MitoQ attenuates brain damage by polarizing microglia towards the M2 phenotype through inhibition of the NLRP3 inflammasome after ICH
MitoQ attenuates brain damage by polarizing microglia towards the M2 phenotype through inhibition of the NLRP3 inflammasome after ICH
复制标题
MitoQ 通过抑制 ICH 后的 NLRP3 炎症小体，将小胶质细胞极化为 M2 表型，从而减轻脑损伤。
DOI：
10.1016/j.phrs.2020.105122
复制
发表时间：
2020-11-01
影响因子：
9.3
通讯作者：
Feng, Hua
中科院分区：
文献类型：
--
作者：
Chen, Weixiang;Guo, Chao;Feng, Hua
小胶质细胞表型在脑出血（ICH）后继发性损伤中起重要作用，M1小胶质细胞促进炎症损伤，M2小胶质细胞抑制神经炎症，促进血肿吸收。然而，对于脑出血后小胶质细胞的表型转化，目前尚无有效的干预措施。本研究旨在阐明选择性线粒体ROS抗氧化剂MitoQ对小胶质细胞Ml态极化和继发性脑损伤的保护作用。体内数据显示，MitoQ减轻脑出血后的神经功能缺损，减少炎症、水肿和血肿体积。此外，MitoQ在ICH后体内和体外均降低了M1标记物的表达，增加了M2标记物的表达。在机制上，MitoQ阻断了FeCl2处理的小胶质细胞中线粒体ROS的过量产生和NLRP3炎性体的激活。此外，NLRP3 siRNA将fecl2处理的小胶质细胞从Ml细胞转移到M2细胞，表明mitoq诱导的极化状态可能是由线粒体ROS/NLRP-3途径介导的。综上所述，MitoQ减轻了脑出血后继发性脑损伤，并通过将小胶质细胞向M2表型转移来加速血肿消退。
Microglial phenotype plays an important role in secondary injury after intracerebral haemorrhage (ICH), with M1 microglia promoting inflammatory injury and M2 microglia inhibiting neuroinflammation and promoting haematoma absorption. However, there is no effective intervention for regulating the phenotypic transformation of microglia after ICH. This study aimed to elucidate the protective effect of MitoQ, a selective mitochondrial ROS antioxidant, against microglial Ml state polarization and secondary brain injury. The in vivo data showed that MitoQ attenuated neurological deficits and decreased inflammation, oedema and haematoma volume after ICH. In addition, MitoQ decreased the expression of M1 markers and increased the expression of M2 markers both in vivo and in vitro after ICH. Mechanistically, MitoQ blocked overproduction of mitochondrial ROS and activation of the NLRP3 inflammasome in FeCl2 -treated microglia. Moreover, NLRP3 siRNA shifted FeCl2-treated microglia from the Ml to the M2 cells, revealing that MitoQ-induce polarization states may be mediated by the mitochondrial ROS/NLRP-3 pathway. In summary, MitoQ alleviates secondary brain injury and accelerates haematoma resolution by shifting microglia towards the M2 phenotype after ICH.