不同剂量氯胺酮对抑郁大鼠海马脑源性神经营养因子和酪氨酸受体激酶B的影响

Effects of different doses of ketamine on brain-derived neurotrophic factor and tyrosine receptor kinase B in hippocampus in mentally depressed rats

目的探讨不同剂量氯胺酮对抑郁大鼠海马脑源性神经营养因子（BDNF）及酪氨酸受体激酶B（TrkB）的影响。方法雄性Wistar大鼠50只，体重180～220g，月龄2月，采用随机数字表法，将大鼠随机分为5组（n=10）：对照组（C组）和不同剂量氯胺酮组（K1-4组）。采用强迫游泳实验建立抑郁大鼠模型。药物干预前1d大鼠强迫游泳15min，药物干预当日，分别腹腔注射生理盐水1．0ml（C组）、氯胺酮2．5mg／kg（K1组）、5．0mg／kg（K2组）、10．0mg/kg（K3组）、20．0mg／kg（K4组）。给药后30min将大鼠再次行强迫游泳实验，观察并记录不动时间。行为学测试后，取海马组织测定BDNF及TrkB的含量。结果与C组比较，K1-4组不动时间缩短，K组和I（4组海马BDNF、TrkB含量升高（P〈0．05）；K1-4组随氯胺酮浓度升高，不动时间缩短（P〈0．05），与K1组或K2组比较，K1组和K4组海马BDNF、TrkB含量升高（P〈0．05）。结论氯胺酮可呈剂量依赖性地发挥抗抑郁作用，可能与增加大鼠海马BDNF和TrkB含量有关。

Objective To investigate the effects of different doses of ketamine on brain-derived neurotrophic factor （BDNF） and tyrosine receptor kinase B （TrkB） in the hippocampus in mentally depressed rats. Methods Fifty male Wistar rats weighing 180-220 g were randomly divided into 5 groups （ n = 10 each） ： group control （group C） and groups K1-4 ketamine 2.5, 5.0, 10.0 and 20.0 mg/kg. On the 1st day the animals were forced to swim for 15 min. On the 2nd day ketamine 2.5, 5.0, 10.0 and 20.0 mg/kg were given intraperitoneally in groups K1-4 respectively at 30 min after administration. The immobility time of the rats during the forced swimming test was recorded. The animals were then decapitated. The hippocampus was harvested for determination of BDNF and TrkB levels. Results Ketamine significantly decreased the immobility time during forced swimming test in a dose-dependent manner. The BDNF and TrkB levels in the hippocampus were significantly increased in K3 and K4 groups as compared with group C, and K1 and K2 groups. Conclusion The increased levels of BDNF and TrkB in the hippocampus are involved in the dose-dependent antidepressant effect of ketamine.