期刊
INFLAMMATION RESEARCH
卷 71, 期 1, 页码 93-106出版社
SPRINGER BASEL AG
DOI: 10.1007/s00011-021-01515-5
关键词
Cerebral ischemic injury; Dexmedetomidine; Nrf2; HO-1; NLRP3; Microglia polarization; Oxidative stress; Inflammatory injury
资金
- Research Foundation of the Second Affiliated Hospital of Harbin Medical University [KYBS2015-02]
- Postdoctoral Research Fund of Heilongjiang Province [LBH-Z15139]
- Heilongjiang Health and Family Planning Commission Research Project [2017-078]
Dex promotes M2 polarization of microglia, attenuates oxidative stress and inflammation, and protects against cerebral ischemic injury by activating the Nrf2/HO-1 pathway and inhibiting NLRP3 inflammasome.
Introduction Cerebral ischemic injury is associated with long-term disability. Dexmedetomidine (Dex) can exert neuroprotective effects on cerebral ischemic/reperfusion injury. The present study explored the mechanism of Dex in cerebral ischemic injury. Materials and methods To this end, the permanent middle cerebral artery occlusion (p-MCAO) mouse model was established and treated with Dex or/and Nrf2 inhibitor ML385. Subsequently, microglia were subjected to oxygen-glucose deprivation (OGD) in sugar-free environment and thereafter treated with Dex, Nrf2 inhibitor, and NLRP3 lentiviral overexpression vector, respectively. Results Dex alleviated the neurobehavioral deficit of p-MCAO mice, reduced brain water content, relieved pathological changes, and reduced cerebral infarction size. Dex promoted the polarization of microglia from M1 to M2, thus ameliorating oxidative stress and inflammatory responses. Our results showed that Dex promoted M2-polarization of microglia in vivo and in vitro by promoting HO-1 expression via Nrf2 nuclear import. Moreover, the Nrf2/HO-1 axis inhibited the activation of NLRP2 inflammasome and NLRP3 overexpression reversed the effect of Dex. Conclusion In conclusion, Dex promoted M2-polarization of microglia and attenuated oxidative stress and inflammation, and thus protected against cerebral ischemic injury by activating the Nrf2/HO-1 pathway and inhibiting NLRP3 inflammasome.
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