黄芪多糖对抑郁大鼠海马Nrf2-ARE通路的影响  

Effects of astragalus polysaccharide on depressive behaviors and hippocampal Nrf2-ARE signaling pathway in rats

作　　者：宿宏佳 王冬梅[2] 张腾 张翔 毛淑梅[1] 李承德[3] SU Hong-jia;WANG Dong-mei;ZHANG Teng;ZHANG Xiang;MAO Shu-mei;LI Cheng-de(Dept of Pharmacology,Key Lab of Applied Pharmacology in Universities of Shandong,Weifang Medical University,Weifang Shandong 261053,China;Dept of Pharmacology,Taishan Vocational College of Nursing,Taian Shandong 271000,China;Dept of Clinical Pharmacy,Key Lab of Applied Pharmacology in Universities of Shandong,Weifang Medical University,Weifang Shandong 261053,China)

机构地区：[1]潍坊医学院药理学教研室、山东省高校重点应用药理学实验室,山东潍坊261053 [2]泰山护理职业学院药理学教研室,山东泰安271000 [3]潍坊医学院临床药学教研室、山东省高校重点应用药理学实验室,山东潍坊261053

出　　处：《中国药理学通报》2021年第6期839-843,共5页Chinese Pharmacological Bulletin

基　　金：山东省自然科学基金资助项目(No ZR2020MH381,ZR2015CL029);山东省教育厅科技计划项目(No J15LL54,J16LM11);山东省中医药管理局项目(No 2015-237)。

摘　　要：目的探索黄芪多糖(astragalus polysaccharide,APS)对大鼠抑郁行为及海马组织损伤的作用,并探索其对大鼠海马Nrf2-ARE通路的影响。方法将大鼠随机分为4组:正常组、抑郁组、APS低剂量组、APS高剂量组,通过慢性应激制备抑郁模型,利用APS对大鼠进行干预。通过行为学检测评价大鼠抑郁情况,HE染色观察海马组织学病变,检测大鼠核转录因子E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)基因、Nrf2总蛋白、Nrf2核蛋白的表达,并评价大鼠海马氧化应激水平。结果与正常组比较,抑郁组大鼠出现明显的抑郁行为(P<0.05),海马组织出现病理损伤,Nrf2 mRNA、Nrf2蛋白、丙二醛(malondialdehyde,MDA)水平升高(P<0.05),而血红素氧化酶-1(heme oxygenase,HO-1)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、过氧化氢酶(catalase,CAT)水平降低(P<0.05)。与抑郁组比较,APS可改善大鼠抑郁行为及海马神经元损伤,并升高海马Nrf2 mRNA、Nrf2总蛋白、Nrf2核蛋白、SOD、GSH-Px、CAT、HO-1水平(P<0.05),降低MDA水平(P<0.05)。结论APS干预可有效改善大鼠海马损伤及抑郁行为,机制可能与激活Nrf2-ARE通路有关。Aim To investigate the effects of astragalus polysaccharide(APS)on depressive behaviors,hippocampal damage and Nrf2-ARE signaling pathway in rats.Methods Wistar rats were randomly divided into control group,depression group,APS low dose group and APS high dose group.Rats(except the control group)underwent chronic unpredictable mild stress(CUMS)for 28 days.The depressive behaviors were assessed by tail suspension test,forced swim test and sucrose preference test.The histopathological changes of the hippocampus were valuated by HE staining.Levels of nuclear factor erythroid 2-related factor 2(Nrf2)protein and Nrf2 mRNA were measured.The hippocampal levels of oxidative stress were evaluated.Results Compared with the control group,the depression group showed significant depressive behaviors and hippocampal damage.The depression group had higher levels of Nrf2 and MDA,but lower levels of HO-1,SOD,CAT and GSH-Px than the control group.However,APS does-dependently attenuated the hippocampal damage and depressive behaviors,increased hippocampal levels of Nrf2,HO-1,SOD,CAT and GSH-Px,but decreased hippocampal levels of MDA in rats.Conclusions APS can attenuate CUMS-induced hippocampal damage and depressive behaviors in rats,and the effects may be associated with the activation of Nrf2-ARE signaling pathway.

关 键 词：黄芪多糖 抗抑郁作用 海马损伤 氧化应激 SOD GSH-PX CAT MDA NRF2-ARE通路 

分 类 号：R-332[医药卫生] R284.1