阿纳其根醇提物通过CREB/BDNF信号轴改善 围绝 经期抑郁的机制研究  

Mechanism of Ethanol Extract of Anacyclus Pyrethrum Root in Improving Perimenopausal Depression Through CREB/BDNF Signaling Axis

作　　者：买热木古·阿布都热依木 塔依尔·吐尔松 杨烨 MAIREMUGU Abudureyimu;TAYI’ER Tuersong;YANG Ye(Dept.of Geriatrics(Cadre Section 1),the Second Affiliated Hospital of Xinjiang Medical University,Urumqi 830063,China;Dept.of Clinical Pharmacy,the Second Affiliated Hospital of Xinjiang Medical University,Urumqi 830063,China)

机构地区：[1]新疆医科大学第二附属医院老年科(干部一科),乌鲁木齐830063 [2]新疆医科大学第二附属医院临床药学室,乌鲁木齐830063

出　　处：《中国医院用药评价与分析》2025年第4期407-411,共5页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：新疆维吾尔自治区自然科学基金资助项目(No.2023D01C419)。

摘　　要：目的:探讨阿纳其根醇提物通过环磷酸腺苷应答元件结合蛋白质(CREB)/脑源性神经生长因子(BDNF)信号轴对围绝经期抑郁模型大鼠的神经保护效应及抗抑郁作用机制。方法:采用双侧卵巢切除联合慢性不可预知性温和应激法制备大鼠围绝经期抑郁模型,将实验动物随机分为假手术组、模型组、阳性药组(氟西汀2 mg/kg+雌激素0.15 mg/kg)和阿纳其根醇提物组(低、中及高剂量组分别给药10、20及40 mg/kg),每组8只,连续治疗21 d。观察各组大鼠行为学变化,利用旷场实验和强迫游泳实验对给药后大鼠行为学变化进行评价。采用酶联免疫吸附试验检测大鼠血清5-羟色胺(5-HT)和环磷酸腺苷(cAMP)水平变化,采用定量聚合酶链反应(qPCR)测定大鼠海马组织中BDNF和CREB的mRNA表达,采用免疫组织化学分析和蛋白质印迹法测定大鼠海马组织中CREB、BDNF的蛋白表达。结果:与假手术组比较,模型组大鼠表现出抑郁样行为,主要为自主活动及探索活动减少,强迫游泳不动时间延长,血清5-HT、cAMP含量降低;与模型组比较,阿纳其根醇提物组大鼠抑郁样行为改善,自主活动及探索活动能力提高,强迫游泳不动时间缩短,血清5-HT、cAMP含量升高,海马组织中CREB、BDNF的mRNA和蛋白表达水平升高;各剂量组组间比较,阿纳其根醇提物高剂量组上述指标改善更明显,差异均有统计学意义(P<0.05)。结论:阿纳其根醇提物对围绝经期抑郁模型大鼠的抑郁样行为具有改善作用,其作用机制主要与增加血清5-HT和cAMP含量有关,还与上调CREB和BDNF的蛋白表达有关。本研究对阐明阿纳其根醇提物在围绝经期抑郁治疗中的分子机制、揭示围绝经期抑郁发生、发展机制及实现其临床治疗均具有重要的价值。OBJECTIVE:To investigate the neuroprotective and antidepressant effects of anacyclus pyrethrum root ethanol extract on perimenopausal depression model rats through cyclic adenosine phosphate response element binding protein(CREB)/brain-derived nerve growth factor(BDNF)signaling axis.METHODS:The rat model of perimenopausal depression was prepared by bilateral ovariectomy combined with chronic unpredictable mild stress.The experimental animals were randomly divided into the sham operation group,model group,positive drug group(fluoxetine 2 mg/kg+estrogen 0.15 mg/kg)and ethanol extract of anacyclus pyrethrum root group(low,medium and high dose groups were respectively given 10 mg/kg,20 mg/kg and 40 mg/kg),with 8 cases in each group and continuous treatment for 21 d.The behavioral changes of rats in each group were observed,and the behavioral changes of rats after administration were evaluated by open field test and forced swimming test.The changes of 5-hydroxytryptamine(5-HT)and cyclic adenosine monophosphate(cAMP)in serum of rats were detected by enzyme-linked immunosorbent assay.The mRNA expression levels of BDNF and CREB in hippocampus were determined by quantitative PCR(qPCR).Immunohistochemical analysis and Western blotting were used to detect CREB and BDNF in hippocampus of rats.RESULTS:Compared with the sham operation group,rats in the model group showed depressive-like behaviors,mainly including decreased autonomous and exploratory activities,prolonged behavioral despair time,and decreased serum 5-HT and cAMP levels;compared with the model group,the depression-like behavior of theethanol extract of anacyclus pyrethrum root group was improved,the ability of autonomous and exploratory activities was improved,the behavioral despair time was shortened,the serum 5-HT and cAMP levels increased,and the mRNA and protein expression levels of CREB and BDNF in hippocampus increased;among all dose groups,the improvement of the above indicators was more obvious in the high-doseethanol extract of anacyclus pyrethrum root g

关 键 词：围绝经期抑郁 阿纳其根醇提物 环磷酸腺苷应答元件结合蛋白质/脑源性神经生长因子信号轴 5-羟色胺 环磷酸腺苷 

分 类 号：R96[医药卫生—药理学] R932[医药卫生—药学]