【作者】 王玥；

【导师】 邓力；

【作者基本信息】 四川大学 ， 药物化学， 2007， 硕士

【摘要】 脑卒中（脑中风）是一组以脑部缺血及出血性损伤症状为主要临床表现的疾病，具有极高的病死率和致残率，近年来，其发病率逐年上升，已经成为全世界第二大死亡原因。脑卒中临床上称为脑梗死，其病理基础是动脉粥样硬化，因此，防止脑梗死形成或缩小梗死体积，恢复脑供血，促进梗死灶周边血液循环就能预防或减少脑卒中的发生。临床上治疗脑卒中的治疗措施很多，如中医、西医等方法，但其疗效都不尽人意。因此，目前脑卒中的治疗更重在预防。近几年来，在脑卒中研究领域兴起的药物预处理方法实质上就是一种预防措施。一些麻醉药预处理的脑保护作用已被研究证实，越来越多的实验证明吸入麻醉药异氟醚（Iso）具有明显的脑保护作用，在围术期预防脑缺血损伤中可能具有重要价值。但是改变剂型的乳化异氟醚是否也有脑缺血耐受作用?为此本实验采用大鼠局灶性脑缺血模型（MCAO），并通过评估缺血再灌注24h的行为学和脑梗死容积，来探讨：（1）乳化异氟醚预处理是否诱导产生脑缺血耐受作用；（2）乳化异氟醚预处理诱导脑缺血耐受的可能机制。实验一：SD大鼠局灶性脑缺血模型的建立。方法：采用大脑中动脉阻闭（middle cerebral artery occlusion，MCAO）模型，将40只雄性SD大鼠随机分成5组（n=8）：A．MCAO 60min组；B．MCAO 120min组；C．MCAO150 min组；D．MCAO180min组；E假手术组（仅分离血管，不留置线拴），观察再灌注后24h动物神经行为学改变及脑梗死容积。结果24h后A-D组神经功能障碍加重，呈递增趋势；24h神经功能损害评分（NDS）E组与A-D组间差异明显（P＜0.05）。再灌注24h脑梗死体积A至D组依次增大，差异明显(（P＜0.05），而E组无梗死灶。A组（132.6±22.1 mm3）梗死容积明显小于B-D组（P＜0.05），B组（216.9±20.3mm3）和C组（223.8±21.7mm3）显著小于D组（296.8±26.6mm3）B与C缺血组无统计学差异。结论：大鼠MCAO 120min为较佳脑缺血模型，并且能很好的重复大脑中动脉阻闭。实验二8％乳化异氟醚预处理对SD大鼠局灶性脑缺血耐受的影响。方法：选择60只雄性SD大鼠，体重250～300 g，随机分成6组，假手术组：仅分离血管，不留置线拴；脑缺血模型组（MO组）：缺血前吸入纯氧30min行MCAO，2h后抽出线栓恢复再灌注；吸入异氟醚组（吸入ISO组）：缺血前吸入0.9％（0.9％约相当于大鼠0.7MAC）异氟醚30min；乳化异氟醚组（乳化ISO组）：缺血前给8％乳化异氟醚17ml（kg·h）^-1；异丙酚组（PRO组）：缺血前给异丙酚15 mg·kg^-1；30％脂肪乳组（30％INT组）：缺血前给30％脂肪乳17ml（kg·h）^-1。所有动物均采用右侧颈动脉MCAO2h，观察再灌注后24h动物神经行为学改变及测量脑梗死容积。结果：结果直肠温度，Pa02，PaC02、血压预处理期间三组无明显差异。术后DNS乳化异氟醚组、吸入异氟醚组和异丙酚组明显低于模型组（P＜0.05）；再灌注24h后脑梗死体积模型组为（227.5±18.15）mm³，乳化异氟醚组，吸入异氟醚组和异丙酚组梗死面积缩小（P＜0.05），但是乳化异氟醚组和吸入异氟醚组没有显著性差异。结论：缺血前给乳化异氟醚对大鼠局灶性脑缺血再灌注损伤产生一定程度的保护作用。更多还原

【Abstract】 The cerebral apoplexy （brain stroke） is a group lacks the blood and thehemorrhage damage symptom take the brain as the main clinicalmanifestation disease, Has the extremely high case fatality rate and crippling rate. In recent years, its disease incidence rate year by year rose, alreadybecame the world second big cause of death. The apoplexy on clinical is called the cerebral infarction, itspathology foundation is the atherosclerosis. Therefore, prevented the infarct volume, restores the brain to donate blood, the promotion stemdead stove peripheral blood circulation can prevent or the reducedapoplexy occurrence. Although many protective treatment measures, such as Chinese medical science and western medicine, against brain ischemia damage have been found, few of them show satisfactory curative effect. Therefore, prevention measures are gradually emphasized in the treatment of brain ischernia. Recently, a lot of studies have focused on preconditioning measures of brain ischemia. Numerous studies have demonstrated the neuropretective effects of isoflurane （Iso）, which indicates Iso may also play an important role in perioperative neurological management. But emulsified isoflurance whether also does have the function in ischemic tolerance in brain. In this study, weevaluated the effects of emulsified isoflurane preconditioning Of neuroprotection against middle cerebral artery occlusion injury. To determine if emulsified isoflurance has protective effect on brain against focal ischemia-reperfusion injury in a rat middle cerebral artery occlusion （MCAO） model.（1） To determine if emulsified isoflurance has protective effect on brain against focal ischemia-reperfusion injury in rats. （2） The Possible mechanism if emulsified isoflurane preconditioning induces ischemic tolerance against brain injury produced by MCAO in rats.Experiment 1:OBJECTIVE To provide reasonable and practicable animal models for clinical cerebral ischernia research. METHOD Middle Cerebral Artery Occlusion （MCAO） were carried out on 40 male S-D rats by suture occlusion via infra artery methods. The animals were divided into 5 groups randomly and equally （n=8）:group A with 60-min MCAO, group B with 120-min MCAO, group C with 150-min MCAO, group D with 180-min MCAO, group D with sham operation. The neurological outcomes were evaluated at 24 h after the reperfusion. After 24h of reperfusion the brain infarct volumes were measured. RESULTS Neurological dysfuctions and brain infarct volumes gradually increased from A to D, E group and A-D group was significance inThe NDS （P＜0.05）. The infarct size A group was lower than B-D group （P＜0.05）. B group, C group was lower than E group （P＜0.05）. but there was no significance in brain infarct volume between group B and C. CONCLUSION 120-min-MCAO rats were perfect cerebral ischernia models.Experiment 2: OBJECTIVE To investigate if Emulsified isoflurane preconditioning induces delayed ischemic tolerance against neuronal damage produced by MCAO in rats. METHOD Sixty male SD rats weighing 250～300 g were anesthetized with intraperitoneal 10%Chloral bydrate 3.5ml/kg. Middle cerebral artery occlusion （MCAO） was performed by surgical exposure of common, internal and external carotid arteries through a longitudinal incision in the neck. A nylon filament （0.20-0.25mm in diameter） with rounded end was inserted into internal carotid carotid artery and threaded cranianlly until resistance was felt. The depth of insertion was about 18-20 mm. The animals were randomly divided intosix equal groups. sham operation group in which caritiod arteries into exposed but no MCAO was performed; ischemia group: the animals inhaled 100% O₂ for 30min before the beginning of MCAO which was maintained for 2h; isoflurane group: 0.9%was inhaled for 30 min before the 2h MCAO. emulsified isoflurance group: 8% emulsified isoflurance 17ml/kg/h was inhaled for 30 min before the 2h MCAO; Propofol group: Propofol 7.5mg/kg was inhaled for 10 min before the 2h MCAO; triglyceride group: 30% triglyceride 17ml/kg/h was inhaled for 30 min before the 2h MCAO;. The neurologic deficit score （NDS） was evaluated 24 h after reperfusion and the infarct volume was calculated at 24 h following reperfusion. RESULTS Rectal temperature, PH, PaO2, PaCO2, blood pressure and blood glucose were controlled and not different among groups during preconditioning. The NDS of isoflurane group, emulsified isoflurance group and Propofol group was lower than ischemia group （P＜0.05）. The infarct size, ischemia group was （227.5±18.15）mm³, isoflurane group, emulsified isoflurance group and Propofol group reduced the infarct size at the end of 24 h reperfusion. （P＜0.05）, but there was no significant difference between emulsified isoflurance group and isoflurane group. CONCLUSIONS Inhalation of 8% emulsified isoflurance can protect brain form focal ischemia reperfusion injury to some extent in rats.更多还原