咯利普兰对小鼠抑郁模型信号转导通路的影响

Effect of rolipram on the signal transduction pathway in depressed mice

【目的】阐明咯利普兰抗抑郁作用的信号转导途径。【方法】48只小鼠按照随机原则分为空白对照组、重复应激抑郁梗重组、咯利姜兰低剂量组(3mg/kg)、咯利普兰剂量级(6mg/kg),每组12只。采用强迫游泳,禁食,禁水,冰水游泳等方法,建立小鼠重复应激抑郁模型,造模同时给予咯利普兰(3mg/kg、6mg/kg),10d后断头取海马组织进行检测。采用用放射免疫学检测小鼠海马内cAMP含量及PKA活力,采用蛋白印迹学检测海马P-CREB及BDNF水平。【结果】咯利普兰可显著缩短强迫游泳试验中小鼠的不动时间,对照组为(176.24±35.42)s,咯利普兰组分别为(105.64±41.51)s、(118.79±39.23)s,表明在强迫游泳试验中,咯利普兰具有抗抑郁作用。信号转导途径表达为:咯利普兰可显著提高应激小鼠海马内cAMP含量,空白组(72.13±3.58)pmol/mg、模型组(47.85±4.76)pmol/mg、咯利普兰(3mg/kg)(62.91±4.27)pmol/mgprotein、咯利普兰(6mg/kg)(64.13±3.93)pmol/mg,增加海马内PKA的活力,增加磷酸化CREB和BDNF的表达,各组间有显著性差异(P<0.05)。【结论】cAMP-PKA-CREB-BDNF是咯利普兰发挥抗抑郁作用信号转导途径之一。

[ Objective] To observer the effect of rolipram on the signal transduction pathway in depressed mice. To observer the effect of rolipram on the signal transduction pathway in depressed mice. [Methods] A total of 48 mice were divided into 4 groups at random, 12 in eadngroup. Animal models of repeated sfimulatation were estabhshed in rats by behaviors tests, such as forced swimming test, absolute, forbidden water , swim in ice water and so on. Radioimmunity study were employed to determine the content of cAMP and the activity of PKA, The expression of phospuorylated CREB and BDNF were dectected by western blot analysis. [ Results] Rolipram could decrease the rest time in the forced swim test significantly in the forced swimming test. It could improve the content of cAMP and the activity of PKA significantly when compared with depressed animals, It could also increase the expression of phospuorylated CREB and BDNF when compared with model mice. [ Conclusions] cAMP-PKA-CREB-BDNF pathway is one of the rolipam＇s signal transduction pathway in its antidepressant role.