四逆散对抑郁症大鼠的治疗效果及机制探究

Study on the therapeutic effect and mechanism of Sini San on depression rats

关键词:  抑郁症  四逆散  神经递质  ERK1/2-CREB-BDNF信号通路

Key words:  Depression  Sini San  Neurotransmitter  ERK1/2-CREB-BDNF signal path

摘要:

[目的] 探究四逆散对抑郁大鼠行为、中枢神经递质及ERK1/2-CREB-BDNF信号通路的影响。[方法] 实验大鼠随机分为正常组、模型组、阳性对照组、四逆散低剂量组、四逆散中剂量组、四逆散高剂量组，每组20只。给药结束后，进行糖水消耗实验、旷场实验；Elisa试剂盒检测大鼠海马组织中多巴胺（DA）、去甲肾上腺素（NE）、5-羟色胺（5-HT）；放免试剂盒检测血清中神经肽Y（NPY）、P物质（SP）、生长抑素（SS）含量；Western blot检测皮质中ERK1/2-CREB-BDNF信号通路关键蛋白表达情况。[结果] 与正常组相比，模型组大鼠糖水偏爱度和旷场运动评分显著降低（P均<0.001），海马组织中DA、NE、5-HT含量显著下调（P<0.001），血清中NPY、SS显著下调（P<0.001），SP显著上调（P<0.001），皮质中ERK1/2、CREB蛋白磷酸化水平及BDNF蛋白表达显著下调（P<0.001）；与模型组相比，四逆散给药组大鼠糖水偏爱度和旷场运动评分显著上调（P<0.001），海马组织中DA、NE、5-HT含量显著上调（P<0.001），血清中NPY、SS显著上调（P<0.001），SP显著下调（P<0.001），皮质中ERK1/2、CREB蛋白磷酸化水平及BDNF蛋白表达显著增加（P<0.01）。[结论] 四逆散可上调海马中神经递质含量；调节血清神经肽水平；促进ERK1/2-CREB-BDNF信号通路磷酸化激活，发挥改善大鼠抑郁样行为的功能。

Abstract:

[Objective] To investigate the effects of Sini San on behavior, central neurotransmitter and ERK1/2 creb-BDNF signaling pathway in depressed rats.[Methods] The experimental rats were randomly divided into normal group, model group, positive control group, Sini San low-dose group, Sini San medium-dose group and Sini San high-dose group, with 20 rats in each group. After administration, sugar water consumption experiment and open field experiment were carried out. Elisa kit was used to detect dopamine(DA), norepinephrine(NE) and 5-hydroxytryptamine(5-HT) in hippocampus of rats. The contents of neuropeptide Y(NPY), substance P(SP) and somatostatin(SS) in serum were detected by radioimmunoassay kit. Western blot was used to detect the expression of key proteins in erK1/2-CREb-BDNF signaling pathway in the cortex.[Results] Compared with normal group, sugar water preference and open field movement score in model group were significantly decreased(P<0.001);the contents of DA, NE and 5-HT in hippocampus were significantly down-regulated(P<0.001);NPY and SS in serum were significantly down-regulated (P<0.001);SP was significantly up-regulated(P<0.001). The phosphorylation levels of ERK1/2 and CREB proteins and the expression of BDNF protein were significantly down-regulated in cortex(P<0.001). Compared with model group, sugar water preference and open field motion score in Sini San administration group were significantly up-regulated(P<0.001);DA, NE and 5-HT contents in hippocampus were significantly up-regulated(All P <0.001), NPY and SS in serum were significantly up-regulated (P<0.001), SP was significantly down-regulated(All P<0.001). The phosphorylation levels of ERK1/2 and CREB protein and the expression of BDNF protein in cortex were significantly increased (P<0.01).[Conclusion] Sini San can up-regulate the neurotransmitter content in hippocampus, regulate the level of serum neuropeptide, promote phosphorylation and activation of ERK1/2-CREB-BDNF signaling pathway, and play the function of improving depression-like behavior in rats.