黄芪桂枝五物颗粒对实验性脑缺血的保护作用及机理初探

【作者】 庄严；

【导师】 孙建宁；

【作者基本信息】 北京中医药大学 ， 中西医结合基础， 2004， 硕士

【摘要】 缺血性脑血管病分为短暂脑缺血发作和脑梗死(包括脑血栓形成,脑栓塞,腔隙性梗死,血管性痴呆),已在中老年疾病中占第一位。由于有广泛的发病率,致残率,致死率,影响病人的日常生活,并造成家庭和社会的负担。所以该疾病越来越受到各方面的重视。 现阶段中医防治缺血性脑血管病工作已有显著进展: 用现代医学理论来阐明中医药治疗机理,可以使临床疗效提高,伴随理论实验研究的进一步深入,中医药的治疗更加客观化和标准化。 缺血性脑血管病属中医中风范畴,近代通过对活血化瘀药及补益药的作用研究,筛选出许多中药及方剂,并确定有效部位或成分。我们选用大鼠大脑中动脉血栓形成模型、大鼠多发脑梗塞模型,观察HQGZWWKL对缺血脑组织的保护作用;并通过其对血小板聚集、对凝血功能的影响和对t-PA含量的影响,初步分析HQGZWWKL的作用机制,为其临床提供可靠的实验依据。1.HQGZWWKL 对大脑中动脉血栓形成模型(Middle Cerebral Artery Thrombosis,MCAT)大鼠的保护作用 实验采用Fecl3建立大脑中动脉血栓形成模型。在术后不同时间(6h,24h)用评分法来测定大鼠神经症状。结果表明HQGZWWKL0.828g/kg、0.414g/kg、0.207g/kg可减轻MCAT大鼠的神经症状(与模型组相比 P<0.01),并有一定的量效关系。TTC染色测定其梗塞范围,表明HQGZWWKL0.828g/kg、0.414g/kg、0.207g/kg可明显缩小大鼠的梗塞范围(与模型组比P<0.01)。脑组织病理形态学结果:模型组大鼠损伤侧皮质可见大量变性神经元,核固缩、胞质溶解。HQGZWWKL0.828、0.414g/kg组大鼠损伤侧皮质可见少量变性神经元,突起延长;0.207g/kg组大鼠损伤侧皮质仍见大量变性神经元,在变性神经元中散在有正常神经元。提示本药对大鼠实验性脑缺血具有保护作用。2.HQGZWWKL对大鼠多发脑梗塞模型(MCI)脑组织生化指标的影响 将3%血块生理盐水混悬液注入颈内动脉,造成多发脑梗塞模型。结果表明,模型组MDA、乳酸的升高, SOD 的活性下降。 HQGZWWKL0.828g/kg、 0.414g/kg、 0.207g/kg可抑制MCI大鼠所致 MDA、乳酸的升高,并能提高 SOD 的活性,差异显著(与模型组相比P<0.01,P<0.05)。<WP=4>2 黄芪桂枝五物颗粒对实验验性脑缺血的保护作用及作用机理初探3.HQGZWWKL对凝血-纤溶系统影响 HQGZWWKL0.828g/kg、0.414g/kg、0.207g/kg 连续 3 天灌胃给药,对ADP诱导的血小板聚集均表现出明显的抑制作用(与对照组相比P<0.01,P<0.05),这表明药物具有抗血小板血栓形成的作用。HQGZWWKL 0.414g/kg 可明显延长凝血时间(与对照组相比P<0.05),降低凝血强度(与对照组相比P<0.05),HQGZWWKL0.828g/kg、0.414g/kg、0.207g/kg对凝血速率的也有抑制作用(与对照组相比P<0.05)。HQGZWWKL0.828g/kg、0.414g/kg可明显增加MCAT大鼠血浆t-PA 活性(与模型组相比较P<0.05)。 以上实验表明,HQGZWWKL可减轻实验性脑缺血大鼠脑病理组织学的损伤,减小梗塞范围,减轻神经症状,对实验性脑缺血有保护作用。可抑制乳酸和MDA,增加SOD的活性,抑制血小板聚集、延长凝血时间、使血浆t-PA 含量增多,这可能是它治疗缺血性脑损伤的机制之一。更多还原

【Abstract】 Stroke,including hemorrhagic and ischemic stroke,is a common disease in middle andold aged people. The disease incidence of ischemic stroke is higher than hemorrhagic stroke.Epidemiological surgery showed that the one thirdof patients died after the onset of stroke andthe rest lost their working and even living ability because of the hemiplegia,apraxia,etc.Therefore,it is anurgent task to further definite the pathophysiological mechanism of cerebralischemia and to develop effective agent of preventing and treating ischemic stroke. Previous studies have demonstrated that energy metabolism dysfunction of brain issuefollowing cerebral ischemic injury,caused massive free radicals producing,[Ca2+]i rising,and neurons apoptosis.In addition,platelet activation and changes of hemorheology were alsorelated with cerebral ischemic injury. Furthermore,above-mentioned factors interacted andcaused the secondary injury after cerebral ischemia. Huang Gui Wu Wu Ke Li (HQGZWWKL) is an experientia1 prescription used forstroke. In this paper, the author investigated the effect of HQGZWWKL on experimenta1cerebral ischemic damage models: middle cerebral artery thrombosis (MCAT) which ismade by adding FeCl3 to the surface of the right middle cerebral artery (MCA) for 30 minand multiple cerebral infarction (MCI) in rats.The resu1ts are as fo11ows: 1. Protective effect of HQGZWWKL on ischemia injury rats subjected to middlecerebralarterythrombosis (MCAT) After MCAT in rats, brain infarction and neurological symptoms occurred. Theprotective effects of HQGZWWKL on rats subjected to MCAT induced with FeCl3 wereobserved in the experiment. Results showed that 0.828g·kg-1 and 0.414mg·kg-1 reducedinfarctsize(IS) by33.05%and29.76%respectively (P<0.05,P<0.0l, comparedwithvehicle). This suggested that HQGZWWKL had the treatment effect on cerebral ischemicinjury. Pathology and histology research show that HQGZWWKL could significantlyalleviatetheischemic. 2.The effect of HQGZWWKL on brain issue free radical mechanism of multiple cerebral infarction (MCI) After multiple cerebral infarction(MCI),massive free radicals produced,its scavengerenzymes were consumed excessively,and the balance of free radical mechanism wasdamaged,the secondary injury of brain issue occurred. The effects of HQGZWWKLon freeradical metabolism in the brain issue of MCI rats and the effect of HQGZWWKL on it wasstudied in the experiment. Result showed HQGZWWKL 0.828g/kg and 0.414g/kg cou1dpromoteSODactivity (P<0.05, P<0.0l, compared with vehicle), reduce MDA and lacontent(P<0.05,compared with vehicle)in ischemic hemisphere of MCI rat’s brain issue.Therefore,the protective effect of HQGZWWKL on ischemic injury may be related to<WP=6>balancing free radicals mechanism of brain issue. 3.The effect of HQGZWWKL on fibrinolysis system and coagulation system After cerebral ischemia, platelet aggregated to form microthrombus to exacerbatedmalfunction of focal microcirculation in brain issue. The effects of HQGZWWKLadministered in vivo and in vitro on platelet aggregation were studied in the experiment.Results suggested that HQGZWWKL0.828g/kg and 0.414g/kg inhibited platelet aggregationof normal rats induced with ADP (P<0.05, P<0.0l, compared with normal). HQGZWWKL 0.828g/kg and 0.414g/kg could obviously prolong the coagulation time(CT) and the rate of coagulation time of normalrat (P<0.05, P<0.0l, compared withnormal). HQGZWWKL 0.828g/kg and 0.414g/kg could significantly raise the decrease ofactivityoft-PA (P<0.05, comparedwithvehicle). The resu1t indicated that HQGZWWKL cou1d protect the brain against ishemicdamage. It suggests that the protective effect were probab1y related to promotion of activity ofSOD, reduce and la content, inhibition of platelet aggregation, prolong the CT and raisethe activity of t-PA of MCAT rat.更多还原