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

Autor: Lihui Men, Wenting Hui, Tongtong Song, Xia Chen, Xi Wang, Wen-Jing Du, Yi-Wen Gu, Siwei Zhang
Rok vydání: 2022
Předmět:
Zdroj: Chinese Journal of Analytical Chemistry. 50:39-46
ISSN: 1872-2040
DOI: 10.1016/j.cjac.2021.08.002
Popis: Focal cerebral ischemia is a major cardiovascular disease that seriously threatens human health. Its neuromodulator is sodium butyrate, whose underlying mechanisms remain unclear. This study aimed to clarify the neuronal anti-inflammatory mechanisms of sodium butyrate against focal cerebral ischemia. A rat model of focal cerebral ischemia was established by administering sodium butyrate before middle cerebral artery occlusion (MCAO) was conducted. The neuroprotective effects of sodium butyrate were evaluated 24 h after MCAO in terms of neurological score, infarction volume, and inflammatory biomarkers. The expression levels 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. HT22 cells stimulated with oxygen and glucose deprivation (OGD) were treated with sodium butyrate and siNur77 to explore the role of sodium butyrate in the Nur77/NLRP3-mediated inflammatory response. Sodium butyrate treatment significantly attenuated the neurological impairment and neuroinflammation induced by cerebral ischemia. In cerebral ischemia, Nur77 expression was dysregulated as mediated by sodium butyrate, and NLRP3-related inflammatory factors were produced in vivo and in vitro. Nur77 was identified as a negative regulator of NLRP3 in HT22 cells under OGD conditions. The anti-inflammatory effect of sodium butyrate was achieved by upregulating the expression of Nur77, which subsequently suppressed the neuronal NLRP3-mediated inflammatory response. Overall, sodium butyrate elicited a neuroprotective effect against focal cerebral ischemia by modulating Nur77/NLRP3-mediated inflammatory responses.
Databáze: OpenAIRE
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