黄芪多糖对慢性轻度不可预见性应激抑郁小鼠核因子E2相关因子2通路和血清氧化指标的影响

Effects of Astragalus polysaccharide on nuclear factor erythroid 2-related factor 2 pathway and serum oxidation indicators in mice with chronic unpredictable mild stress-induced depression

目的 探讨黄芪多糖(APS)对慢性轻度不可预见性应激(CUMS)抑郁模型小鼠核因子E2相关因子2(Nrf2)通路和血清氧化指标的影响。方法 将36只BALB/c小鼠随机分成4组:正常对照组、CUMS组、CUMS+氟西汀组(CUMS+F组)、CUMS+APS组,每组9只。CUMS、CUMS+F和CUMS+APS组小鼠采用CUMS刺激4周构建抑郁症模型。造模成功后,CUMS+F组小鼠每天给予氟西汀10 mg/kg腹腔注射,CUMS+APS组小鼠每天给予APS 400 mg/kg灌胃,正常对照组和CUMS组给予等体积的生理盐水,共干预治疗4周。通过行为学实验观察药物干预后小鼠抑郁状态是否改善。小鼠药物干预4周后经眼眶取血,采用ELISA检测血清丙二醛、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、超氧阴离子■、羟自由基(·OH)水平。采用蛋白质印迹法检测小鼠海马组织中Nrf2蛋白的表达。结果 与CUMS组比较,CUMS+F组和CUMS+APS组小鼠悬尾实验不动时间缩短(P均<0.01),蔗糖偏好率、旷场实验穿越次数、高架十字迷宫实验开放臂的进入次数和停留时间均增加(P<0.05,P<0.01);小鼠血清丙二醛含量下降(P均<0.05),SOD、GSH-Px、■和·OH含量升高(P<0.05,P<0.01);小鼠海马组织中Nrf2蛋白表达水平升高(P<0.05,P<0.01)。结论 APS对CUMS抑郁模型小鼠的抑郁状态具有改善作用,其作用可能是通过调节海马组织Nrf2通路和血清中的氧化指标实现的。

Objective To explore the effects of Astragalus polysaccharide(APS)on nuclear factor erythroid 2-related factor 2(Nrf2)pathway and serum oxidation indicators in chronic unpredictable mild stress(CUMS)-induced depression model mice.Methods Thirty-six BALB/c mice were randomly assigned to normal control group,CUMS group,CUMS+fluoxetine group(CUMS+F group),or CUMS+APS group,with 9 mice in each group.The mice in the CUMS,CUMS+F and CUMS+APS groups were stimulated by CUMS for 4 weeks to construct depression models.After successful modeling,the mice in the CUMS+F group were intraperitoneally injected with 10 mg/kg of fluoxetine daily,the mice in the CUMS+APS group were given 400 mg/kg of APS by gavage daily,and the mice in the normal control group and CUMS group were given an equal volume of normal saline for 4 weeks.The depression status of the mice was observed by behavioral experiment after drug intervention.After 4 weeks of drug intervention,the eye socket blood was collected,and the levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),superoxide anion(O_(2))and hydroxyl radical(·OH)in the mouse serum were detected using enzyme-linked immunosorbent assay.The expression of Nrf2 in mouse hippocampal tissue was detected by Western blotting.Results Compared with the CUMS group,the immobility time of mice was significantly shortened in the CUMS+F group and CUMS+APS group in the tail suspension experiment(both P<0.01),while the sucrose preference rate,crossing times of open-field test,and the entry times of open arm and time spent in open arm in the elevated cross maze experiment were significantly increased(P<0.05,P<0.01);the level of MDA in the mouse serum was significantly decreased(both P<0.05),while the levels of SOD,GSH-Px,and·OH were significantly increased(P<0.05,P<0.01);and the expression level of Nrf2 in the mouse hippocampal tissue was significantly increased(P<0.05,P<0.01).Conclusion APS can improve the depressive state of CUMS-induced depression model mice,which may be achieved by regulating Nrf2 pathway in hippocampal tissue and serum oxidative indicators.