白杨素抑制大鼠脑缺血/再灌注损伤后氧化应激和过度自噬的机制研究  

Effect of Chrysin on Inhibiting Oxidative Stress and Excessive Autophagy after Cerebral Ischemia/Reperfusion Injury in Rats

作　　者：张方[1] 李文杰[1] 董永书[2] 韩东[1] 王东晓[1] ZHANG Fang;LI Wenjie;DONG Yongshu;HAN Dong;WANG Dongxiao(The Second People′s Hospital of Jiaozuo,Jiaozuo 454100,Henan,China)

机构地区：[1]焦作市第二人民医院,河南焦作454100 [2]河南省中医药研究院附属医院

出　　处：《中西医结合心脑血管病杂志》2023年第23期4334-4339,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

摘　　要：目的:研究白杨素对脑缺血再灌注(CI/RI)大鼠脑组织氧化应激损伤和自噬的缓解作用。方法:45只Sprague-Dawley(SD)大鼠随机分为Sham组、Model组、白杨素50 mg/kg组、白杨素100 mg/kg组、尼莫地平10 mg/kg组。除Sham组外,其他各组建立CI/RI大鼠模型。白杨素50 mg/kg组、白杨素100 mg/kg组分别给予白杨素50、100 mg/kg灌胃,每日1次;尼莫地平10 mg/kg组腹膜内注射尼莫地平10 mg/kg,每日1次;Sham组、Model组给予等量生理盐水灌胃,每日1次,连续干预7 d。Y迷宫实验评价各组大鼠行为学;苏木素-伊红(HE)染色观察脑组织病理损伤;试剂盒检测总抗氧化能力(T-AOC)、过氧化氢酶(CAT)和过氧化氢(H_(2)O_(2))、谷胱甘肽过氧化物酶(GSH-Px)、还原性谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和丙二醛(MDA);蛋白免疫印迹法(Western Blot)检测自噬标志蛋白Beclin-1和微管相关蛋白轻链3-Ⅱ(LC3-Ⅱ)表达水平及核因子E2相关因子2(Nrf2)/血红素氧合酶-1(HO-1)通路蛋白表达水平。结果:与Sham组比较,Model组大鼠Y迷宫实验检测新异臂进入次数明显降低(P<0.01);脑组织细胞摆列状态散乱;T-AOC和CAT活力明显下降,SOD和GSH活性明显降低,而H_(2)O_(2)与MDA含量明显上升(P<0.01);LC3-Ⅱ、Beclin-1、Nrf2和HO-1的蛋白表达水平明显升高(P<0.05)。与Model组比较,白杨素治疗明显改善脑组织病理损伤和增加新异臂进入次数(P<0.05);T-AOC和CAT活力明显增加,SOD和GSH活性明显上升,而H_(2)O_(2)与MDA含量明显下降(P<0.05);LC3-Ⅱ、Beclin-1、Nrf2和HO-1的蛋白表达水平明显降低(P<0.05)。结论:白杨素治疗可抑制CI/RI损伤引起的机体氧化应激和自噬,其潜在机制或与白杨素对Nrf2/HO-1通路的活化有关。Objective:To study the mitigation effects of chrysin on oxidative stress injury and autophagy in cerebral ischemia reperfusion(CI/RI)rats.Methods:Forty-five Sprague-Dawley(SD)rats were randomly divided into Sham group,Model group,chrysin 50 mg/kg group,chrysin 100 mg/kg group,nimodipine 10mg/kg group.CI/RI rat models were established in other groups except Sham group.Chrysin 50 mg/kg group and chrysin 100 mg/kg group were given chrysin 50 and 100 mg/kg intragastric administration,once a day,respectively.Nimodipine 10 mg/kg group was intraperitoneally injected with nimodipine 10 mg/kg once a day.Sham group and Model group were given same volume of normal saline once a day.After continuous intervention for 7 days.Y Maze experiment was used to evaluate the behavior of rats in each group.Hematoxylin-eosin(HE)staining was used to observe the pathological injury of cerebral tissue.Total antioxidant capacity(T-AOC),catalase(CAT)and hydrogen peroxide(H_(2)O_(2)),glutathione peroxidase(GSH-Px),glutathione(GSH),superoxide dismutase(SOD),and malondialdehyde(MDA)were detected by the kit.Western Blot analysis was performed to detect the expression levels of Beclin-1,microtubule-associated protein light chain 3-Ⅱ(LC3-Ⅱ)and nuclear factor E2-related factor(Nrf2)/heme oxygenase 1(HO-1)pathway proteins.Results:Compared with the Sham group,Y maze test of Model group the number of new arm entry significantly reduced(P<0.01).Cerebral tissue cells arranged in a disorganized state.The activities of T-AOC and CAT significantly decreased,the activities of SOD and GSH significantly decreased,and the contents of H_(2)O_(2)and MDA significantly increased(P<0.05 or P<0.01).The protein expression levels of LC3-Ⅱ,Beclin-1,Nrf2 and HO-1 significantly increased(P<0.05).Compared with the Model group,chrysin treatment significantly improved the pathological injury of cerebral tissue and increased the entry times of new arm(P<0.05 or P<0.01).The activities of T-AOC and CAT significantly increased,the activities of SOD and GSH significantly i

关 键 词：脑缺血再灌注损伤 白杨素 微管相关蛋白轻链3-Ⅱ Y迷宫实验 BECLIN-1 

分 类 号：R285.5[医药卫生—中药学]