七氟醚对老年大鼠认知功能及大脑额叶GABAR1和NMDAR2B表达的影响

Effect of sevoflurane on cognitive function and expression of GABA receptor 1 and NMDA receptor 2B in frontal cortex in aged rats

目的观察七氟醚对老年大鼠学习记忆能力的影响以及与脑右侧前额叶γ-氨基丁酸受体1(GABAR1)和N-甲基-D-天冬氨酸受体2B(NMDAR2B)表达变化的关系。方法雄性SD老年大鼠模型50只,随机分为对照组(C组,n=10)和实验组(T组,n=40)。C组吸入室温空气,实验组按3%浓度吸入七氟醚持续时间不同分为T1组(吸入2h)和T2组(吸入4h),C组全部,T1和T2组各取10只大鼠分别在麻醉后1天和7天进行Morris水迷宫实验,检测老年大鼠的空间学习记忆能力,采用定量RT-PCR技术和免疫荧光技术分别检测右侧前额叶GABAR1和NMDAR2B的mRNA转录水平和蛋白含量。结果与C组比较,吸入七氟醚第1天T1和T2组逃避潜伏期明显延长,空间探索穿越次数明显减少,GABAR1的mRNA表达量和蛋白含量明显上调,NMDAR2B的mRNA表达量和蛋白含量明显下调(P<0.05)。与C组比较,吸入七氟醚后第7天T2组逃避潜伏期明显延长,空间探索穿越次数明显减少,T2组GABAR1 mRNA表达量和蛋白含量明显上调,NMDAR2B的mRNA表达量和蛋白含量明显下调,且T2组GABAR1蛋白含量明显高于,NMDAR2B蛋白含量明显低于T1组(P<0.05)结论长时持续吸入七氟醚相较于短时持续吸入对空间学习记忆能力下降的影响较大,且持续影响时间较长。这种影响与脑额叶中GABAR1和NMDAR2B的表达变化相关。

Ojective To observe the change of learning and memory and the expression change of GABAR1 and N-methyl-D-aspartate receptor 2B （NMDAR2B） in right frontal lobe of the brain of the aged rats after the inhalation of sevoflurane. Methods Fifty male SD rats were randomly divided into control group （group C, n=10） and experimental group （group T, n=40）. The control group received air at room tempreture. Experimental groups were divided into two groups： group T1 （2 h） and group T2 （4 h） according to the time of inhalation of sevoflurane at 3% concentration. Every group was equally divided into two groups and Morris water maze was performed on day 1 and day 7 after sevoflurane inhalation. Then the right frontal lobe was gathered and the mRNA transcription and protein expression of GABAR1 and NMDAR2B were detected by Quantitative Real-time PCR and immunofluorescence technique. Results Compared with group C, the escape latency was prolonged in groups T1 and T2 after 1 day of inhalation of sevoflurane （P〈0.05）, and the times of space exploration reduced （P〈0.05）. mRNA transcriptional and protein content of GABAR1 were significantly upregulated in frontal lobes of groups T1 and T2, mRNA transcriptional and protein content of NMDAR2B were significantly down-regulated （P〈0.05）. After inhalation of sevoflurane for 7 days, the protein expression of NMDAR2B in the frontal lobe of group T1 was lower than that of group C （P〈0.05）. In group T2, the escape latency was prolonged （P〈0.05）, the number of space exploration traversals was decreased （P〈0.05）, the expression of GABAR1 protein in frontal lobe was up-regulated （P〈0.05）, and the expression of NMDAR2B protein was down-regulated （P〈0.05）, and the amplitude was higher than that in group T1 （P〈0.05）. Conclusion Continuous inhalation of sevoflurane can reduce the spatial memory ability of aged rats, and the effect of prolonged inhalation is greater and longer. This effect is related to the expression of neurotransmitter receptors such as GABAR1 and NMDAR2B in the frontal lobe.