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

Antidepressant effects of Jiaotai Pills based on NO-cGMP signal transduction pathway in chronic mild unpredictable stress depression rats

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.