摘要
目的观察利多卡因对大鼠微栓栓塞致脑损伤的保护作用。方法雄性Wistar大鼠65 只,随机分为5组,对照组(n=8):经右侧颈动脉注射20%葡聚糖(微球载体);微栓1组(n=14)及微栓2组(n=14),分别注射600和900个微球;保护1组(n=12)和保护2组(n=13),分别注射600和900个微球,并于注射微球前30 min经股静脉注射利多卡因1.5 mg/kg负荷剂量,继以2 mg·kg-1·h-1 持续输注直至注射微球后1 h,其余组给予等量生理盐水。另取雄性Wistar大鼠4只,按上述剂量、速率及途径给予利多卡因,用于测定利多卡因血药浓度。注射微球后第1-7天进行脑卒中行为评分; 第8-12天进行水迷宫试验(包括潜伏期和有效搜索策略比率);水迷宫试验后,每组取3只大鼠,取海马制成切片,观察CA1区神经元的病理变化。结果与对照组比较,微栓组和保护组脑卒中行为评分均升高;微栓2组注射微球后第12天潜伏期延长,有效搜索策略比率降低;与微栓1组比较,保护1组在注射微球后第3、4天脑卒中行为评分降低,注射微球后第9、12天有效搜索策略比率较高; 与微栓2组比较,保护2组在注射微球后第1-4、6天脑卒中行为评分降低,注射微球后第12天潜伏期缩短,第9、12天有效搜索策略比率升高(P<0.05或0.01)。与对照组比较,微栓组栓塞侧海马CA1 区的正常神经元计数减少;缺血坏死神经元计数微栓组和保护组均升高(P<0.05或0.01),但保护组少于微栓组(P<0.05)。利多卡因血药浓度为(2.20±0.18)μg/ml。结论利多卡因对大鼠微栓栓塞引起的脑损伤有一定的保护作用。
Objective To investigate if lidocaine can alleviate the behavioral disorder, learning and memory dysfunction and neuropathological lesions induced by cerebral microsphere embolism. Methods Sixty-five healthy male Wistar rats weighing 210-270 g were randomly divided into 5 groups： 2 microsphere groups （ n = 14 each）, 2 lidocaine pretreatment groups （n = 12, 13） and control group （n = 8）. The animals were anesthetized with isoflurane, 60% nitrous oxide and O2. In the microsphere groups 600 or 900 microspheres were injected into right internal carotid artery. In the lidocaine pretreatment groups a bolus of lidocaine 1.5 mg·kg^-1 was given via femoral vein 30 min before microsphere injection followed by lidocaine infusion at 2 mg·kg^-1·h^-1 until lh after microsphere injection. In control group vehicle without microsphere was injected. The behavior score was recorded every day from the 1st to 7th day after microsphere injection. The Morris water maze test was performed 3 times a day starting from the 8th to 12th day after microsphere injection. The animals were sacrificed after the last water maze test. Brains were removed for microscopic examination of the hippocampus CA1 region. Results （1） The behavioral scores （0 = no typical signs, 9 = worst results） decreased with time after embolism in all groups and were significantly higher in the microsphere and lidocaine groups than in control group. They were significantly higher in microsphere group 2 than in microsphere group 1 and the two lidocaine groups （P 〈 0.05, 0.01 ）. （2） In water maze test the latency periods shortened with time in all groups and were significantly shorter in lidocaine group 2 than in microsphere group 2 （P 〈 0.01）. The ratio of effective search strategy increased with time in all groups and was significantly higher in the lidocaine groups than in the corresponding microsphere groups （ P 〈 0.05, 0.01）. （3） The number of ischemic dead neurons in hippocampus CAI region was significantly larger in
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2005年第7期527-531,共5页
Chinese Journal of Anesthesiology
基金
教育部留学回国人员科研启动基金资助项目(99-1-264国家自然科学基金资助项目(30371369)
