5-HT_(1A)和5-HT_(3)受体在七氟烷诱发老龄大鼠脑神经毒性中的作用

Role of 5-HT_(1A) and 5-HT_(3) receptors in sevoflurane-induced cerebral neurotoxicity in aged rats

目的:5-羟色胺受体(5-HT_(1A)和5-HT_(3)受体)在七氟烷诱发老龄大鼠脑神经毒性中的作用。方法:清洁级健康雄性SD大鼠24只,18~20月龄,体重600~750 g,采用随机数字表法分为3组(n=8):分别吸入50%O_(2)(C组)、1.5%七氟烷+50%O_(2)(LS组)及3%七氟烷+50%O_(2)(HS组),持续2 h。于吸入七氟烷前1 d及结束后1 d时行旷场实验,记录中央格停留时间、跨格次数和站立次数;于吸入七氟烷前6 d时及结束后第1天行水迷宫实验,记录逃避潜伏期、游泳总距离和穿越平台次数。行为学实验结束即刻取海马组织,采用RT-PCR法和免疫组化法检测5-HT_(1A)和5-HT_(3)受体的mRNA表达水平及阳性细胞数。结果:与C组比较,HS组中央格停留时间延长,跨格次数及站立次数减少,逃避潜伏期延长,游泳总距离增加,穿越平台次数减少,5-HT_(1A)和5-HT_(3)受体的mRNA表达下调,阳性细胞数减少(P<0.05)。结论:七氟烷诱发老龄大鼠脑神经毒性的机制可能与下调5-HT_(1A)和5-HT_(3)受体活性有关。

Objective To preliminarily investigate the relationship between the mechanism of sevoflurane-induced cerebral neurotoxicity and receptors of 5-HT_(1A) and 5-HT_(3) in aged rats.Methods Twenty-four clean-grade healthy male Sprague-Dawley rats,aged 18-20 months,weighing 600-750 g,were divided into 3 groups(n=8 each)using a random number table method:group C,group LS and group HS.In group C,group LS and group HS,50%O_(2),1.5%sevoflurane plus 50%O_(2) and 3%sevoflurane plus 50%O_(2) were inhaled for 2 h,respectively.Open field test was performed at 1 day before inhalation of sevoflurane and at 1 day after the end of inhalation,the time spent in the central square,the number of crossing the grid and the number of standing on the back legs were recorded.The Morris water maze test was performed at 6 days before inhalation of sevoflurane and at 1 day after the end of inhalation,the escape latency,the total swimming distance and the number of crossing the platform were recorded.Immediately after the end of behavioral testing,the hippocampal tissues were obtained for determination of 5-HT_(1A) and 5-HT_(3) receptors mRNA expression and the number of positive cells(using real-time reverse transcription-polymerase chain reaction assay and immunohistochemical method).Results Compared with group C,the time spent in the central square was significantly prolonged,the number of crossing the grid and the number of standing on the back legs were decreased,the escape latency was prolonged,the total swimming distance was increased,the number of crossing platform was decreased,the mRNA expression of 5-HT_(1A) and 5-HT_(3) was down-regulated,and the number of positive cells was decreased in HS group(P<0.05).Conclusion The mechanism of cerebral neurotoxicity induced by sevoflurane may be related to the down-regulation of the activities of 5-HT_(1A) and 5-HT_(3) receptors in aged rats.