appears high frequency in strock, and "toxin damaging brain collaterals" illness pathologenesis can interpretation. This group of nonspecific symptoms close and dynamic relation with inflammation, neuronal damage, and good correlation with nerve function defect, intelligence score. With detoxification therapy and blood-activation therapy, each index, syndrome, symptoms were well improved.更多还原