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Astragaloside Ⅳ suppresses post-ischemic natural killer cell infiltration and activation in the brain:involvement of histone deacetylase inhibition

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Frontiers of Medicine 2021年第1期15卷 79-90页

作者： baokai dou Shichun Li Luyao Wei Lixin Wang Shiguo Zhu Zhengtao Wang Zunji Ke Kaixian Chen Zhifei Wang School of Basic Medical Sciences Shanghai University of Traditional Chinese MedicineShanghai 201203China Institute of Chinese Materia Medica Shanghai University of Traditional Chinese MedicineShanghai 201203China Academy of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghai 201203China

Natural killer(NK)cells,a type of cytotoxic lymphocytes,can infiltrate into ischemic brain and exacerbate neuronal cell *** Ⅳ(ASIV)is the major bioactive ingredient of Astragalus membranaceus,a Chinese herbal medicine,and possesses potent immunomodulatory and neuroprotective *** study investigated the effects of ASIV on post-ischemic brain infiltration and activation of NK *** reduced brain infarction and alleviated functional deficits in MCAO rats,and these beneficial effects persisted for at least 7 *** NK cells infiltrated into the ischemic hemisphere on day 1 after brain ischemia,and this infiltration was suppressed by ***,ASIV reversed NK cell deficiency in the spleen and blood after brain *** inhibited astrocyte-derived CCL2 upregulation and reduced CCR2+NK cell levels in the ischemic ***,ASIV attenuated NK cell activating receptor NKG2D levels and reduced interferon-γ*** restored acetylation of histone H3 and the p65 subunit of nuclear factor-κB in the ischemic brain,suggesting inhibition of histone deacetylase(HDAC).Simultaneously,ASIV prevented p65 nuclear *** effects of ASIV on reducing CCL2 production,restoring acetylated p65 levels and preventing p65 nuclear translocation were mimicked by valproate,an HDAC inhibitor,in astrocytes subjected to oxygen-glucose *** findings suggest that ASIV inhibits post-ischemic NK cell brain infiltration and activation and reverses NK cell deficiency in the periphery,which together contribute to the beneficial effects of ASIV against brain ***,ASIV’s effects on suppressing NK cell brain infiltration and activation may involve HDAC inhibition.

关键词： astragalosideⅣ brain ischemia natural killer cells histone deacetylase nuclear factor-κB

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