Mechanism of JAK2/STAT3 signaling pathway mediated by Th1/Th2 immune imbalance in neurotransmitter release in chronic migraine model rats
黄娜 1李静 1祁天培 2柴琳洁 3李琳3
扫码查看
点击上方二维码区域，可以放大扫码查看
作者信息
1. 073000 河北省定州市人民医院中医科
2. 廊坊市卫生急救中心直属急救站
3. 石家庄市藁城人民医院
折叠
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-y(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、五轻色胺(5-Hydroxy tryptamine,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
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 imbal-ance 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 inhibi-tion(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(GA-BA),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 in-creased(P＜0.05),the contents of IL-4,IL-5,IL-9 and IL-10 were significantly decreased(P＜0.05),irri-tability 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 in-creased,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.
维普
万方数据