利多卡因对慢性应激小鼠学习记忆功能障碍及神经病理变化的影响

目的观察利多卡因对慢性应激致小鼠学习记忆功能障碍和海马神经病理变化的影响。方法32只雄性昆明小鼠随机分为生理盐水对照组、利多卡因对照组、慢性应激组和利多卡因治疗组,每组8只。利多卡因对照组和利多卡因治疗组每日腹腔内注射利多卡因,其他组给予生理盐水。慢性应激组和利多卡因治疗组每日进行复合应激刺激,连续21d,其他组不接受应激刺激。然后对小鼠进行Morris水迷宫测试;测试结束后进行灌注固定,取小鼠脑组织行尼氏染色,观察海马CA3区神经元的病理变化。结果（1）水迷宫测试：各组动物的潜伏期均随测试天数增多而缩短。测试第5天时的潜伏期慢性应激组明显长于两个对照组（均为P〈0．01）;利多卡因治疗组明显短于慢性应激组（P〈0．05）,而与两个对照组相比差异均无统计学意义。除慢性应激组外,各组动物的有效搜索策略百分比均随测试天数增加而升高,测试第5天时明显高于第1天（两个对照组均为P〈0．05,利多卡因治疗组为P〈0．01）。（2）海马CA3区神经病理检查：锥体细胞计数和尼氏体平均吸光度值慢性应激组均明显少于或低于两个对照组（均为P〈0．01）;利多卡因治疗组明显多于或高于慢性应激组（均为P〈0．01）,而与两个对照组相比差异均无统计学意义。结论慢性应激导致小鼠学习记忆功能障碍和海马CA3区神经元损害。利多卡因明显减轻了慢性应激引起的小鼠学习记忆功能障碍和海马CA3区神经元损害。

Effects of lidocaine on learning and memory dysfunction as well neuropathologic change induced by chronic stress: experiment with mice

OBJECTIVE: To explore the effects of lidocaine on the learning and memory dysfunction as well neuropathologic change induced by chronic stress. METHODS: Thirty-two mice were randomly divided into 4 equal groups: normal saline (NS) control group, undergoing intraperitoneal injection of NS daily for 21 days; lidocaine control group, undergoing intraperitoneal injection of lidocaine daily; chronic stress group, undergoing intraperitoneal injection of NS daily and then receiving the stimulation of different stressors alternatively; and lidocaine treatment group, undergoing intraperitoneal injection of lidocaine daily and then receiving the stimulation of different stressors alternatively. The body weight was measured every day. Then there was 1-day rest. On the 23 rd day water maze pretest was performed and since the day 24 water maze test was begun 3 times a day for 5 days. The orbit of swimming was monitored and the time used to find the platform (latency period) and the rate of effective search strategy were recorded. After the test perfusion and fixation of the brain was conducted. Coronal sections were made to observe the neuropathology of the CA3 region of the hippocampus. RESULTS: The body weight did not change significantly in all groups. The latency period was shortened along with the time in all groups. On day 5 the latency period of the lidocaine treatment group was 12 +/- 4 seconds, significantly shorter than that of the chronic stress group (25 +/- 10) s, P < 0.05] and not significantly different from those of the 2 control groups, and that of the chronic stress group was significantly longer than those of the 2 control groups (all < 0.01). The rate of effective search strategy increased along with the time in all groups except for the chronic stress group. The rate of effective search strategy of the chronic stress group did not changed significantly during the 5 days. The number of pyramidal cell of the lidocaine treatment group was 61 +/- 3, significantly higher than that of the chronic stress group (52 +/- 4, P < 0.01), but not significantly different from those of the 2 control group (both P > 0.05). The average value of optical density of Nissl bodies of the lidocaine treatment group was 112 +/- 14, significantly higher than that of the chronic stress group (86 +/- 12, P < 0.01), but not significantly different from those of the 2 control groups. CONCLUSION: Chronic stress causes learning and memory dysfunction and injury of the pyramidal cells in the CA3 region of hippocampus. Lidocaine significantly alleviates the effects of chronic stress.