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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
袁前发,徐志忠,温春燕,张贤华,林多朵,王文强*
0
(厦门市仙岳医院(厦门医学院附属仙岳医院)精神卫生研究室, 福建省精神医学中心, 福建省精神疾病临床医学研究中心, 厦门 361012
*通信作者)
摘要:
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(O2·)、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、O2·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。
关键词:  黄芪多糖  抑郁症  慢性轻度不可预见性应激  氧化  核因子E2相关因子2
DOI:10.16781/j.CN31-2187/R.20220835
投稿时间:2022-10-27修订日期:2023-04-06
基金项目:国家自然科学基金(81871058),福建省卫生健康青年科研项目(2019-2-54),厦门市医疗卫生指导性项目(3502Z20199092).
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
YUAN Qianfa,XU Zhizhong,WEN Chunyan,ZHANG Xianhua,LIN Duoduo,WANG Wenqiang*
(Mental Health Research Laboratory, Xiamen Xianyue Hospital (Xianyue Hospital Affiliated to Xiamen Medical College) & Fujian Psychiatric Center & Fujian Clinical Research Center for Mental Disorders, Xiamen 361012, Fujian, China
*Corresponding author)
Abstract:
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 (O2·) 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,O2· 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.
Key words:  Astragalus polysaccharide  depressive disorder  chronic unpredictable mild stress  oxidation  nuclear factor erythroid 2-related factor 2