【作者】 张云玲；

【导师】 李卫平； 李维祖；

【作者基本信息】 安徽医科大学 ， 药理学， 2008， 硕士

【摘要】 目的:探讨JHS对脑缺血再灌注损伤的保护作用及其可能的作用机制。方法:1.采用小鼠断头实验和常压耐缺氧实验的方法,观察JHS对小鼠脑组织急性缺血、缺氧的保护作用。2.用线栓法制备大鼠局脑缺血再灌注脑损伤模型,观察JHS对缺血再灌注脑损伤大鼠的神经功能缺损评分、血栓形成、血小板聚集、脑梗死体积和脑含水量、脑指数变化的影响;对脑组织MDA、SOD、LDH、LD、NOS含量变化的影响;对脑组织肿瘤坏死因子-α(TNF-α)和Caspase-3的表达及脑组织病理形态学的影响。3.采用超声血流计观察JHS对家兔脑血流和脑血管阻力变化的影响;采用BL- 420E生物机能实验系统观察JHS对家兔血压的影响。4.采用胎鼠海马神经元体外培养的方法,制备神经细胞缺氧复氧损伤模型,观察JHS对神经细胞的活力、凋亡程度及对胞质游离钙离子浓度的影响。结果:1. JHS能够延长小鼠断头后张口喘气时间和常压耐缺氧的存活时间。2. JHS对局脑缺血再灌注后8h和22h神经功能缺损评分有一定的恢复作用;JHS能够降低MCAO再灌注22h大鼠的脑梗塞体积;JHS对MCAO再灌注大鼠体外血栓形成长度、血栓湿重、血栓干重有降低作用,对血小板聚集有一定的抑制作用;JHS能够降低MCAO再灌注大鼠脑组织升高的MDA含量、LD含量,提高SOD、LDH活性,抑制NOS活性;JHS对MCAO再灌注22h大鼠增加的脑含水量和脑指数有一定的降低作用,JHS可以减轻局脑缺血再灌注大鼠脑组织病理损害;JHS能够抑制局脑缺血再灌注大鼠脑组织TNF-α和Caspase-3的表达。3. JHS对家兔脑血流量有一定的增加作用,对脑血管阻力有一定的降低作用,但对家兔给药后各时点血压变化无明显影响。4. JHS可以明显提高缺氧复氧后海马神经元的活力和抑制海马神经元的凋亡、使海马神经元升高的胞浆钙离子浓度降低。结论: JHS对脑缺血再灌注损伤有一定的保护作用,其作用机制可能与其对缺血再灌注脑损伤的动物具有抑制血小板的聚集、血栓的形成、防治自由基的损伤、降低增加的胞浆钙离子浓度、增加脑血流量和抑制TNF-α的表达及抑制细胞的凋亡等作用有关。更多还原

【Abstract】 Objective To study the protective effects and mechanisms of JHS on cerebral ischemia-reperfusion injury .Methods1. The experiments of quick decapitation and anoxia under normal pressure model in mice were used to study the effects of JHS on acute cerebral ischemia and anoxia.2. The focal cerebral ischemia-reperfusion model was built by the suture method for middle cerebral artery occlusion (MCAO) in rats. The model was made to observe the effects of JHS on neurological function score, infarction volume of the brain, thrombogenesis in vitro, platelet aggregation, water content and cerebral index; To investigate the activity of SOD, LDH, NOS and the content of MDA, LD in brain tissue; TNF-αand Caspase-3 were observed by immunohistochemistry and brain pathology was studied with morphological method.3. The effects of JHS on cerebral blood flow(CBF), cerebral vascular resistance(CVR) were observed by Ultrasonic Doppler Instrument, blood pressure and heart rate were detected in anaesthesia-rabbit by BL-420E system.4. An anoxia-reoxygenation injured model was established by using primary cultured hippocampal neurons in vitro, the model was made to observe the effects of JHS on activity, the level of apoptosis and the intracellular calcium concentration of hippocampal neuron . Results1. JHS could prolong the gasping time of mice after quick decapitation and survival time of anoxic mice.2. Compared with model group, JHS could decrease the neurological function score after focal cerebral ischemia reperfusion at 8h and 22h; JHS could decrease the infarction volume of brain , the length , wet weight, dry weight of thromb and inhibit platelet aggregation in rats after focal cerebral ischemia reperfusion; JHS could reduce the brain edema, brain index and obviously relieve histopathologic injury in brain tissue; The activity of SOD, LDH of brain were increased, while MDA, LD, NOS decreased after treated by JHS; the expression of TNF-αand Caspase-3 could be inhibited by JHS on focal cerebral ischemia-reperfusion rats.3. JHS could increase the cerebral blood flow and decrease the cerebral vascular resistance in anaesthesia rabbits . There is no obviouse influence on blood pressure after administration of JHS.4. JHS could significantly improve neuronal viability after anoxia-reoxygenation injury of hippocampal neurons, inhibit the apoptosis of the neurons and decrease the intracellular calcium concentration of hippocampal neuron.Conclusion JHS took protective effects on cerebral ischemia-reperfusion injuries. The role of thrombolysis, antioxidation, calcium antagonism, inhibition of platelet aggregation and apoptosis, inhibition the expression of TNF-αand Caspase-3 might contribute to its neuro protective effect.更多还原