醒脑开窍针刺通过Nrf2/HO-1通路对卒中后抑郁大鼠行为学和单胺类神经递质释放的影响  

Effects of acupuncture for wakening brain and opening orifices on behavioral changes and monoamine neurotransmitter release in rats with post-stroke depression through Nrf2/HO-1 pathway

作　　者：张璟婷 张弛 薄化君 张冰倩 陈文辉 ZHANG Jingting;ZHANG Chi;BO Huajun;ZHANG Bingqian;CHEN Wenhui(Shanghai Fourth People’s Hospital Affiliated to Tongji University,Shanghai 200434,China;Longhua Hospital Shanghai University of Traditional Chinese Medicine,Shang hai 200032,China)

机构地区：[1]同济大学附属上海市第四人民医院,上海200434 [2]上海中医药大学附属龙华医院,上海200032

出　　处：《现代中西医结合杂志》2024年第18期2483-2488,2495,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：上海市虹口区卫生健康委员会中医药科研项目(HKQGYQY-ZYY-2023-08);上海市虹口区第二轮“国医强优”三年行动计划(HKGYQYXM-2022-19)。

摘　　要：目的 基于核转录相关因子2 (Nrf2)/血红素加氧酶-1(HO-1)通路探讨醒脑开窍针刺对卒中后抑郁(PSD)大鼠行为学和单胺类神经递质释放的影响。方法 将60只成年雄性Sprague-Dawley大鼠随机分为假手术组、PSD组、二甲基亚砜组、醒脑开窍针刺组、醒脑开窍针刺+ML385组,每组12只。除假手术组外,其余组大鼠均采用Longa线栓法和慢性不可预知性温和应激法制备PSD模型。造模成功后,二甲基亚砜组给予40 mg/(kg·d)的二甲基亚砜灌胃,醒脑开窍针刺组给予醒脑开窍针刺干预,醒脑开窍针刺+ML385组给予醒脑开窍针刺干预和30 mg/(kg·d)的ML385灌胃,假手术组和PSD组给予等量的生理盐水灌胃,均连续干预21 d。记录各组大鼠的神经功能缺损评分,糖水偏好实验、旷场实验、强迫游泳实验评估大鼠的行为学改变,TTC染色观察脑梗死情况,HE染色观察脑组织病理形态,ELISA法检测脑组织中炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平和单胺类神经递质多巴胺(DA)、 5-羟色胺(5-HT)、去甲肾上腺素(NE)水平,Western blot法检测脑组织中Nrf2、HO-1蛋白表达情况。结果 与假手术组比较,PSD组大鼠糖水摄取百分比明显减少(P<0.05),中央探索时间明显缩短(P<0.05),强迫游泳静止时间明显延长(P<0.05);梗死灶周围脑组织出现水肿,有炎性细胞浸润;脑组织中TNF-α、IL-1β、IL-6含量均明显升高(P均<0.05),脑组织中DA、5-HT、NE含量及Nrf2、HO-1蛋白相对表达量均明显降低(P均<0.05)。与PSD组比较,醒脑开窍针刺组和醒脑开窍针刺+ML385组大鼠的神经功能缺损评分、脑梗死体积占比均明显降低(P均<0.05),糖水摄取百分比均明显增加(P均<0.05),中央探索时间均明显延长(P均<0.05),强迫游泳静止时间均明显缩短(P均<0.05);脑组织病理形态明显减轻,脑组织中TNF-α、IL-1β、IL-6含量均明显降低(P均<0.05),脑组织中DA、5-HT�Objective It is to investigate the effects of acupuncture for wakening brain and opening orifices(AWBOO)on behavioral changes and monoamine neurotransmitter release in rats with post-stroke depression(PSD)through nuclear factor-erythroid2-related factor2(Nrf2)/heme oxygenase-1(HO-1)pathway.Methods Sixty adult male Sprague-Dawley rats were randomly divided into sham operation group,PSD group,dimethyl sulfoxide(DMSO)group,AWBOO group,AWBOO+ML385 group,with 12 rats in each group.The rats of all groups except for the sham operation group were used to establish PSD models by combination of Longa suture method and chronic unpredictability mild stress method.After successful modeling,the DMSO group was given 40 mg/(kg·d)of DMSO by gavage,the AWBOO group was treated with AWBOO,the AWBOO+ML385 group was given AWBOO and 30 mg/(kg·d)of ML385 by gavage,and the sham operation group and PSD group were given an equal amount of normal saline by gavage,all of them were intervened continuously for 21 days.The neurological deficit scores of the rats in each group were recorded,the behavioral changes of the rats were evaluated by the sugar and water preference test and open field test,the cerebral infarction of the rats was observed by TTC staining,the pathological changes of the rats were observed by HE staining,the levels of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)],and the levels of monoamine neurotransmitters dopamine(DA),5-hydroxytryptamine(5-HT)and norepinephrine(NE)were detected by ELISA,and the protein expressions of Nrf2 and HO-1 in brain tissues were detected by Western blot.Results Compared with the sham operation group,the percentage of sugar-water intake of the rats in the PSD group was significantly decreased(P<0.05),their central exploratory time was significantly shortened(P<0.05),and the resting times of forced swimming was significantly increased(P<0.05);the brain tissue surrounding the infarct foci was edematous with infiltration of inflammatory cells;the

关 键 词：卒中后抑郁 醒脑开窍针刺法 核转录相关因子2 血红素加氧酶-1 单胺类神经递质 

分 类 号：R-332[医药卫生]