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Sodium butyrate protects against focal cerebral ischemic injury through regulation of the nuclear receptor Nur77

分析化学 2021年

作者： MEN Li-Hui SONG Tong-Tong WANG Xi HUI Wen-Ting GU Yi-Wen DU Wen-Jing ZHANG Si-Wei CHEN Xia Department of Pharmacology， College of Basic Medical Sciences， Jilin University

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.

关键词： Sodium butyrate Focal cerebral ischemia nuclear receptor subfamily 4 group a1 Nod-like receptor protein 3 Inflammatory response

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