JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke
JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke
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JNK-IN-8 是一种 c-Jun N 末端激酶抑制剂，通过抑制缺血性中风的神经炎症来改善功能恢复
DOI：
10.1002/jcp.29183
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发表时间：
2020
影响因子：
5.6
通讯作者：
Geng Wujun
中科院分区：
文献类型：
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作者：
Zheng Jianjian;Dai Qinxue;Han Kunyuan;Hong W;ong;Jia Danyun;Mo Yunchang;Lv Ya;Tang Hongli;Fu Hongxing;Geng Wujun
JNK是一种重要的丝裂原活化蛋白激酶（mitogen activated protein kinase，MAPK），在缺血性脑损伤中被激活，在脑缺血性损伤中起着至关重要的作用。新近研究表明，JNK‐IN‐8（一种高度特异性的JNK抑制剂）通过控制神经元凋亡和炎症来调节创伤性脑损伤。然而，JNK-IN-8在缺血性卒中中的功能以及JNK-IN-8关于神经保护的潜在机制尚不清楚。在这项工作中，雄性大鼠在短暂性大脑中动脉闭塞后接受JNK-IN-8治疗，然后评估改良的神经功能评分（mNSS）、足错试验（FFT）、白细胞介素-1 β（IL-1β）、IL-6和肿瘤坏死因子-α（TNF-α）水平。我们发现，JNK-IN-8治疗的MCAO大鼠在空间学习方面表现出可观察到的改善，如通过改进的mNSS测试的，并且显示出通过FFT测量的感觉运动功能恢复。JNK-IN-8还通过减少小胶质细胞活化和减少IL-6、IL-1β和TNF-α表达发挥抗炎作用。此外，JNK-IN-8抑制JNK和核因子-κB（NF-κB）信号传导的活化，如磷酸化-JNK和p65水平降低所示。所有数据表明，JNK-IN-8通过抑制JNK/NF-κB抑制神经炎症并改善神经功能，是预防缺血性脑损伤的有前景的药物。
C‐Jun N‐terminal kinase (JNK) is a pivotal MAPK (mitogen‐activated protein kinase), which activated by ischemia brain injury and plays a fairly crucial function in cerebral ischemic injury. Emerging studies demonstrated that JNK‐IN‐8 (a JNK inhibitor with high specificity) regulates traumatic brain injury through controlling neuronal apoptosis and inflammation. However, the function of JNK‐IN‐8 in ischemic stroke and the mechanisms underlying of JNK‐IN‐8 about neuroprotection are not well understood. In this work, male rats were treated with JNK‐IN‐8 after transient middle cerebral artery occlusion, and then the modified improved neurological function score (mNSS), the foot‐fault test (FFT), interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) levels were assessed. We found that JNK‐IN‐8‐treated rats with MCAO exerted an observable melioration in space learning as tested by the improved mNSS, and showed sensorimotor functional recovery as measured by the FFT. JNK‐IN‐8 also played anti‐inflammatory roles as indicated through decreased activation of microglia and decreased IL‐6, IL‐1β, and TNF‐α expression. Furthermore, JNK‐IN‐8 suppressed the activation of JNK and nuclear factor‐κB (NF‐κB) signaling as indicated by the decreased level of phosphorylated‐JNK and p65. All data demonstrate that JNK‐IN‐8 inhibits neuroinflammation and improved neurological function by inhibiting JNK/NF‐κB and is a promising agent for the prevention of ischemic brain injury.