Sodium butyrate protects against focal cerebral ischemic injury through regulation of the nuclear receptor Nur77
作者机构：Department of Pharmacology， College of Basic Medical Sciences， Jilin University
出 版 物：《分析化学》 (Chinese Journal of Analytical Chemistry)
年 卷 期：2021年
核心收录：
学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
基 金：supported by the Jilin Province Development and Reform Commission (grant number 2016C023)
主 题：Sodium butyrate Focal cerebral ischemia Nuclear receptor subfamily 4 group A1 Nod-like receptor protein 3 Inflammatory response
摘 要：Focal cerebral ischemia is a major cardiovascular disease that seriously threatens human health. Sodium butyrate has been identified as a neuromodulator in cerebral ischemia but the underlying mechanisms remain unclear. The present study aimed to clarify the neuronal anti-inflammatory mechanisms of sodium butyrate against focal cerebral ischemia. A focal cerebral ischemic rat model was established by administering sodium butyrate prior to middle cerebral artery occlusion (MCAO). The neuroprotective effects of sodium butyrate were evaluated 24 h after MCAO， using neurological score， infarction volume， and inflammatory biomarkers as the criteria. The expressions of nuclear receptor subfamily 4 group A1 (Nur77)， nod-like receptor protein 3 (NLRP3)， caspase-1 and interleukin-1β (IL-1β) in brain tissues were also analyzed. To explore the role of sodium butyrate in Nur77/NLRP3-mediated inflammatory response， oxygen and glucose deprivation (OGD)-stimulated HT22 cells were treated with sodium butyrate and siNur77. Sodium butyrate treatment significantly attenuated neurological impairment and neuroinflammation induced by cerebral ischemia. Sodium butyrate-mediated dysregulation of Nur77 expression and production of NLRP3-related inflammatory factors were observed in cerebral ischemia in vivo and in vitro. In addition， Nur77 was identified as a negative regulator of NLRP3 in HT22 cells under OGD. The results indicate that the anti-inflammatory effect of sodium butyrate was achieved by upregulating Nur77 expression， which subsequently suppressed neuronal NLRP3-mediated inflammatory response. Overall， sodium butyrate clearly has a neuroprotective effect against focal cerebral ischemia by modulating Nur77/NLRP3-mediated inflammatory response.
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