基于NO-cGMP信号转导通路交泰丸对慢性温和不可预知性应激抑郁大鼠的抗抑郁作用研究
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摘要
目的基于一氧化氮-环磷酸鸟苷酸(NO-cGMP)信号转导通路探讨交泰丸对慢性温和不可预知性应激(CUMS)抑郁模型大鼠的抗抑郁作用。方法采用CUMS进行大鼠抑郁模型造模,实验第21天各给药组连续ig治疗药物14 d。采用ELISA法检测大鼠海马组织及血浆中NO和cGMP水平;RT-PCR法检测大鼠海马组织中一氧化氮合酶(包括iNOS、nNOS)及NMDA受体亚单位NR1、NR2A和NR2B基因mRNA表达。结果与对照组比较,模型组大鼠海马组织及血浆中NO、cGMP水平明显升高;大鼠海马组织中iNOS mRNA、nNOS mRNA、NR1 mRNA、NR2A mRNA、NR2B mRNA表达显著升高。与模型组相比,交泰丸高、中、低剂量(3.00、1.50、0.75 g/kg)及阳性药盐酸氟西汀均可逆转以上指标的改变。结论交泰丸可通过调节NO-cGMP信号转导通路达到抗抑郁作用。
Objective To investigate the effect of Jiaotai Pills on antidepressants in chronic mildly unpredictable stress(CUMS) depression model rats based on nitric oxide-cyclic guanosine monophosphate(NO-cGMP) signal transduction pathway. Methods The depression model of rats was induced by CUMS. On day 21 of the experiment, the rats in each group were treated with continuous ig administration for 14 d. The concentrations of NO and cGMP in hippocampus and plasma of rats were detected by Elisa method. The m RNA expression of NO synthase(including iNOS and nNOS) and NMDA receptor subunits NR1, NR2A, and NR2B in rat hippocampus was detected by RT-PCR. Results Compared with the control group, the levels of NO and cGMP in the hippocampus and plasma in the model group were significantly increased. The expressions of iNOS mRNA, nNOS mRNA, NR1 mRNA, NR2A mRNA, and NR2B mRNA in the hippocampus were significantly increased in the model group. Compared with the model group, Jiaotai Pills high, medium, and low dose and positive drug administration reversed the above changes. Conclusion Jiaotai Pills have the antidepressant effect on depression rats with CUMS by regulating NO-cGMP signal transduction pathway.
Objective To investigate the effect of Jiaotai Pills on antidepressants in chronic mildly unpredictable stress(CUMS) depression model rats based on nitric oxide-cyclic guanosine monophosphate(NO-cGMP) signal transduction pathway. Methods The depression model of rats was induced by CUMS. On day 21 of the experiment, the rats in each group were treated with continuous ig administration for 14 d. The concentrations of NO and cGMP in hippocampus and plasma of rats were detected by Elisa method. The m RNA expression of NO synthase(including iNOS and nNOS) and NMDA receptor subunits NR1, NR2A, and NR2B in rat hippocampus was detected by RT-PCR. Results Compared with the control group, the levels of NO and cGMP in the hippocampus and plasma in the model group were significantly increased. The expressions of iNOS mRNA, nNOS mRNA, NR1 mRNA, NR2A mRNA, and NR2B mRNA in the hippocampus were significantly increased in the model group. Compared with the model group, Jiaotai Pills high, medium, and low dose and positive drug administration reversed the above changes. Conclusion Jiaotai Pills have the antidepressant effect on depression rats with CUMS by regulating NO-cGMP signal transduction pathway.
引文
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[3]龚梦鹃,岳贺,周祥羽,等.交泰丸干预对氯苯丙氨酸致大鼠失眠的作用机制研究[J].世界中西医结合杂志,2017,12(9):1230-1234.
[4]王宁,常顺.交泰丸加味治疗失眠89例临床观察[J].河北中医,2004,26(6):442-442.
[5]Kou J,Wu Y,Wang Q,et al.Studies on the sedative and hypnotic activities of Jiaotai Wan prepared by raw or wine-processed Coptidis Rhizoma[J].Pharmacol Clin Chin Mater Med,2007,23(5):15-17.
[6]瞿彬,张蓉,杨云霜,等.交泰丸加减方治疗失眠症50例[J].陕西中医,2016,37(12):1632-1634.
[7]于春泉,王怡,高杉,等.交泰丸不同配比抗抑郁作用的实验研究[J].中国实验方剂学杂志,2012,18(6):225-228.
[8]张潇,高耀,向欢,等.基于网络药理学的交泰丸治疗抑郁症作用机制研究[J].中草药,2017,48(8):1584-1590.
[9]吴琨,时京珍,曲莉莎,等.交泰丸抗抑郁作用的药理实验研究[J].贵阳中医学院学报,2009,31(5):29-31.
[10]杨帅,潘晔,宋彦奇,等.交泰丸对抑郁大鼠行为学及脑内单胺类神经递质的影响[J].中草药,2016,47(23):4218-4223.
[11]梁如,殷佳,潘晔,等.交泰丸对慢性温和不可预知性应激抑郁模型大鼠炎性细胞因子的影响[J].中草药,2018,49(5):1100-1105.
[12]于泽胜,路腾飞,周好波,等.柴胡白芍药对对慢性温和不可预知性应激抑郁模型大鼠脑内单胺类神经递质的影响[J].中草药,2016,47(16):2887-2892.
[13]Menniti F S,Faraci W S,Schmidt C J.Phosphodiesterases in the CNS:Targets for drug development[J].Nat Rev Drug Discov,2006,5(8):660-670.
[14]Shelly M,Lim B K,Cancedda L,et al.Local and long-range reciprocal regulation of c AMP and c GMP in axon/dendrite formation[J].Science,2010,327(5965):547-552.
[15]Kulkarni S K,Dhir A.Current investigational drugs for major depression[J].Expert Opin Investig Drugs,2009,18(6):767-788.
[16]王景霞,刘妍,张建军.一氧化氮与抑郁症[J].现代医学,2011,39(1):104-107.
[17]张镛.神经系统的NO/c GMP系统[J].临床与病理杂志,1996,15(2):77-79.
[18]王文,徐天乐.NMDA受体通道的结构与功能[J].生物化学与生物物理进展,1997(4):321-326.
[19]中国药典[S].一部.2010.
[20]Shen J D,Ma L G,Hu C Y,et al.Berberine up-regulates the BDNF expression in hippocampus and attenuates corticosterone-induced depressive-like behavior in mice[J].Neurosci Lett,2016,614(5):77-82.
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[22]全世建,张丽君,林杏娥,等.交泰丸最优配伍比例研究[J].中医学报,2008,23(2):28-29.