【作者】 李俊哲；

【导师】 黄衍寿；

【作者基本信息】 广州中医药大学 ， 中医内科学， 2010， 博士

【摘要】 目的：通过实验与临床研究,阐明芎冰喷雾剂对急性缺血性脑卒中的疗效及其作用机理,通过芎冰普通制剂与纳米制剂的药效对比,予纳米制剂客观评价,并为芎冰喷雾剂的推广应用提供科学的理论和实践依据。方法：(一)实验研究：采用线栓法制作大鼠大脑中动脉缺血再灌注损伤模型,并采用神经功能评分、TTC染色、实时荧光定量-PCR、HE染色后光镜下观察显微结构及检测血清中炎症因子等方法,分别对假手术组、缺血再灌注组(模型组)、尼莫通组、普通芎冰喷雾剂、芎冰纳米喷雾剂(高、低剂量)组的缺血后大鼠神经功能缺失征象、再灌注后缺血侧脑梗塞体积,Caspase-3. AQP4基因表达的定量,TNF-α、IL-1β的含量进行观测和比较。(二)临床研究：按照随机对照原则,将60例急性缺血性脑卒中患者分为治疗组(常规西药加用芎冰喷雾剂)和常规西药对照组,疗程均为两周,重点观察治疗前后患者的中医证候评分、神经功能缺损程度评分。结果：(一)实验研究：普通制剂组、尼莫通组、纳米制剂高剂组均能明显改善脑缺血大鼠的神经功能缺损程度,减少缺血体积,下调Caspase-3、AQP4基因的表达,减轻缺血缺氧缺血的病理改变,有效抑制TNF-α、IL-1β的升高,其中三种制剂的疗效大致相似,而部分指标则提示普通芎冰喷雾剂、芎冰纳米制剂高剂量的效果更优于尼莫通。(二)临床研究：治疗组中医证候积分及神经功能缺损程度积分明显优于对照组,但中医证候疗效与对照组尚无统计学差别。安全性研究证明芎冰纳米喷雾剂无明显肝肾毒性及严重不良反应。结论：芎冰喷雾剂通过抗细胞凋亡,减轻缺血后脑水肿,抑制炎症反应等而发挥对抗缺血再灌注损伤的作用,具有显著的脑保护作用,纳米制剂有其优越之处,但仍有待改进。临床观察表明芎冰喷雾剂能改善急性缺血性中风患者神经功能缺损症状,是治疗急性缺血性脑卒中的理想药物之一,值得推广应用。更多还原

【Abstract】 Objective:To investigate the effect and mechanism of Xiongbing spray in treating acute cerebral ischemic stroke by experimental and clinical study, objective evaluate the effect of nanometer praeparatum by comparing to the common praeparatum, and provide the bases for using Xiongbing spray in clinical practice.Method:Animal experimental study:seventy-eight SD rats were randomly divided into six groups:the pseudo operated group, the model group (operated), Nimoldipine group, Common praeparatum group, and nanometer praeparatum groups (treated with high and low dose respective). The rats cerebral ischemic stroke model were subjected to focal ischemic by middle cerebral artery occlusion(MCAO)using intraluminal thread. The neurologic impairment scoring, cerebral ischemic area measured by TTC-staining, the quantity of gene expression by Caspase-3 and AQP4 in ischemic brain tissue, the result of pathology photograph, and the level of TNF-αand IL-1βin the peripheral blood were observed and compared between groups.clinical study:sixty patients were randomly divided into therapy group (treated with Xiongbing spray and general westen medicine) and controlled group(only using general westen medicine), the treatment period was two weeks. The neurologic impairment scoring, clinical effect of TCM syndrome were observed before and after treatment, as well as the security of Xiongbing spray.Result:Animal experimental study:Common praeparatum, nanometer praeparatum with high dose and nimoldipine could ameliorate the scorings of neural deficit of cerebral ischemic stroke rats, reduce cerebral ischemic area measured by TTC-staining, decrease quantity of gene expression by Caspase-3 and AQP4 in ischemic brain tissue, active suppress the increase of TNF-αand IL-1βin the peripheral blood, significant reductions of nerval tissue damage were also found in the three groups by pathology photograph. Experimental result show that therapeutic effect of three kinds of praeparatum above-mentioned is similar on the whole, while part of it manifest common praeparatum and high dose nanometer praeparatum surpass nimoldipine.clinical study:the ameliorations of the scoring of neural deficit in Xiongbing spray group were predominant compared with controlled group, the same case could be seen in the scoring of TCM syndrome while curative effect of TCM syndrome without statistics difference between groups. The function of liver and renal, blood general measuring were normal before and after treatment,there was no severe adverse reactions in patients caused by Xiongbing spray.Conclusions:Xiongbing spray has remarkable protective effect against focal brain damage induced by occlusion-reperfusion, which can inhibiting neural cells apotosis, reduce ischemic brain edema and controling Inflammatory reaction. nanometer praeparatum has its own predominance although need to improve. Xiongbing spray could ameliorate the scorings of neural deficit in patients, We can conclude that Xiongbing spray be one of ideal medicines for acute cerebral ischemic stroke.更多还原