Thromboxane A2 receptor antagonist SQ29548 reduces ischemic stroke-induced microglia/macrophages activation and enrichment, and ameliorates brain injury.
Thromboxane A2 receptor antagonist SQ29548 reduces ischemic stroke-induced microglia/macrophages activation and enrichment, and ameliorates brain injury.
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血栓素 A2 受体拮抗剂 SQ29548 减少缺血性中风诱导的小胶质细胞/巨噬细胞活化和富集，并改善脑损伤
DOI：
10.1038/srep35885
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发表时间：
2016-10-24
影响因子：
4.6
通讯作者：
Xia W
中科院分区：
文献类型：
--
作者：
Yan A;Zhang T;Yang X;Shao J;Fu N;Shen F;Fu Y;Xia W
血栓素A2受体（TXA 2 R）的激活被认为参与血栓形成/止血和炎症反应。我们先前已经表明，TXA 2 R拮抗剂SQ 29548通过抑制ERK通路来减弱BV 2小胶质细胞的活化，但其作用尚未在体内进行测试。本研究旨在探讨血栓素A2受体（TXA 2 R）在小鼠脑缺血再灌注损伤后小胶质细胞/巨噬细胞活化中的作用。成年雄性ICR小鼠经历90分钟短暂大脑中动脉闭塞（tMCAO）。再灌注后即刻和24 h，同侧脑室注射SQ 29548，每次10 μl，2.6 μmol/ml。分别采用甲酚紫法、定量聚合酶链反应（qPCR）和免疫荧光双染色法测定脑梗死体积、炎性细胞因子释放和小胶质细胞/巨噬细胞活化。缺血再灌注后，TXA 2 R在同侧脑组织中的表达显著增加，并与梗死区活化的小胶质细胞/巨噬细胞共定位。给予SQ 29548可抑制小胶质细胞/巨噬细胞的活化和富集，包括M1和M2表型，并减弱缺血诱导的IL-1 β、IL-6和TNF-α上调以及iNOS释放。TXA 2 R拮抗剂SQ 29548可抑制缺血诱导的炎症反应，并进一步减少小胶质细胞/巨噬细胞活化和缺血/再灌注脑损伤。
Thromboxane A2 receptor (TXA2R) activation is thought to be involved in thrombosis/hemostasis and inflammation responses. We have previously shown that TXA2R antagonist SQ29548 attenuates BV2 microglia activation by suppression of ERK pathway, but its effect is not tested in vivo. The present study aims to explore the role of TXA2R on microglia/macrophages activation after ischemia/reperfusion brain injury in mice. Adult male ICR mice underwent 90-min transient middle cerebral artery occlusion (tMCAO). Immediately and 24 h after reperfusion, SQ29548 was administered twice to the ipsilateral ventricle (10 μl, 2.6 μmol/ml, per dose). Cerebral infarction volume, inflammatory cytokines release and microglia/macrophages activation were measured using the cresyl violet method, quantitative polymerase chain reaction (qPCR), and immunofluorescence double staining, respectively. Expression of TXA2R was significantly increased in the ipsilateral brain tissue after ischemia/reperfusion, which was also found to co-localize with activated microglia/macrophages in the infarct area. Administration of SQ29548 inhibited microglia/macrophages activation and enrichment, including both M1 and M2 phenotypes, and attenuated ischemia-induced IL-1ß, IL-6, and TNF-α up-regulation and iNOS release. TXA2R antagonist SQ29548 inhibited ischemia-induced inflammatory response and furthermore reduced microglia/macrophages activation and ischemic/reperfusion brain injury.
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影响因子：
3.7
作者：
Sobolesky PM;Halushka PV;Garrett-Mayer E;Smith MT;Moussa O
通讯作者：
Moussa O
DOI：
10.3791/50326
发表时间：
2013-05-12
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
DeVos SL;Miller TM
通讯作者：
Miller TM
影响因子：
15.9
作者：
Kreutzberg, GW
通讯作者：
Kreutzberg, GW
Malibatol A 以 PPARgamma 依赖性方式调节实验性中风中小胶质细胞 M1/M2 极化
影响因子：
9.3
作者：
Pan J;Jin JL;Ge HM;Yin KL;Chen X;Han LJ;Chen Y;Qian L;Li XX;Xu Y
通讯作者：
Xu Y
影响因子：
6.3
作者：
Gelosa, Paolo;Lecca, Davide;Sironi, Luigi
通讯作者：
Sironi, Luigi