药对刺五加栀子对慢性应激抑郁模型大鼠大脑PKC-IP_3信号通路的影响

Influence of Couplet Medicines with Ciwujia [Acanthopanax senticosus( Rupr. Maxim. ) Harms]and Zhizi[Gardenia jasminoides Ellis]on PKC-IP3 signaling pathway in Chronic Stress Depression Model Rats

目的探讨药对刺五加-栀子治疗抑郁症的可能作用机制。方法将大鼠随机分为空白组、模型组、刺五加-栀子组和氟西汀组,每组10只。除空白组外,其余各组大鼠均采用慢性温和不可预见性刺激结合孤养的方法制备抑郁模型,造模3周后氟西汀组给予氟西汀胶囊溶液1.8 mg/(kg·d)灌胃,刺五加-栀子组给予药对刺五加-栀子溶液2.16 g/(kg·d)灌胃,正常组和模型组灌胃等体积的生理盐水。每日1次,连续给药28天。检测大鼠海马和额叶皮层中鸟嘌呤核苷酸偶联蛋白(GIα)表达及蛋白激酶C(PKC)、三磷酸肌醇(IP3)含量。结果与空白组比较,模型组大鼠海马和额叶皮层中GIα、PKC、IP3含量显著增加(P<0.01)。与模型组比较,氟西汀组、刺五加-栀子组大鼠海马和额叶皮层中GIα、PKC、IP3含量降低(P<0.01)。结论药对刺五加-栀子可能通过调节慢性应激抑郁大鼠大脑PKC-IP3信号通路,从而发挥抗抑郁作用。

Objective To explore the possible mechanism of couplet medicines with Ciwujia [Acanthopanax senticosus（ Rupr. Maxim.） Harms]and Zhizi [Gardenia jasminoides Ellis]in treating depression. Methods Rats were randomized into blank group,model group,Ciwujia-Zhizi group and Fluoxetine group,with 10 rats in each group. The depression model was built by chronic mild unpredictable stress and separation except for the blank group.After 3 weeks of modeling,the Fluoxetine group was given Fluoxetine capsules 1. 8 mg/（ kg · d） by gavage; the Ciwujia-Zhizi group was given couplet medicines Ciwujia and Zhizi 2. 16 g/（ kg·d） by gavage; the blank group and the model group were given equivalent normal saline by gavage. The medicine was given once a day for continuous 28 days. Then the levels of GIα,protein kinase C（ PKC） and inositol triphosphate（ IP3） in hippocampus and frontal cortex of rats were detected. Results Compared with the blank group,the levels of GIα,PKC and IP3 in the hippocampus and frontal cortex in the model group were significantly higher（ P〈0. 01）. Compared with the model group,the levels of GIα,PKC and IP3 in the hippocampus and frontal cortex in Fluoxetine group and Ciwujia-Zhizi group were significantly lower（ P〈0. 01）. Conclusion The couplet medicines Ciwujia and Zhizi might play the antidepressant role by regulating the PKC-IP3 signaling pathway in chronic stress depression rat models.