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目的观察氯胺酮对抑郁大鼠大脑前额皮层环磷酸腺苷反应元件结合蛋白(CREB)及脑源性神经营养因子(BDNF)的影响。方法雄性2月龄Wistar大鼠40只,体重180~220 g,随机均分为四组。实验第1天,大鼠行强迫游泳15 min,建立抑郁模型;第2天,四组分别腹腔注射容积为1 ml的生理盐水(C组)、氯胺酮5 mg/kg(K1组)、10 mg/kg(K2组)和15 mg/kg(K3组)。给药30 min后再次行强迫游泳实验5 min,记录其不动时间。随后取前额皮层组织测定CREB及BDNF表达。结果与C组相比,K1、K2和K3组呈剂量依赖性地减少抑郁大鼠强迫游泳不动时间,增加前额皮层CREB和BDNF表达(P<0.05)。结论氯胺酮对大鼠的抗抑郁作用可能与前额皮层CREB及BDNF上调有关。
Objective To investigate the effects of ketamine on cAMP responsive element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex of rats with depression. Methods Forty male Wistar rats of 2 months old weighing 180-220 g were randomly divided into four groups. On the first day of the experiment, rats were forced to swim for 15 min to establish a model of depression. On the second day, four groups were intraperitoneally injected with 1 ml normal saline (group C), ketamine 5 mg / kg (K1 group) / kg (K2 group) and 15 mg / kg (K3 group). After 30 min of administration, forced swimming test was performed again for 5 min, and the immobility time was recorded. Subsequently, the expression of CREB and BDNF was measured in the prefrontal cortex. Results Compared with group C, K1, K2 and K3 groups decreased forced forced swimming time and increased expression of CREB and BDNF in the prefrontal cortex in a dose - dependent manner (P <0.05). Conclusion The antidepressant effects of ketamine in rats may be related to the upregulation of CREB and BDNF in the prefrontal cortex.