摘要
目的:探讨长期亚麻醉剂量氯胺酮对青少年食蟹猴自发活动、前额叶和海马脑源性神经营养因子(Brainderived neurotrophic factor,BDNF)和环磷腺苷效应元件结合蛋白(cAMP response element binding protein,CREB)的影响。方法:36只雄性食蟹猴(3.7-4.8岁)随机分为对照组,1个月、3个月和6个月氯胺酮组,氯胺酮组每日静脉注射氯胺酮(1mg/kg),对照组注射同体积生理盐水。比较给药前,给药1个月,3个月,6个月后动物的自发活动、前额叶和海马神经元形态及BDNF和CREB水平。结果:1个月氯胺酮组移动显著多于对照组;3个月组行走显著多于对照组;6个月组移动和攀爬显著低于对照组。氯胺酮导致前额叶和海马神经元数量减少,细胞排列紊乱,细胞间隙疏松、增大,部分细胞核固缩。氯胺酮组前额叶BDNF表达水平显著低于对照组;CREB表达水平在3个月组和6个月组显著低于对照组和1个月组。海马CREB表达水平在6个月组显著低于对照组、1个月组和3个月组。结论:长期亚麻醉剂量氯胺酮导致青少年食蟹猴自发活动由兴奋到抑制、前额叶和海马神经元损伤、BDNF和CREB表达降低。
Objective: To examine the effects of long-term subanesthetic ketamine on spontaneous activity, brain-derived neurotrophic factor(BDNF) and cAMP response element binding protein(CREB) expression in the prefrontal cortex(PFC) and hippocampus(HIP) in adolescent monkeys. Methods: 36 male cynomolgus monkeys(3.7-4.8 years old) were divided into control group and 3 ketamine groups. Monkeys of ketamine groups were intravenously administered ketamine(1 mg/kg) once daily for 1, 3 and 6 months while the monkeys in control group were intravenously administered saline. Results: 1-month ketamine group had more movement than control group;3-month ketamine group had more walking than control group while 6-month ketamine group had less moving and climbing than control group. Ketamine reduced the number of neurons, disordered cell arrangement, loosened and enlarged intercellular space, and cell nuclei pyknosis in the PFC and HIP. In the PFC, the BDNF expression of ketamine groups was lower than that of the control, the CREB expression of 3-month and 6-month groups was lower than that of control and 1-month group. In the HIP, the CREB expression of 6-month group was lower than that of control, 1-month and 3-month groups. Conclusion: Long-term subanesthetic dose of ketamine results in spontaneous activity from excitation to inhibition, neuronal damage and lower levels of BDNF and CREB in the PFC and HIP of juvenile cynomolgus monkeys.
作者
孙阮正奇
王力
尹世平
刘德祥
YEW Tai-wai David
潘芳
SUN Ruan-zhengqi;WANG Li;YIN Shi-ping;LIU De-xiang;PAN Fang(Queen Mary University, Nanchang University, Nanchang 330031, China;Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan 250012, China;Department of Medical Psychology and Ethnic, School of Basic Medical Sciences, Shandong University, Jinan 250012, China;School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong 999077, China)
出处
《中国临床心理学杂志》
CSSCI
CSCD
北大核心
2019年第5期859-862,893,共5页
Chinese Journal of Clinical Psychology
基金
香港特别行政区禁毒署(080048)
国家自然基金(31371036)
