栀子苷对抑郁模型大鼠前额叶脑衰反应蛋白2表达的影响及其潜在分子机制

Effects of Gardeniin on the Expression of Collapsin Response Mediator Protein 2 and Potential Molecular Mechanism in Prefrontal Cortex of Depression Model Rats

目的:观察慢性温和应激(CMS)抑郁模型大鼠前额叶哺乳动物雷帕霉素靶蛋白(mTOR)、S6K和脑衰反应蛋白2(CRMP2)的表达变化,并探讨栀子苷抗抑郁作用的机制。方法:40只雄性Wistar大鼠随机平均分为4组:正常对照组、模型组、氟西汀组(阳性对照,5 mg·kg^(-1)·d^(-1))和栀子苷组(50 mg·kg^(-1)·d^(-1))。正常对照组予以常规饲养,其余各组建立大鼠CMS抑郁症模型。造模28 d后,氟西汀组和栀子苷组灌胃给与相应药物,正常对照组和模型组给与等量生理盐水,1次/d,持续14 d,给药期间各组大鼠均继续给予CMS。给药结束后进行糖水偏好实验、旷场实验和强迫游泳实验行为学检测;分别采用RT-qPCR和Western blot检测前额叶m-TOR、S6K、CRMP2 mRNA和蛋白表达。结果:模型组大鼠表现出明显的抑郁样行为,前额叶m-TOR、S6K和CRMP2表达显著降低,与正常对照组比较,差异有统计学意义(P<0.01);经药物治疗后,CMS大鼠的抑郁样行为明显减少,前额叶m-TOR、S6K和CRMP2表达抑制被显著逆转(P<0.05或P<0.01)。结论:前额叶m-TOR/S6K/CRMP2信号抑制介导CMS大鼠抑郁样行为的发生,栀子苷可以缓解CMS大鼠抑郁样行为,同时逆转CMS所致的前额叶m-TOR、S6K和CRMP2的低表达。

Objective:To observe the expression changes of mammalian target of rapamyoin(mTOR),S6 K and collapsin response mediator protein 2(CRMP2)in prefrontal cortex of chronic mild stress(CMS)depression model rats,and to explore the mechanism of antidepressant effects of gardenoside.Methods:Totally 40 adult male Wistar rats were divided into 4 groups randomly and averagely:normal control group,model group,fluoxetine group(positive control,5 mg·kg^(-1)·d^(-1))and gardenoside group(50 mg·kg^(-1)·d^(-1)).Normal control group was given conventional feeding,and the other groups were established CMS model.On the 28 th day after modeling,fluoxetine group and jasminoside group were given corresponding drugs by intragastric administration,and control group and model group were given the same amount of normal saline once a day for 14 d,and all rats were given CMS.After drug administration,sucrose preference test,open field test and forced swimming test were performed,the mRNA and protein expressions of m-TOR,S6 K and CRMP2 in prefrontal cortex were detected by RT-qPCR and Western blot.Results:The rats in the model group exhibited significant depression-like behaviors,and the expressions of m-TOR,S6 K and CRMP2 in prefrontal cortex were significantly decreased,and as compared with the normal control group,the differences were statistically significant(P<0.01);after drug treatment,CMS rats showed a significant reduction in depression-like behavior,and the decreased expressions of m-TOR,S6 K and CRMP2 in prefrontal cortex of CMS rats were significantly reversed(P<0.05 or P<0.01).Conclusion:Suppression of prefrontal m-TOR/S6 K/CRMP2 signal mediates the occurrence of depression-like behavior in CMS rats.Geniposide can relieve depression-like behavior of CMS rats and reverse the low expressions of m-TOR,S6 K and CRMP2 induced by CMS in prefrontal cortex.