槲皮素通过抑制小胶质细胞源性氧化应激和 TLR4 介导的炎症反应缓解新生鼠缺氧缺血性脑损伤。
Quercetin alleviates neonatal hypoxic-ischemic brain injury by inhibiting microglia-derived oxidative stress and TLR4-mediated inflammation.
机构信息
Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China.
Department of Anesthesia, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China.
出版信息
Inflamm Res. 2020 Dec;69(12):1201-1213. doi: 10.1007/s00011-020-01402-5. Epub 2020 Sep 18.
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.
目的和设计
用氧葡萄糖剥夺（OGD）刺激小胶质细胞，用槲皮素进行处理，以研究其对氧化应激和炎症反应的影响，并探讨是否涉及 Toll 样受体 4（TLR4）信号通路。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。
材料和对象
使用小鼠 BV2 小胶质细胞和出生后第 7 天的新生小鼠。
处理
在细胞实验中使用预定浓度的槲皮素。在 HI 损伤后，通过腹腔注射（i.p.）给予槲皮素（50mg/kg），注射时间点为：0、24 和 48 小时。
方法
细胞活力测定、Western blot、qRT-PCR、ELISA、HIBI 模型构建和行为测试。
结果
本研究首先表明，槲皮素可保护 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，槲皮素抑制了 OGD 诱导的 BV2 细胞中炎症因子的表达，并抑制了 TLR4/MyD88/NF-κB 信号通路。最后，揭示了槲皮素可有效减轻 HIBI 小鼠的脑梗死体积和认知及运动功能缺陷。
结论
这些结果表明，槲皮素在 HIBI 小鼠中的神经保护作用部分归因于抑制激活的小胶质细胞中的氧化应激和 TLR4 介导的炎症反应。
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