【作者】 刘敏；

【导师】 王庆国；

【作者基本信息】 北京中医药大学 ， 中医临床基础， 2006， 博士

【摘要】 在我国,出血性中风(intracerebral hemorrhage,ICH)占脑血管病的30%~40%,发病率虽然低于脑缺血(cerebral ischemic,CI),但由于其死亡率和致残率都大大高于CI,因此对人类健康的危害也更为严重。基于以上的原因,对ICH病理生理机制的研究及有效治疗药物的寻找具有十分重要的社会意义与医学价值。到目前为止,现代医学对脑出血病理生理学的认识要比其病理形态和组织学认识肤浅得多,这种局限性直接导致其治疗手段的单一性,因此治疗效果也并不尽人意。相较而言,学者们非常希望能够从中医病因病机理论来认识ICH,在其指导下寻找有效的治疗药物。中医药对出血性中风的认识远可追溯至秦汉时代,而历代医籍皆以中风居杂病之首。从络病理论出发的“毒损脑络”病机假说是本课题的主要理论依据。该理论认为,中风发病是由于毒邪损伤脑络,络脉破损,气血渗灌失常,致脑神失养,神机失守,形成神昏闭厥、半身不遂的病理状态。以此为指导,解毒通络成为治疗ICH的基本大法,而由此衍生出的新清开灵注射液也有望成为有效治疗ICH的方药。目的1探讨从络病理论认识ICH的科学性2部分揭示ICH后相关病机环节的现代生物学基础3从络病理论出发探讨治疗ICH的药物研究思路4对新清开灵注射液治疗ICH的药理学机制进行研究方法1理论研究在回顾历代文献的基础上,从理论上探讨“毒损脑络”病机假说的科学性和解毒通络法治疗ICH的可行性。2实验研究复制胶原酶诱导大鼠ICH模型;用双抗体夹心-酶联免疫吸附试验(ABC-ELISA)法检测脑组织匀浆肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-1β(interleukin-1β,IL-1β)、可溶性细胞间粘附分子(soluble intercellular adhesion molecule-1,sICAM-1)、单核细胞趋化蛋白(monocyte chemo- attractant protein-1,MCP-1)、血清基质金属蛋白酶-9(matrixmetalloproteinase-9,MMP-9)、血浆血小板第八因子相关抗原(von willebrand factor,vWF)含量;用黄嘌呤氧化酶法测定超氧化物歧化酶(superoxide dismutase,SOD),用硫代巴比妥酸法测定丙二醛(malondialdehyde,MDA);用放射免疫法检测血清神经元特异性烯醇化酶(neuron specific enolase,NSE)、血浆内皮素-1(endothelin-1,ET-1)、血栓素B2(TXB2)、6-酮-前列腺素1α(6-keto-PGF1α);采用干湿重法测脑含水量;激光多谱勒法测局部脑血流量(regional cerebral blood flow,rCBF);免疫组织化学法定位细胞间粘附分子(intercellular adhesion molecule-1,ICAM-1)、血管细胞粘附分子(vascular cell adhesion molecule-1,VCAM-1)、E选择素(E-selectin)。结果1理论研究更多还原

【Abstract】 Intracerebral hemorrhage (hemorrhagic stroke, ICH) accounts for 30%~40% in cerebrovascular diseases. Morbidity of ICH is lower than that of cerebral ischemic (IC), however, its mortality and disability rate are both much higher than those of IC. Consequently, ICH has caused great harms to the public health, and it is of medical and societal importance to study the pathophysiology of ICH and seek effective remedies for ICH. Up to now, the advance in pathophysiology of ICH drops far behind the pathology and histology of ICH which results in the oneness of treatment measure directly and the outcome is so disappointing. Comparatively speaking, the scholars hope to study ICH in the view of TCM and to pursue some effective remedies with its guidance. There has been two thousands of years’history of TCM studying stroke since knowledge about stroke was extensively introduced in Internal Classic. Moreover stroke always held the paramount position in many medical literatures in every dynasty. In this paper, the hypothesis of the injury of brain collaterals by toxins coming from the theory of collaterals is the basis of study. This hypothesis is made on the foundation of summarizing the characters of pathological changes and learning by treatment experience of stroke. It considers that stroke comes from the injury of brain collaterals by toxins. The collaterals are broken by the toxins, thus giving rise to something wrong with the nourishing by qi and blood in collaterals, spirit light losing supply and spirit failing to keep to its abode, therefore, the pathological state of clouding reversal and hemiplegia comes into being. Guided by these viewpoints, dispelling the toxins and dredging the brain collaterals are the main treatment method of ICH and New Qingkailing Injection (NQKLI) is expected to be an effective medicine for ICH.Objective:1. To discuss the scientific basis of studying ICH in the view of the theory of collaterals.2. To investigate the materialization about the pathomechanism of ICH in modern biological system.3. To discuss the method of exploring some effective medicine on ICH in the view of the theory of collaterals.4. To study the pharmacological mechanism of action of NQKLI on ICH.更多还原