摘要目的 评价七氟醚对小鼠记忆提取的影响及海马突触后密度蛋白95(PSlD95)和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体在其中的作用.方法 清洁级健康昆明小鼠64只,2～3月龄,雌雄不拘,体重30～ 35 g按随机Ⅸ组设计,将其分为2组(n=32):对照组和七氟醚组 采用避暗实验评价记忆提取能力 建立避暗记忆后,对照组吸入40％O22h,七氟醚组吸入3.3％七氟醚及40％O22 h 于吸入七氟醚或吸氧结束后12、24、48和72 h(T1-T4)时进行避暗记忆测试,记录测试期成绩和遗忘发生情况 各时点行为学测试后处死小鼠,取脑组织,行HE染色,光镜下观察海马CA1区病理学结果;分别采用免疫组化法和Western blot法测定海马PSD95与AMPA受体的表达水平.结果 与对照组比较,七氟醚组T1和T2时步入潜伏期和错误次数的测试期成绩降低,海马PSD95和AMPA受体表达下调,遗忘发生率升高(P＜0.05).与基础成绩比较,对照组步入潜伏期和错误次数的测试期成绩差异无统计学意义(P＞0.05),七氟醚组T1和T2时步入潜伏期和错误次数的测试期成绩降低(P＜0.05). 七氟醚组未见明显的锥体细胞凋亡.结论 七氟醚可一过性抑制小鼠记忆提取能力,机制与抑制海马PSD95及AMPA受体表达有关.

abstractsObjective To evaluate the effect of sevoflurane on memory retrieval in mice and the role of hippocampal PSD95 and amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor.Methods Sixty-four healthy pathogen-free Kuming mice of both sexes,aged 2-3 months,weighing 30-35 g,were divided into control group (n =32) and sevoflurane group (n =32) in a stratified randomized block design.The ability of memory retrieval was evaluated using dark avoidance test.After setting up the memory of dark avoidance,the mice inhaled 40％ oxygen for 2 h in control group and 3.3％ sevofluane in 40％ oxygen for 2 h in sevoflurane group.Dark avoidance test was performed at 12,24,48 and 72 h after the end of oxygen or sevoflurane inhalation (T1-4),and the test results and development of amnesia were recorded.The animals were sacrificed after behavior test at each time point,and brains were removed and cut into sections which were stained with haematoxylin and eosin for examination of the pathological changes of hippocampal CA1 area (under a light microscope) and for determination of the expression of PSD95 and AMPA receptors in hippocampi (using immunohistochemistry and Western blot).Results Compared with control group,the step-in latency and test results of error times were significantly decreased,the expression of PSD95 and AMPA receptors in hippocampus was down-regulated,and the incidence of amnesia was increased at T1 and T2 in sevoflurane group (P＜0.05).Compared with the basic results,no significant change was found in the step-in latency or test results of error times in control group (P＞0.05),and the step-in latency and test results of error times were significantly decreased at T1 and T2 in sevoflurane group (P＜0.05).Apoptosis in pyramidal cells was not found in sevoflurane group.Conclusion Sevoflurane can inhibit the ability of memory retrieval transiently in mice,and the mechanism is related to inhibiting the expression of hippocampal PSD95 and AMPA receptors.