氯胺酮通过改变Fos和Bcl-2表达减轻缺氧对大鼠海马群峰电位的抑制

Ketamine Alleviates Hypoxia-induced Inhibition of Population Spikes of Rat Hippocampus by Changing Expression of Fos and Bcl-2

目的通过观察氯胺酮处理对缺氧引起的大鼠海马诱发群峰电位、神经元Fos、Bcl-2表达的影响,探讨氯胺酮对神经元缺氧性损伤保护作用机制。方法脑片以及培养细胞随机分为3组:对照组(不进行缺氧处理)、缺氧组和氯胺酮组(缺氧前于培养液中加入氯胺酮,终浓度为20μmol/L,其它处理同缺氧组)。脑片记录:成年雄性Wistar大鼠麻醉后取海马切片,进行CA3区Schaffer侧支刺激,记录CA1区椎体细胞诱发电位。新生大鼠海马神经元培养7~11d,分组处理后进行免疫组化染色,计算Fos、Bcl-2阳性细胞率。结果氯胺酮预处理后,海马脑片群峰电位开始减小和完全消失的时间延迟;培养海马神经细胞Fos表达阳性率、平均吸光度值与缺氧组比较明显减少(均P<0.05);海马神经细胞Bcl-2表达阳性率、平均吸光度值与缺氧组比较明显增加(均P<0.05)。结论氯胺酮预处理对大鼠海马群峰电位的保护作用可能是通过减少缺氧后Fos表达、增加Bcl-2表达来实现的。

Objective To discuss the protective role of ketamine in hypoxia-induced damage of neurons by examining the effect of ketamine on population spikes in hypoxia and the expression of Fos and Bcl-2 in rat hippocampus.Methods The hippocampal slices and cultured hippocampal neurons were randomly divided into three groups：control group,in which no hypoxic treatment was given;hypoxia group and ketamine group.In the ketamine group,the slices and the neurons were treated with 20μmol/L ketamine before inducement of hypoxia.The hippocampal slices were obtained from adult male Wistar rats after anesthetization.The Schaffer collaterals in CA3 area were stimulated and the evoked potentials were recorded in CA1 area.The hippocampal neurons of new-born rats were cultured for 7-11 days and staining was performed in neurons in different groups by using anti-goat Fos and anti-rabbit Bcl-2 serum,and the absorbance was detected.Results The decrease in the population spikes and the total disappearance of the spikes were delayed in hippocampal slices pretreated with ketamine.The positive expression rate of Fos and the average absorbance value were significantly lower in ketamine group than in anoxic group（P0.05）,whereas the positive expression rate of Bcl-2 expression and the average absorbance value were significantly higher in ketamine group than in hypoxia group（P0.05）.Conclusion Pretreatment with ketamine alleviates hypoxia-induced inhibition of population spikes by decreasing Fos and increasing Bcl-2 expression.