摘要
目的 探讨异丙酚对氯胺酮致老龄大鼠认知功能障碍的影响.方法 健康雄性SD老龄大鼠32只,月龄18～24月龄,体重380～470 g,随机分为4组（n=8）：对照组（C组）、异丙酚组（P组）、氯胺酮组（K组）和异丙酚＋氯胺酮组（PK组）.P组静脉输注异丙酚30 mg·kg^-1·h^-1,K组静脉输注氯胺酮40 mg·kg^-1·b^-1,PK组静脉输注异丙酚30 mg·kg^-1·h^-1＋氯胺酮40 mg·kg^-1·h^-1,C组给予等容量生理盐水,每天2 h,连续7 d.给药结束后测定大鼠认知功能,记录逃避潜伏期和穿越平台次数.认知功能测试完毕后,处死大鼠,取海马组织,检测CA1区神经元凋亡情况,计算神经元凋亡率;测定CA1区caspase-3的表达水平.结果 与C组比较,P组逃避潜伏期、穿越平台次数、海马CA1区神经元凋亡率和caspase-3表达差异无统计学意义（P＞0.05）,K组和PK组逃避潜伏期延长,穿越平台次数减少,海马CA1区神经元凋亡率升高,caspase-3表达上调（P＜0.05）;与K组比较,PK组逃避潜伏期缩短,穿越平台次数增加,海马CA1区神经元凋亡率降低,caspase-3表达下调（P＜0.05）.结论 异丙酚可减轻氯胺酮致老龄大鼠认知功能障碍,其机制可能与异丙酚可在一定程度上抑制氯胺酮所致caspase-3表达上调,从而抑制氯胺酮诱发的神经元凋亡有关.
Objective To investigate the effect of propofol on ketamine-induced cognitive dysfunction and neuronal apoptosis in hippocampus in aged rats. Methods Thirty-two male SD rats aged 18-24 months weighing 380-470 g were randomly divided into 4 groups （ n = 8 each） ：control group （group C）;propofol group （group P）;ketamine group （group K） and propofol ＋ ketamine group （group PK）. Propofol 30 mg·kg^-1·h^-1 or/and ketamine 40 mg· kg^-1·h^-1 were infused for 2 h once a day for 7 consecutive days. After the last day of drug administration cognitive function was assessed using Morris water maze （escape latency and the number of animals＇ swimming across the platform）. The animals were sncrificed after water naze test and their hippocampi were removed for determination of neuronal apoptosis （by TUNEL） and caspase-3 expression （by immuno-histochemistry） in hippocampal CA1 region. Results There was no significant difference in escape latency and the number of the animals,swimming across the platform, the neuronal apoptotic rate （the number of apoptotic neurons/the number of total neurons） and caspase-3 expression between group C and P. In group K and PK the escape latency was prolonged,the number of animals＇ swimming across the platform was decreased, neuronal apoptotic rate increased and the caspase-3 expression up-regulated as compared with group C. The ketamine-induced changes were significantly attenuated by coadministration of propofol in group PK. Conclusion Coadministration of propofol can ameliorate ketamine-induced cognitive dysfunction and hippocampal neuronal apoptosis.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2010年第9期1085-1087,共3页
Chinese Journal of Anesthesiology
