Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice
Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice
复制标题
Dectin-1/Syk 信号传导在小鼠缺血性中风后触发神经炎症。
DOI：
10.1186/s12974-019-1693-z
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发表时间：
2020-01-11
影响因子：
9.3
通讯作者：
Cui, Gui-Yun
中科院分区：
文献类型：
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作者：
Ye, Xin-Chun;Hao, Qi;Cui, Gui-Yun
研究背景树突状细胞相关C型凝集素-1（Dectin-1）受体参与阿尔茨海默病和创伤性脑损伤的神经炎症反应。本研究旨在使用局灶性皮质缺血性中风模型探讨Dectin-1及其下游靶点脾脏酪氨酸激酶（Syk）在缺血性中风后早期脑损伤中的作用。方法采用成年雄性C57 BL/6 J小鼠建立缺血性脑卒中模型。在缺血性卒中后第1、3、5和7天进行神经功能评分、粘合剂清除试验和足部错误试验。通过蛋白质印迹法分析缺血性卒中后缺血性脑组织和体外氧-葡萄糖剥夺/复氧（OGD/R）损伤的BV 2小胶质细胞中Dectin-1、Syk、磷酸化（p）-Syk、肿瘤坏死因子-α（TNF-α）和诱导型一氧化氮合酶（iNOS）的表达。分别用尼氏染色和免疫荧光染色评价脑梗死体积和Iba 1阳性细胞。Dectin-1拮抗剂海带多糖（LAM）和Syk磷酸化的选择性抑制剂（piceatannol; PIC）用于干预。结果缺血性脑卒中后3、5、7 d，Dectin-1、Syk和p-Syk表达均显著增强，3 d达高峰。Dectin-1拮抗剂LAM或Syk抑制剂PIC可减少缺血性卒中后第3天Iba 1阳性细胞数和TNF-α和iNOS表达，减少脑梗死体积，并改善神经功能。此外，体外数据显示，在BV 2小胶质细胞中，在3小时OGD和0、3和6小时再灌注后，Dectin-1、Syk和p-Syk表达增加。LAM和PIC也降低了OGD/R诱导后3 h TNF-α和iNOS的表达。结论Dectin-1/Syk信号通路在缺血性脑卒中后炎症反应中起重要作用，对Dectin-1/Syk信号通路在脑卒中中的作用有待进一步研究。
Background Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer's disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model. Methods Adult male C57BL/6 J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test, and foot-fault test were evaluated on days 1, 3, 5, and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl's and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention. Results Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5, and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-alpha and iNOS expression, decreased the brain infarct volume, and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk, and p-Syk expression was increased following the 3-h OGD and 0, 3, and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-alpha and iNOS expression 3 h after OGD/R induction. Conclusion Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted.