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。
Objective To 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-γand 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 andβ-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 andβ-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 J
作者
黄娜
李静
祁天培
柴琳洁
李琳
Huang Na;Li Jing;Qi Tianpei(Department of Traditional Chinese Medicine,Dingzhou People's Hospital,Dingzhou Hebei 073000;不详)
出处
《卒中与神经疾病》
2024年第5期465-469,共5页
Stroke and Nervous Diseases
基金
2024年度中医药类科学研究课题计划项目(2024198)。
