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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 observe the protective effect of lidocaine on brain injury induced by micro-embolism in rats. Methods Sixty-five male Wistar rats were randomly divided into 5 groups: control group (n = 8): 20% dextran (microsphere carrier) injected into right carotid artery; Two groups (n = 14) were injected with 600 and 900 microspheres respectively. Group 1 (n = 12) and group 2 (n = 13) were injected with 600 and 900 microspheres respectively. In the first 30 min, the lidocaine 1.5 mg / kg loading dose was given intravenously, followed by infusion of 2 mg · kg-1 · h-1 until 1 h after the injection of microspheres. The other groups were given the same amount of saline. Another 4 male Wistar rats were given lidocaine at the above dosage, rate and route for the determination of lidocaine blood concentration. Stroke behavior scores were scored on day 1-7 after injection of microspheres; water maze test (including incubation period and effective search strategy ratio) was performed on days 8-12; after water maze test, 3 rats in each group were taken, Into slices, observe the pathological changes of CA1 neurons. Results Compared with the control group, the stroke scores in both the micro-embolus group and the protective group were increased. After incubation with micro-suppository, the latency was prolonged on the 12th day and the effective search strategy was decreased. Compared with the micro-embolism group 1, After injection of microspheres 3 and 4 days after the stroke score decreased, microspheres microspheres 9 and 12 days after the effective search strategy a higher rate; compared with the two groups of microspheres, the protection of two groups microspheres in the first 1- Stroke behavior scores decreased on the 4th and 6th day. The incubation period was shortened on the 12th day after microspheres injection, and the effective search strategy ratio increased on the 9th and 12th days (P <0.05 or 0.01). Compared with the control group, the number of normal neurons in hippocampal CA1 area in the micro-embolization group decreased, while those in the micro-embolus group and the protective group in the ischemic necrosis group increased (P <0.05 or 0.01) Group (P <0.05). The lidocaine plasma concentration was (2.20 ± 0.18) μg / ml. Conclusion Lidocaine can protect rat brain caused by micro-embolism.