Peng Xiao-Yun, Yuan Bo, Li Xing-Lan, Bao Ying-Cun, Luo Wen-Jun, Zhang Yan-Ju, Zhao Min, Wang Jin-Hai
Department of Rehabilitation Medicine, The Second Hospital of Lanzhou University, Lanzhou 730030, China.
Clinical Center of Acupuncture and Moxibustion, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou 730000.
Zhen Ci Yan Jiu. 2023 Sep 25;48(9):852-9. doi: 10.13702/j.1000-0607.20220842.
To explore the molecular mechanism of electrical stimulation with scalp acupuncture (ESA) in alleviating neuroinflammatory injury in ischemic stroke rats based on interferon γ (IFN-γ)-mediated Janus kinase/signal transduction and transcriptional activator 1 (JAK/STAT1) signaling pathway.
Fifty-six SD rats aged 7 weeks were randomly divided into normal, model, ESA and inhibitor groups, with 14 rats in each group. The middle cerebral artery embolization rat model was established by means of thread embolization. Rats in the inhibitor group were intraperitoneally injected with the inhibitor PJ34 (5 mg/mL, 25 mg/kg) once a day for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. The percentage of cerebral infarction volume was detected by TTC staining. The positive expressions of interleukin (IL)-6 and IL-10 in cerebral cortex were detected by immunohistochemistry. The protein expression levels of IFN-γ, JAK1, JAK2 and phosphorylated (p)-STAT1 in rats cerebral cortex were detected by Western blot.
Compared with the normal group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were increased (<0.01), while the expression level of IL-10 was decreased (<0.01) in the model group. Compared with the model group, the neurological deficit score and neurobehavioral score after treatment were significantly decreased (<0.01), the percentage of cerebral infarction volume was decreased (<0.01), the expression levels of IL-6, IFN-γ, JAK1, JAK2 and p-STAT1 in cerebral cortex were decreased (<0.01), while the expression level of IL-10 was increased (<0.01) in the ESA and inhibitor groups. ESA was superior to inhibitors in improving neurological deficit score and down-regulating p-STAT1 expression (<0.05, <0.01), and was inferior to inhibitor in reducing the percentage of cerebral infarction volume as well as down-regulating IFN-γ and JAK1 (<0.01, <0.05).
Down-regulating the expression of IFN-γ and inhibiting the activity of JAK/STAT1 signaling pathway may be one of the mechanisms by which ESA alleviates neuroinflammatory injury in ischemic stroke rats.
基于干扰素γ（IFN-γ）介导的Janus激酶/信号转导及转录激活因子1（JAK/STAT1）信号通路，探讨头针电刺激（ESA）减轻缺血性脑卒中大鼠神经炎性损伤的分子机制。
将56只7周龄的SD大鼠随机分为正常组、模型组、ESA组和抑制剂组，每组14只。采用线栓法建立大脑中动脉栓塞大鼠模型。抑制剂组大鼠每天腹腔注射抑制剂PJ34（5mg/mL，25mg/kg），连续7天。ESA组大鼠采用ESA（2Hz/100Hz，1mA）刺激双侧前顶颞斜线（MS6），每天30分钟，连续7天。干预前后分别评估神经功能缺损评分和神经行为学评分。通过TTC染色检测脑梗死体积百分比。采用免疫组织化学法检测大脑皮质中白细胞介素（IL）-6和IL-10的阳性表达。采用蛋白质免疫印迹法检测大鼠大脑皮质中IFN-γ、JAK1、JAK2和磷酸化（p）-STAT1的蛋白表达水平。
与正常组相比，模型组神经功能缺损评分、神经行为学评分、脑梗死体积百分比、大脑皮质中IL-6、IFN-γ、JAK1、JAK2和p-STAT1的表达水平均升高（<0.01），而IL-10表达水平降低（<0.01）。与模型组相比，ESA组和抑制剂组治疗后神经功能缺损评分和神经行为学评分显著降低（<0.01），脑梗死体积百分比降低（<0.01），大脑皮质中IL-6、IFN-γ、JAK1、JAK2和p-STAT1的表达水平降低（<0.01），而IL-10表达水平升高（<0.01）。ESA在改善神经功能缺损评分和下调p-STAT1表达方面优于抑制剂（<0.05，<0.01），在降低脑梗死体积百分比以及下调IFN-γ和JAK1方面不如抑制剂（<0.01，<0.05）。
下调IFN-γ表达并抑制JAK/STAT1信号通路活性可能是ESA减轻缺血性脑卒中大鼠神经炎性损伤的机制之一。
