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Quercetin alleviates neonatal hypoxic-ischemic brain injury by inhibiting microglia-derived oxidative stress and TLR4-mediated inflammation.
Inflammation Research ( IF 6.7 ) Pub Date : 2020-09-18 , DOI: 10.1007/s00011-020-01402-5
Kai Le 1 , Zhiping Song 2 , Jie Deng 3 , Xin Peng 4 , Jun Zhang 1 , Liang Wang 1 , Lu Zhou 1 , Haidi Bi 1 , Zhengyu Liao 5 , Zhen Feng 1
Affiliation  

Objective and design

Microglia stimulated by oxygen glucose deprivation (OGD) were treated with quercetin to investigate the effect on oxidative stress and the inflammatory response and to explore whether toll-like receptor 4 (TLR4) signaling was involved. In addition, the effect of quercetin on the neurological functions of neonatal mice with hypoxic-ischemic brain injury (HIBI) was examined.

Materials and subjects

Mouse BV2 microglial cells and postnatal day 7 neonatal mice were used.

Treatment

A predetermined concentration of quercetin was used in cell experiments. Quercetin was injected i.p. (50 mg/kg) at three time points after HI insult: 0, 24, and 48 h.

Methods

Cell viability assay, Western blotting, qRT-RCR, ELISA, HIBI model construction and behavioral tests.

Results

This study first showed that quercetin protected BV2 cells from OGD-induced damage and reversed the changes in microglial oxidative stress-related molecules. Second, quercetin inhibited OGD-induced expression of inflammatory factors in BV2 cells and suppressed TLR4/MyD88/NF-κB signaling. Finally, quercetin was disclosed to be effective in mitigating cerebral infarct volume and cognitive and motor function deficits in HIBI mice.

Conclusion

These results suggest that the neuroprotective effect of quercetin in HIBI mice is partially due to the inhibition of oxidative stress and TLR4-mediated inflammatory responses in activated microglia.



中文翻译:

槲皮素通过抑制小胶质细胞衍生的氧化应激和 TLR4 介导的炎症来减轻新生儿缺氧缺血性脑损伤。

目标与设计

用槲皮素处理氧葡萄糖剥夺 (OGD) 刺激的小胶质细胞,以研究对氧化应激和炎症反应的影响,并探索是否涉及 toll 样受体 4 (TLR4) 信号传导。此外,还研究了槲皮素对缺氧缺血性脑损伤 (HIBI) 新生小鼠神经功能的影响。

材料和科目

使用小鼠 BV2 小胶质细胞和出生后第 7 天的新生小鼠。

治疗

在细胞实验中使用预定浓度的槲皮素。在 HI 损伤后的三个时间点腹腔注射槲皮素 (50 mg/kg):0、24 和 48 小时。

方法

细胞活力测定、蛋白质印迹、qRT-RCR、ELISA、HIBI 模型构建和行为测试。

结果

该研究首先表明,槲皮素保护 BV2 细胞免受 OGD 诱导的损伤,并逆转小胶质细胞氧化应激相关分子的变化。其次,槲皮素抑制 OGD 诱导的 BV2 细胞中炎症因子的表达,并抑制 TLR4/MyD88/NF-κB 信号传导。最后,发现槲皮素可有效减轻 HIBI 小鼠的脑梗塞体积以及认知和运动功能缺陷。

结论

这些结果表明,槲皮素对 HIBI 小鼠的神经保护作用部分是由于抑制了活化小胶质细胞中的氧化应激和 TLR4 介导的炎症反应。

更新日期:2020-09-20
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