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四逆散對抑郁癥大鼠的治療效果及機制探究
方足兵1, 余雪丹1, 胡紅濤2, 董漢寧1
1.武漢市漢口醫院心理康復科, 武漢 430012;2.深圳康寧醫院心理康復科, 深圳 518020
摘要:
[目的] 探究四逆散對抑郁大鼠行為、中樞神經遞質及ERK1/2-CREB-BDNF信號通路的影響。[方法] 實驗大鼠隨機分為正常組、模型組、陽性對照組、四逆散低劑量組、四逆散中劑量組、四逆散高劑量組,每組20只。給藥結束后,進行糖水消耗實驗、曠場實驗;Elisa試劑盒檢測大鼠海馬組織中多巴胺(DA)、去甲腎上腺素(NE)、5-羥色胺(5-HT);放免試劑盒檢測血清中神經肽Y(NPY)、P物質(SP)、生長抑素(SS)含量;Western blot檢測皮質中ERK1/2-CREB-BDNF信號通路關鍵蛋白表達情況。[結果] 與正常組相比,模型組大鼠糖水偏愛度和曠場運動評分顯著降低(P均<0.001),海馬組織中DA、NE、5-HT含量顯著下調(P<0.001),血清中NPY、SS顯著下調(P<0.001),SP顯著上調(P<0.001),皮質中ERK1/2、CREB蛋白磷酸化水平及BDNF蛋白表達顯著下調(P<0.001);與模型組相比,四逆散給藥組大鼠糖水偏愛度和曠場運動評分顯著上調(P<0.001),海馬組織中DA、NE、5-HT含量顯著上調(P<0.001),血清中NPY、SS顯著上調(P<0.001),SP顯著下調(P<0.001),皮質中ERK1/2、CREB蛋白磷酸化水平及BDNF蛋白表達顯著增加(P<0.01)。[結論] 四逆散可上調海馬中神經遞質含量;調節血清神經肽水平;促進ERK1/2-CREB-BDNF信號通路磷酸化激活,發揮改善大鼠抑郁樣行為的功能。
關鍵詞:  抑郁癥  四逆散  神經遞質  ERK1/2-CREB-BDNF信號通路
DOI:10.11656/j.issn.1673-9043.2023.02.14
分類號:R285.5
基金項目:武漢市衛生和計劃生育委員會科研項目(WX18D33)。
Study on the therapeutic effect and mechanism of Sini San on depression rats
FANG Zubing1, YU Xuedan1, HU Hongtao2, DONG Hanning1
1.Department of Psychological Rehabilitation, Wuhan Hankou Hospital, Wuhan 430012, China;2.Department of Psychological Rehabilitation, Shenzhen Kangning Hospital, Shenzhen 518020, China
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.
Key words:  Depression  Sini San  Neurotransmitter  ERK1/2-CREB-BDNF signal path
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