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 study the effects of ketamine on cAMP-response element binding protein(CREB) and brain-derived neurophic factor(BDNF) in the prefrontal cortex of depressed rats.Methods Forty male two-month-old Wistar rats weighed 180-220 g were equally randomized into 4 groups.On the 1st day of experiment,the rats were forced to swim for 15 min for establishing a depression model.On the 2nd day,normal saline 1 ml(group C),ketamine 5 mg/kg(group K1),10 mg/kg(group K2) and 15 mg/kg(group K3) with the same volume of 1 ml were intraperitoneally administered,respectively.Thirty minutes after administration,a forced swimming test(FST) was performed for 5 minutes to record the immobility time of rats.Then the preforntal cortex was harvested for detecting the expressions of CREB and BDNF.Results Compared with group C,groups of K1,K2 and K3 had a shorter immobility time and higher expressions of CREB and BDNF in the prefrontal cortex of the depressed rats in a dose-dependent manner(P〈0.05).Conclusion The antidepressant effect of ketamine is related to the up-regulation of CREB and BDNF expressions in the prefrontal cortex of rats.