咪唑安定、异丙酚和氯胺酮对老年大鼠认知功能的影响

Effects of midazolam, ketamine and propofol on cognitive function in aged rats

目的探讨咪唑安定、异丙酚和氯胺酮对老年大鼠认知功能及海马N-甲基-D-天冬氨酸受体亚单位NR1、NR2B mRNA表达的影响。方法 32只老年Wistar大鼠随机分为4组,对照组(N组, n=9),咪唑安定组(M组,n=8),异丙酚组(P组,n=7),氯胺酮组(K组,n=8),M、P、K组分别以 30、60、80mg·kg-1·d-1的剂量腹腔注射咪唑安定、异丙酚、氯胺酮,连续3 d,N组给予生理盐水2 ml。于停药后1d行水迷宫测试,连续3 d,记录潜伏期(入水时至找到平台的时间)及游泳距离(入水时至找到平台的行程),连续测试3 d,末次迷宫测试结束后1h处死大鼠,用逆转录-聚合酶链反应方法测定海马NR1、NR2B mRNA表达。结果与水迷宫测试1d比较,N、K、P组水迷宫测试3 d潜伏期缩短及游泳距离缩短,与N组比较,K组水迷宫测试1 d潜伏期延长,水迷宫测试2 d游泳距离延长,M组 NR1 mRNA表达增加,P、K组NR2B mRNA表达降低(P<0．05或0．01)。结论咪唑安定和异丙酚对老年大鼠认知功能没有明显影响;氯胺酮对老年大鼠认知功能有短暂的抑制作用;海马NR1、NR2B mRNA表达与认知功能无关。

Objective To investigate the effects of midazolam, ketamine and propofol on spatial cognitive function and the mRNA expression of N-methyl-D-aspartate （NMDA） receptor subunits NR1 and NR2B in the hippocampus of aged rats. Methods Thirty-two Wistar rats of both sexes aged 18 months were randomly divided into 4 groups ： Ⅰ control group （ n = 9） ; Ⅱ midazolam group （M, n = 8）;Ⅲ propofol group （P, n = 7） and Ⅳ ketamine group （K, n = 8）. The animals received intraperitoneal （IP） midazolam 30 mg·kg^-1 or propofol 60 mg · kg^- 1 or ketamine 80 mg·kg^-1 once a day for 3 days whereas the animals in control group received IP normal saline 2 ml instead. One day after the last drug administration the animals underwent Morris water maze test 4 times a day for 3 consecutive days. The animals were killed at lh after last test and the brains were immediately removed for determination of NR1 and NR2B mRNA expression in the hippocampus using RT-PCR. Results The latency period and swimming distance were significantly shorter on the 3rd day of water maze test than on the 1st day in control group and group K, P. The latency period on the 1 st day was significantly longer in group K than in control group. The NR1 mRNA expression in group M was significantly higher while the NR2B mRNA expression in group K and P was significantly lower than that in control group （ P 〈 0.05 or 0.01 ）. Conclusion Midazolam （30 mg·kg^-1·day^-1 ） or propofol （60 mg· kg^-1 · day^-1 ） does not have any significant effect on spatial cognitive function of the aged rats. Ketamine （80 mg· kg^- 1 · day^-1 ） has short-term inhibitory effect on cognitive function. The NMDA receptor subunits NR1 and NR2B in hippocampus are not involved in the cognitive function.