[1]韩萌蕊,胡馨念,宋佳璇,等.川芎嗪调控腺苷酸活化蛋白激酶对慢性偏头痛大鼠的作用机制[J].陕西中医,2025,46(7):870-874.[doi:DOI:10.3969/j.issn.1000-7369.2025.07.002]
　HAN Mengrui,HU Xinnian,SONG Jiaxuan,et al.Mechanism of tetramethylpyrazine regulating adenylate activated protein kinase on chronic migraine rats[J].,2025,46(7):870-874.[doi:DOI:10.3969/j.issn.1000-7369.2025.07.002]
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川芎嗪调控腺苷酸活化蛋白激酶对慢性偏头痛大鼠的作用机制

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
46
期数:
2025年7期
页码:
870-874
栏目:
基础研究
出版日期:
2025-07-05

文章信息/Info

Title:
Mechanism of tetramethylpyrazine regulating adenylate activated protein kinase on chronic migraine rats
作者:
韩萌蕊; 胡馨念; 宋佳璇; 房冰莹; 侯淑珍; 王海芳; 张鑫强; 刘晓华
（陕西中医药大学，陕西 咸阳 712046）
Author(s):
HAN Mengrui; HU Xinnian; SONG Jiaxuan; FANG Bingying; HOU Shuzhen; WANG Haifang; ZHANG Xinqiang; LIU Xiaohua
(Shaanxi University of Chinese Medicine,Xianyang 712046,China)
关键词:
慢性偏头痛; 川芎嗪; 腺苷酸活化蛋白激酶; 能量代谢; 痛觉相关分子; 炎症因子
Keywords:
Chronic migraine; Tetramethylpyrazine; Adenylate-activated protein kinase; Energy metabolism; Nociception-related molecules; Inflammatory factors
分类号:
R 285.5
DOI:
DOI:10.3969/j.issn.1000-7369.2025.07.002
文献标志码:
A
摘要:
目的：基于腺苷酸活化蛋白激酶（AMPK）探讨川芎嗪对慢性偏头痛的治疗机制。方法：30只健康雄性SD大鼠随机分为对照组、模型组、川芎嗪给药组，每组10只。除对照组外，其余各组大鼠皮下注射硝酸甘油建立慢性偏头痛模型。川芎嗪给药组给予川芎嗪 200 mg/（kg·d）灌胃，对照组、模型组给予0.9%氯化钠溶液灌胃，连续干预9 d。利用Von Frey纤毛测定大鼠眼眶周围机械痛阈值；一氧化氮（NO）检测试剂盒测定大鼠血清、脑脊液中NO水平；三磷酸腺苷(ATP）检测试剂盒测定大鼠三叉神经节（TG）中ATP含量；RT-PCR检测大鼠TG中即刻早期基因（c-Fos）、降钙素基因相关肽（CGRP）、肿瘤坏死因子-α（TNF-α）、诱导型NO合成酶（iNOS）、腺苷酸活化蛋白激酶A（Prkaa）mRNA表达水平。AutoDock Tools-1.5.7软件进行分子对接，预测川芎嗪与AMPK结合位点。结果：与对照组比较，模型组大鼠机械痛阈值、TG中ATP含量、Prkaa mRNA水平降低，而血清NO、TG中c-Fos、CGRP、TNF-α、iNOS mRNA显著升高（均P＜0.05）。与模型组比较，川芎嗪给药组大鼠机械痛阈值、TG中ATP含量、Prkaa mRNA水平升高，血清NO水平、TG中c-Fos、CGRP、TNF-α、iNOS mRNA水平降低（均P＜0.05）。川芎嗪可与AMPK多个位点对接，其中的2H6D位点组氨酸（His）73残基结合力最强。结论：川芎嗪对慢性偏头痛具有镇痛治疗作用，其机制可能是通过调控初级感觉神经元AMPK表达或直接与AMPK结合，促进细胞能量代谢，抑制iNOS、TNF-α和CGRP等痛觉及炎症相关介质释放。
Abstract:
Objective:To investigate therapeutic effect of tetramethylpyrazine on chronic migraine and its mechanism based on adenylate-activated protein kinase (AMPK).Methods:Thirty healthy male SD rats were randomly divided into the control,model,and tetramethylpyrazine administration groups,with 10 rats in each group.Except for the control group,the rats in each group were injected subcutaneously with nitroglycerin to establish chronic migraine model.The tetramethylpyrazine-administered group were given tetramethylpyrazine 200 mg/(kg·d) by gavage,while the control and model groups were given 0.9% sodium chloride solution by gavage for 9 consecutive days.Von frey cilia were used to determine the periorbital mechanical pain threshold of rats.Nitric oxide (NO) assay kit was used to determine the NO level in serum and cerebrospinal fluid.Adenosine triphosphate (ATP) assay kit was used to determine the ATP content of the trigeminal ganglion (TG).RT-PCR was used to detect immediate early gene (c-Fos),calcitonin gene-related peptide (CGRP),and tumor necrosis factor-α (TNF-α) in the TG of rats.Tetramethylpyrazine TNF-α,inducible NO synthase (iNOS),and adenylate-activated protein kinase A (Prkaa) mRNA expression levels in the TG of the rats.AutoDock Tools-1.5.7 software was used to carry out molecular docking to predict binding sites of tetramethylpyrazine and AMPK.Results:Compared with the control group,rats in the model group showed decreased mechanical pain threshold,ATP content in TG,Prkaa mRNA level,and significantly increased serum NO level,c-Fos,CGRP,TNF-α,iNOS mRNA level in TG (all P＜0.05).Compared with the model group,rats in the tetramethylpyrazine administration group showed increased mechanical pain threshold,ATP content in TG,Prkaa mRNA levels were elevated,and serum NO levels,c-Fos,CGRP,TNF-α,and iNOS mRNA levels in TG were significantly reduced (all P＜0.05).Tetramethylpyrazine could dock with multiple sites of AMPK,among which it had the strongest binding force with residue 73 of histidine (His) at the 2H6D site.Conclusion:Tetramethylpyrazine has analgesic therapeutic effects on chronic migraine.Its mechanism may be to promote cellular energy metabolism by modulating the expression of AMPK in primary sensory neurons or directly binding to AMPK,as well as inhibiting the release of nociceptive and inflammation-related mediators such as iNOS,TNF-α,and CGRP.

参考文献/References:

[1]叶深琼，王相明，张月辉.偏头痛发病机制的研究进展[J].医学综述，2020，26(6):1086-1091.
[2]YU S，LIU R，ZHAO G，et al.The prevalence and burden of primary headaches in China:A population-based door-to-door survey[J].Headache:The Journal of Head and Face Pain，2012，52(4):582-591.
[3]崔雁龙，林进，曲崇正，等.穴位埋线治疗偏头痛临床疗效Meta分析[J].陕西中医，2022，43(12):1809-1815.
[4]王鲁扬，刘源香.中医外治法治疗偏头痛疗效Meta分析[J].陕西中医，2023，44(11):1640-1645.
[5]樊志丽，嵇冰.偏头痛的中医防治研究进展[J].内蒙古中医药，2022，41(9):141-142.
[6]张衙楠，冯晨晨，董馨，等.脑能量代谢失衡在慢性疼痛中的研究进展[J].中国疼痛医学杂志，2023，29(6):443-447.
[7]王锋，秦文秀，王琪，等.AMPK调控铁死亡相关信号通路的研究现状[J].中国药理学通报，2023，39(10):1801-1805.
[8]张宸崧，王子涵，陈燕雯，等.单磷酸腺苷激活的蛋白激酶（AMPK):能量、葡萄糖感受器和代谢性疾病治疗靶标[J].厦门大学学报，2022，61(3):325-345.
[9]HERZIG S，SHAW R J.AMPK guardian of metabolism and mitochondrial homeostasis[J].Nature Reviews Molecular Cell Biology，2018，19(2):121-135.
[10]张可，李元亨，王随曦，等.AMPK参与调控疼痛机制的研究进展[J].中国疼痛医学杂志，2023，29(1):6-11.
[11]徐榛敏，贾敏，梁晓，等.偏头痛中医临床实践指南[J].中国中药杂志，2020，45(21):5057-5067.
[12]于新，柴军红，孔祥文，等.基于归经理论指导下川芎治疗头痛的研究进展[J].中医药学报，2023，51(2):113-120.
[13]彭涛，张慧，杨一帆，等.川芎及其方剂抗偏头痛的药理学研究进展[J].中草药，2024，55(3):1004-1013.
[14]刘英，程敏菊，魏鹏辉.川芎嗪缓解冠心病大鼠心肌损伤的作用及其机制[J].西北药学杂志，2023，38(3):62-67.
[15]MOYE L S，PRADHAN A A A.Animal model of chronic migraine-associated pain[J].Current Protocols in Neuroscience，2017，80(1):1-9.
[16]肖萧，陈春富.线粒体能量代谢障碍在偏头痛发病中的作用[J].国际神经病学神经外科学杂志，2014，41(3):280-284.
[17]李德新，刘燕池.中医基础理论[M].北京:人民卫生出版社，2011:641.
[18]金海娣，潘梦雄，陈媚娇，等.偏头痛脑能量代谢机制[J].中国现代神经疾病杂志，2022，22(2):73-77.
[19]DONG X，GUAN X，CHEN K，et al.Abnormal mitochondrial dynamics and impaired mitochondrial biogenesis in trigeminal ganglion neurons in a rat model of migraine[J].Neuroscience Letters，2017，636:127-133.
[20]FENG F，XU D Q，YUE S J，et al.Neuroprotection by tetramethylpyrazine and its synthesized analogues for central nervous system diseases:A review[J].Molecular Biology Reports，2024，51(1):159.
[21]胡坤.川芎白芍不同配比对偏头痛模型痛阈和三叉神经血管通路c-fos、pCREB的影响[D].北京:北京中医药大学，2018.
[22]WATTIEZ A S，SOWERS L P，RUSSO A F.Calcitonin gene-related peptide (CGRP):Role in migraine pathophysiology and therapeutic targeting[J].Expert Opinion on Therapeutic Targets，2020，24(2):91-100.
[23]EDVINSSON L.Neuronal signal substances as biomarkers of migraine[J].Headache:The Journal of Head and Face Pain，2006，46(7):1088-1094.
[24]刘长安，朱洁，蔡标，等.川芎嗪通过AMPK-NFκB信号通路抑制BV-2小胶质细胞促炎性细胞因子基因表达[J].安徽中医药大学学报，2014，33(3):76-80.
[25]张国浩，王君君，杨丽，等.清热通痹汤联合微创针刀镜治疗膝关节痛风性关节炎的疗效及对血清环氧化酶-2、一氧化氮的影响[J].河北中医，2023，45(11):1837-1840.
[26]郭琳，洪治平.硝酸甘油型实验性偏头痛模型原理与研究现状[J].中国疼痛医学杂志，2004，10(6):357-359,364.
[27]刘斌，马原源，毛文静，等.偏头痛模型大鼠血浆一氧化氮和降钙素基因相关肽含量变化及氟桂利嗪干预效果实验研究[J].陕西医学杂志，2020，49(7):771-773.
[28]张磊,张国庆,李梦,等.“通督调神”法针刺联合前庭康复训练治疗前庭性偏头痛疗效研究[J].陕西中医,2025,46(3):412-415.
[29]黄国清.分级护理在急性酒精中毒患者护理中的应用效果[J].保健医学研究与实践,2022,19(11):99-102.
[30]周天志,尹敏,姚磊.经胸右心声学造影对偏头痛卵圆孔未闭患者右向左分流及分流程度的检测价值研究[J].陕西医学杂志,2024,53(5):650-653.

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（82004221）；陕西省教育厅重点实验室项目（23JS005）；陕西中医药大学大学生创新训练计划项目（S202310716042）
更新日期/Last Update: 2025-07-09