[1]黄娜,李静,祁天培,等.Th1/Th2免疫失衡介导的JAK2/STAT3信号通路在慢性偏头痛模型大鼠神经递质释放中的作用机制[J].卒中与神经疾病杂志,2024,31(05):465-469.[doi:10.3969/j.issn.1007-0478.2024.05.008]
 Huang Na*,Li Jing*,Qi Tianpei,et al.Mechanism of JAK2/STAT3 signaling pathway mediated by Th1/Th2 immune imbalance in neurotransmitter release in chronic migraine model rats[J].Stroke and Nervous Diseases,2024,31(05):465-469.[doi:10.3969/j.issn.1007-0478.2024.05.008]
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Th1/Th2免疫失衡介导的JAK2/STAT3信号通路在慢性偏头痛模型大鼠神经递质释放中的作用机制()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第31卷
期数:
2024年05期
页码:
465-469
栏目:
论著
出版日期:
2024-10-20

文章信息/Info

Title:
Mechanism of JAK2/STAT3 signaling pathway mediated by Th1/Th2 immune imbalance in neurotransmitter release in chronic migraine model rats
文章编号:
1007-0478(2024)05-0465-05
作者:
黄娜李静祁天培柴琳洁李琳
073000 河北省定州市人民医院中医科[黄娜 李静(通信作者)]; 廊坊市卫生急救中心直属急救站(祁天培); 石家庄市藁城人民医院(柴琳洁 李琳)
Author(s):
Huang Na* Li Jing* Qi Tianpei et al.
*Department of Traditional Chinese Medicine, Dingzhou People's Hospital, Dingzhou Hebei 073000
关键词:
慢性偏头痛 非受体型蛋白酪氨酸激酶2/转录激活因子3信号通路 神经递质
Keywords:
Chronic migraine JAK2/STAT3 signaling pathway Neurotransmitter
分类号:
R747.2
DOI:
10.3969/j.issn.1007-0478.2024.05.008
文献标志码:
A
摘要:
目的 探究Th1/Th2免疫失衡介导的非受体型蛋白酪氨酸激酶2(Janus kinase 2,JAK2)/转录激活因子3(Signal transduction and activator of transcription 3,STAT3)信号通路在慢性偏头痛模型大鼠神经递质释放中的作用及可能机制。方法 根据实验设计将大鼠随机分为对照组、偏头痛组、JAK2抑制(WP1066)组,每组各10只; 试剂盒检测血清Th1/Th2免疫相关因子:干扰素-γ(Interferon-Gamma,IFN-γ)、白细胞介素-4(Interleukin-4,IL-4)、肿瘤坏死因子-α(Tumor necrosis factor-Alpha,TNF-α)、IL-6、TNF-β、IL-2、IL-5、IL-9、IL-10、五羟色胺(5-Hydroxytryptamine,5-HT)、β-内啡肽(Beta-endorphin,β-EP)、γ-氨基丁酸(Gamma-aminobutyric acid,GABA)、一氧化氮(Nitric oxide,NO)水平; 记录各组大鼠挠头次数; 激光多普勒灌注监测仪测量脑血流; Western blotting检测大脑皮质中JAK2,STAT3,磷酸化JAK2(Phospho-JAK2,p-JAK2)及p-STAT3蛋白水平。结果 与对照组比较,偏头痛组血清TNF-α,TNF-β,IFN-γ,IL-2水平明显增高(P<0.05),IL-4,IL-5,IL-9,IL-10水平明显降低(P<0.05),烦躁易动、双耳明显变红、挠头次数增加(P<0.05),脑血流量减少,大脑皮层JAK2,STAT3水平无明显变化(P>0.05),p-JAK2,p-STAT3表达水平增高(P<0.05),血清5-HT、β-EP水平降低,GABA,NO水平增高(P<0.05); 与偏头痛组比较,WP1066组烦躁程度降低,双耳变红程度减弱且挠头次数减少(P<0.05),脑血流量增加,大脑皮层总JAK2、总STAT3表达水平降低,p-JAK2,p-STAT3表达水平降低(P<0.05),血清5-HT,β-EP水平增高,GABA,NO水平降低(P<0.05)。结论 抑制JAK2表达可改善偏头痛模型大鼠行为学表现、改善脑血流量及神经递质水平,这可能与Th1/Th2免疫失衡介导的JAK2/STAT3信号通路有关。
Abstract:
ObjectiveTo explore the role of non-receptor protein tyrosine kinase 2(JAK2)/ signal transduction and activator of transcription 3(STAT3)signaling pathway mediated by Th1/Th2 immune imbalance in neurotransmitter release in chronic migraine rats and its possible mechanism.Methods According to the experimental design, the rats were randomly divided into control group, migraine group and JAK2 inhibition(WP1066)group, with 10 rats in each group. Serum Th1/Th2 immune-related factors were detected by the kit, including interferon-γ(IFN-γ), interleukin-4(IL-4), tumor necrosis factor-α(TNF-α), IL-6, TNF-β, IL-2, IL-5, IL-9, IL-10, serotonin(5-HT), beta-endorphin(beta-EP), gamma-aminobutyric acid(GABA), and nitric oxide(NO)levels. Head scratching times of rats in each group were recorded, cerebral blood flow was measured by laser Doppler perfusion monitor, and protein levels of JAK2, STAT3, phospho-JAK2(p-JAK2)and p-STAT3 in cerebral cortex were detected by Western blotting.Results Compared with the control group, the serum contents of TNF-α, TNF-β, IFN-γ and IL-2 in migraine group were significantly increased(P<0.05), the contents of IL-4, IL-5, IL-9 and IL-10 were significantly decreased(P<0.05), irritability and easy movement, both ears significantly red, head scratching times increased(P<0.05), cerebral blood flow decreased, cerebral cortex JAK2, STAT3 changes were not statistically significant(P>0.05), p-JAK2 and p-STAT3 expression increased(P<0.05), the serum levels of 5-HT and β-EP were decreased, and the levels of GABA and NO were increased(P<0.05). Compared with the migraine group, WP1066 group had less irritability, less redness in both ears and less head scratching(P<0.05), cerebral blood flow increased, total JAK2 and total STAT3 expression decreased, p-JAK2 and p-STAT3 expression decreased(P<0.05), the serum levels of 5-HT and β-EP were increased, and the levels of GABA and NO were decreased(P<0.05).Conclusion Inhibition of JAK2 can improve the behavior, cerebral blood flow and neurotransmitter levels in migraine rats, which may be related to the JAK2/STAT3 signaling pathway mediated by Th1/Th2 immune imbalance.

参考文献/References:

[1] Hovaguimian A,Roth J. Management of chronic migraine[Z], 2022: e067670. [2] Cho S,Chu MK.Serological biomarkers of chronic migraine[J].Curr Pain Headache Rep,2023,27(10):531-542. [3] Martínez-Pías E,García-Azorín D,Trigo-López J,et al.Migraña crónica con cefalea diaria[J].Rev Neurol,2021,72(4):133-140. [4] Faraji F,Shojapour M,Farahani I,et al.Reduced regulatory T lymphocytes in migraine patients[J].Neurol Res,2021,43(8):677-682. [5] Arumugam M.Sugin Lal jabaris S[J].Recent preclinical study offers a promising clue:role of regulatory T cells as biomarkers in migraine.Immunol Lett,2021(240):9-11. [6] Abdi H,Aganj Z,Hosseinzadeh H,et al.Crocin restores the balance of Th1/Th2 immune cell response in ConA-treated human lymphocytes[J].Pharmacol Rep,2022,74(3):513-522. [7] Lv L,Chen Z,Bai W,et al.Taurohyodeoxycholic acid alleviates trinitrobenzene sulfonic acid induced ulcerative colitis via regulating Th1/Th2 and Th17/Treg cells balance[J].Life Sci,2023:121501. [8] Supriya R,Gao Y,Gu Y,et al. Role of exercise intensity on Th1/Th2 immune modulations during the COVID-19 pandemic[Z], 2021: 761382. [9] Lu Y,Ma Q,Yu L,et al. JAK2 inhibitor ameliorates the progression of experimental autoimmune myasthenia gravis and balances Th17/Treg cells via regulating the JAK2/STAT3-AKT/mTOR signaling pathway[Z], 2023: 109693. [10] Nan N,Gong MX,Wang Q,et al. Wuzhuyu decoction relieves hyperalgesia by regulating central and peripheral 5-HT in chronic migraine model rats[Z], 2022: 153905. [11] Wang W,Zhang XY,Bai XY,et al.Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray with episodic and chronic migraine:a proton magnetic resonance spectroscopy study[J].J Headache Pain,2022,23(1):83. [12] Parreira E,Luzeiro I,Pereira Monteiro JM. Enxaqueca crónica e refratária:como diagnosticar e tartar(chronic and refractory migraine: how to diagnose and treat)[J].Acta Med Port,2020,33(11):753-760. [13] Scher AI,Buse DC,Fanning KM,et al.Comorbid pain and migraine chronicity: the chronic migraine epidemiology and outcomes study[J].Neurology,2017,89(5):461-468. [14] Quintana S,Russo M,Manzoni GC,et al.Comparison study between erenumab, fremanezumab, and galcanezumab in the preventive treatment of high frequency episodic migraine and chronic migraine[J].Neurol Sci,2022,43(9):5757-5758. [15] Yuan ZY,Wang W,Zhang XY,et al.Altered functional connectivity of the right caudate nucleus in chronic migraine:a resting-state fMRI study[J].J Headache Pain,2022,23(1):154. [16] Sevivas H,Fresco P.Treatment of resistant chronic migraine with anti-CGRP monoclonal antibodies:a systematic review[J].Eur J Med Res,2022,27(1):86. [17] Anapindi KDB,Yang N,Romanova EV,et al.PACAP and other neuropeptide targets link chronic migraine and opioid-induced hyperalgesia in mouse models[J].Mol Cell Proteomics,2019,18(12):2447-2458. [18] Zhang BB,Zeng MN,Zhang QQ,et al.Ephedrae herba polysaccharides inhibit the inflammation of ovalbumin induced asthma by regulating Th1/Th2 and Th17/Treg cell immune imbalance[J].Mol Immunol,2022,152:14-26. [19] Spagnolo P,Tonelli R,Samarelli AV,et al.The role of immune response in the pathogenesis of idiopathic pulmonary fibrosis:far beyond the Th1/Th2 imbalance[J].Expert Opin Ther Targets,2022,26(7):617-631. [20] Wang W,Sung N,Gilman-Sachs A,et al. Cell profiles in pregnancy and recurrent pregnancy losses:Th1/Th2/Th9/Th17/Th22/Tfh cells[Z], 2020: 2025. [21] 陈菲,陈霞,黄财城.星形胶质细胞外泌体对癫痫大鼠小胶质细胞活化及JAK2/STAT3通路的影响[J].卒中与神经疾病,2022,29(3):267-273, 280. [22] 吴倩.从JAK2/STAT3信号通路研究参芪益智颗粒调控脑星形胶质细胞抗AD作用机制[D].成都:成都中医药大学,2018. [23] 杨建梅,邓海燕,李坤,等.复方藜芍片通过阻断JAK2/STAT3通路抑制皮层神经炎症改善硝酸甘油致大鼠慢性偏头痛[J].世界科学技术-中医药现代化,2018,20(12):2224-2230.

备注/Memo

备注/Memo:
基金项目:2024年度中医药类科学研究课题计划项目(2024198)
更新日期/Last Update: 2024-10-20