人参皂苷Rg1对CUMS+LPS致小鼠抑郁行为的改善作用及其机制

Ameliorative Effects of Ginsenoside Rg1 on CUMS+LPS Induced Depressive-Like Behavior and Its Mechanisms in Mice

为了探讨人参皂苷Rg1对抑郁小鼠的保护作用及其机制,本实验建立了慢性轻度不可预知性刺激(CUMS)+脂多糖(LPS)致小鼠抑郁模型。将雄性C57BL/6J小鼠随机分为对照组、模型组、米诺环素组、Rg15mg/kg、Rg110 mg/kg和Rg120 mg/kg组,模型组与给药组连续给予11 d的慢性轻度不可预知性刺激(CUMS),同时每天腹腔注射给予溶媒和相应药物,末次给药后1 h,腹腔注射LPS 200μg/kg,24 h后通过悬尾实验和强迫游泳实验评价动物抑郁状态,旷场实验评价Rg1对小鼠自主活动的影响;液相色谱-质谱联用(LC-MS)检测不同脑区多巴胺(DA)、去甲肾上腺素(NE)水平,ELISA检测前额叶皮质和血清中肿瘤坏死因子(TNF-α)及血清中促肾上腺皮质激素(ACTH)、皮质酮(CORT)水平;Western blot检测海马NF-κB P65、FKBP51、GR蛋白表达。结果显示,Rg1能显著缩短抑郁小鼠悬尾不动时间及游泳不动时间;提高抑郁小鼠不同脑区DA、NE水平同时降低抑郁小鼠前额叶皮质和血清TNF-α以及血清ACTH和CORT水平;下调抑郁小鼠海马NF-κB P65、FKBP51蛋白以及上调GR蛋白表达。结果提示,Rg1可能通过上调GR表达,降低HPA轴过度兴奋、抑制中枢炎症反应,发挥抗抑郁作用。

A C57BL/6J mouse model of depression induced by unpredictable chronic mild stress plus LPS is established to investigate the protection and mechanism of ginsenside Rg1.C57BL/6J mice are randomly divided into control group,model group,minocycline group,Rg15 mg/kg group,Rg110 mg/kg group,and Rg120 mg/kg group.The mice in the model group and the administration group are subject to CUMS for 11 d by using variety of stressors.Vehicle and corresponding drugs are administrated intraperitoneally every day.LPS(200μg/kg)is given intraperitoneally 1 h after the last dose.After giving LPS 24 h,the tail suspension test(TST),forced swimming test(FST)and open field test(OFT)are performed to evaluate depressive-like behavior in animals and spontaneous locomotor activity of mice,respectively.Moreover,LC-MS is used to detect the levels of DA and NE in different brain regions.The levels of TNF-αin prefrontal cortex and serum as well as ACTH and CORT in serum are detected by ELISA.Western blotting is used to detect the protein expression of FKBP51,GR and NF-κB P65 in hippocampus.The results show that Rg1 significantly decreases the immobility time of depression-like mice in TST and FST,but increases DA and NE levels in different brain regions and reduces TNF-αin prefrontal cortex and ACTH and CORT in serum.Western blotting show that Rg1 significantly decreases nuclear NF-κB p65,FKBP51 protein expression and increases GR protein expression in the hippocampus.In conclusion,Rg1 has a good antidepressant effects on C57BL/6J mice,and its mechanism may be associated with the up-regulation of GR expression,decreasing hyperactivity of the HPA axis,inhibiting peripheral and central inflammatory responses.