西酞普兰对脑卒中后抑郁大鼠海马齿状回5-羟色胺_(1A)受体表达的影响

Expression of protein and mRNA of 5-HT_(1A) receptor in the dentate gyrus of post-stroke depression

目的观察西酞普兰对拟脑卒中后抑郁(post-stroke depression,PSD)大鼠海马齿状回5-羟色胺1A(5-HT1A)受体表达的影响,探讨其治疗PSD可能的药理机制。方法将雄性SD大鼠分为3组:正常对照组、拟PSD组和西酞普兰干预组。左侧大脑中动脉阻塞(MCAO)联合慢性不可预见温和应激刺激(CMS)及孤养法建立拟PSD动物模型,同时予西酞普兰(10mg.kg-1.day-1)干预4周,荧光实时定量PCR和Western印迹方法检测并比较CMS开始后第19、28天各组大鼠海马齿状回5-HT1A受体的基因(mRNA表达水平)和蛋白表达水平。结果CMS开始后第19天,西酞普兰组5-HT1A受体的基因和蛋白表达均高于拟PSD组[(0.131±0.008)vs(0.012±0.001)和(0.95±0.06)vs(0.40±0.03),P均小于0.001]。第28天,西酞普兰组5-HT1A受体的基因和蛋白表达均高于拟PSD组[(0.224±0.012)vs(0.013±0.001)和(0.52±0.06)vs(0.08±0.02),P均小于0.001]。结论西酞普兰促进拟PSD大鼠海马齿状回5-HT1A受体的基因和蛋白表达,从而可促进海马神经重塑,这可能为西酞普兰治疗PSD的分子机制之一。

Objective To explore the effects of citalopram on the expression of 5-HT1A receptor in the dentate gyrus in a rat model of post-stroke depression （PSD）, and its pharmacological mechanisms in the treatment of PSD in rats. Methods Male Sprague-Dawley rats were divided into 3 groups： the control group, PSD group and citalopram group. Animals were subjected to consistent focal cerebral infarcts through left middle cerebral artery occlusion （MCAO）, followed by 18-day exposure to chronic mild stress （CMS） and single housing in order to induce putative PSD model. Citalopram （10 mg ·kg^-1·day^-1 was injected intraperitoneally for 4 weeks from the begining of CMS procedure. The expression of mRNA and protein of the 5-HT1A receptor was assayed by Western Blotting and Real-Time Reverse-Transcription PCR on the 19th and 28th day after the begining of the CMS procedure respectively. Results On the 19th day after the begining of the CMS procedure, citalopram increased the expression of 5-HT1A receptor mRNA （P 〈 0. 001 ） and protein （ P 〈 0. 001 ） compared with the PSD rats. On the 28th day, citalopram increased the expression of 5-HT1A receptor mRNA （P 〈 0. 001 ） and protein （P 〈 0. 001 ） compared with the PSD rats. Conclusions Citalopram increased the expression of 5-HT1A receptor mRNA and protein in the dentate gyrus in a rat model of PSD, suggesting that this might be one of the molecular mechanism of the effects of antidepressants on the hippocampal neurogenesis and the effectiveness in the treatment of PSD.