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丁酸钠可改善高脂饮食喂养小鼠的神经毒性并发挥抗炎作用。

Sodium butyrate ameliorates neurotoxicity and exerts anti-inflammatory effects in high fat diet-fed mice.

机构信息

Department of Applied Life Science, Graduate School of Konkuk University, Chungju, 27478, South Korea.

BK21 FOUR, GLOCAL Education Program for Nutraceutical and Biopharmaceutical Research, Konkuk University, Chungju, 27478, South Korea.

出版信息

Food Chem Toxicol. 2022 Jan;159:112743. doi: 10.1016/j.fct.2021.112743. Epub 2021 Dec 8.

DOI:10.1016/j.fct.2021.112743
PMID:34890760
Abstract

The prevalence of high-fat diet consumption-related disorders is increasing, and it is often associated with oxidative stress, inflammation, and dysregulation in the brain may lead to neurodegenerative diseases (NDDs). Our study aims to evaluate the neuroprotective effects of sodium butyrate (NaB) on HFD-fed mice. In this study, four-week-old male C57Bl/6NTac mice were divided into three groups; the control group, the HFD group, and the HFD + NaB group where mice received 11 mg/kg body weight of NaB with HFD. Western blotting, reverse transcription-PCR, and ELISA were used for biochemical analysis of brain specimens. We found that NaB restored bodyweight and attenuated P-53, Bcl-2-associated X protein (BAX), and caspase cascades in the brains of HFD-fed mice. In addition. NaB reduced the expressions of proinflammatory cytokines and positively modulated antioxidant biomarkers. NaB treatment upregulated the expression of the growth factor-related factors PPARγ, CREB, and BDNF in the brain tissues of HFD-fed mice. Furthermore, we found that NaB significantly ameliorated glucocorticoid receptor and NLRP3 inflammasome expression. Based on our findings, NaB suppressed apoptotic and inflammatory cytokines and enhanced the expression of endogenous antioxidants in brain tissues of HFD-fed mice. Our data strongly suggests that NaB could be utilized as an effective therapeutic agent for NDDs.

摘要

高脂肪饮食相关疾病的患病率正在上升,而其常与氧化应激、炎症和大脑失调有关,这些可能会导致神经退行性疾病(NDDs)。我们的研究旨在评估丁酸钠(NaB)对高脂肪饮食喂养的小鼠的神经保护作用。在这项研究中,将 4 周龄雄性 C57Bl/6NTac 小鼠分为三组:对照组、高脂肪饮食组和高脂肪饮食+NaB 组,其中高脂肪饮食+NaB 组的小鼠接受 11mg/kg 体重的 NaB。采用 Western blot、逆转录-PCR 和 ELISA 对脑组织进行生化分析。我们发现,NaB 恢复了体重,并减弱了高脂肪饮食喂养小鼠大脑中的 P-53、Bcl-2 相关 X 蛋白(BAX)和半胱天冬酶级联反应。此外,NaB 降低了促炎细胞因子的表达,并正向调节了抗氧化生物标志物。NaB 处理上调了高脂肪饮食喂养小鼠脑组织中生长因子相关因子 PPARγ、CREB 和 BDNF 的表达。此外,我们发现 NaB 显著改善了糖皮质激素受体和 NLRP3 炎性小体的表达。基于我们的发现,NaB 抑制了凋亡和促炎细胞因子的表达,并增强了高脂肪饮食喂养小鼠脑组织中内源性抗氧化剂的表达。我们的数据强烈表明,NaB 可作为治疗 NDDs 的有效治疗剂。

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