七氟醚调控 NRF2 / HO-1 / HMGB1 通路减轻缺氧诱导的小胶质细胞炎症反应
作者:
作者单位:

1.甘肃省定西市人民医院麻醉科,甘肃 定西 743000;2.甘肃省定西市人民医院泌尿外科,甘肃 定西 743000; 3.湖南省娄底市中心医院,湖南 娄底 417000

中图分类号:

R-33


Sevoflurane regulates the NRF2 / HO-1/ HMGB1 pathway and reduces hypoxia-induced inflammatory responses in microglia
Author:
Affiliation:

1.Department of Anesthesiology, Dingxi People’s Hospital of Gansu Province, Dingxi 743000, China. 2. Department of Urology, Dingxi People’s Hospital of Gansu Province, Dingxi 743000. 3. Loudi Central Hospital of Hunan Province, Loudi 417000

  • 摘要
  • | |
  • 访问统计
  • |
  • 参考文献
  • | |
  • 引证文献
  • | |
  • 文章评论
    摘要:

    目的 探讨七氟醚对缺氧诱导的小胶质细胞炎症反应的影响,及对转录因子 NF-E2 相关因子 2 (NRF2)及血红素加氧酶 1(HO-1) / 高迁移率族蛋白 B1(HMGB1)通路的调控作用。 方法 缺氧不同时间(0、2、4、 6、8、12 h)诱导 BV-2 小胶质细胞活化建立炎症模型,倒置显微镜观察细胞活化形态并计算活化细胞比例;Western blot 法检测小胶质细胞 NRF2、HO-1、HMGB1 及白介素 1β(IL-1β)蛋白表达水平,筛选最佳缺氧时间 8 h。 观察缺氧 8 h 条件下七氟醚不同浓度(0%、2%、4%、6%)处理 30 min 对 NRF2、HO-1、HMGB1、IL-1β 蛋白表达的影响。 将 BV -2 细胞分为正常对照组、缺氧诱导组、6%七氟醚组、SnPP 组(NRF2 / HO-1 通路抑制剂-锡原卟啉)、6%七氟醚+ SnPP 组,计算活化细胞比例并检测细胞 NRF2 / HO-1/ HMGB1 通路蛋白及核转录因子-κB p65(NF-κB p65)、磷酸化 NF-κB p65(p-NF-κB p65)、IL-1β 蛋白表达水平。 结果 随着缺氧时间延长,活化细胞比例及 HMGB1、IL-1β 表达 逐渐升高,NRF2、HO-1 蛋白在 8~ 12 h 时下降至最低水平(P<0. 05),实验选用 8 h 为缺氧诱导条件。 随着七氟醚浓度升高,活化细胞比例、HMGB1、IL-1β 表达逐渐减少,NRF2、HO-1 逐渐升高(P<0. 05),且呈剂量依赖性,选取 6%七氟醚为处理浓度。 与正常对照组比较,缺氧诱导组 NRF2、HO-1 表达降低,活化细胞比例、HMGB1、IL-1β、p- NF-κB p65 / NF-κB p65 表达升高(P<0. 05)。 6%七氟醚组上述指标变化与缺氧诱导组相反(P<0. 05);SnPP 组上述 指标变化与缺氧诱导组一致且比缺氧诱导组严重(P<0. 05)。 6%七氟醚+SnPP 组上述指标变化与 6%七氟醚组相反(P<0. 05)。 结论 七氟醚可通过促进 NRF2 / HO-1 活化,抑制 HMGB1 表达,来减轻缺氧诱导的 MG 活化及炎症反应进程。

    Abstract:

    Objective To investigate the effects of sevoflurane on hypoxia-induced inflammatory responses of microglia and regulation of the nuclear factor erythroid 2-related factor 2 (NRF2) / heme oxygenase 1 (HO-1) / high mobility group protein B1 (HMGB1) pathway. Methods BV-2 mouse microglia were activated by inducing hypoxia for 0, 2, 4, 6, 8 and 12 h to establish an inflammation model. The activated cells were observed by inverted microscope, and the proportion of activated cells was calculated. Western blot were used to detect the expression levels of NRF2, HO-1, HMGB1 and interleukin (IL)-1β proteins in microglia. The optimal hypoxia time was 8 h. BV-2 microglia were activated under hypoxic conditions for 8 h; treated with different concentrations of sevoflurane (0%, 2%, 4% and 6%) for 30 min; and NRF2, HO-1, HMGB1, IL-1β protein expression was observed. BV-2 cells were divided into a control group, hypoxia- induction group, 6% sevoflurane group, SnPP group ( NRF2 / HO-1 pathway inhibitor stannous porphyrin), and 6% sevoflurane + SnPP group. The ratio of activated cells was calculated, and the protein expression levels of NRF2, HO-1, HMGB1, nuclear factor-κB p65 (NF-κB p65), phosphorylated NF-κB p65 (p-NF-κB p65) and IL-1β were determined. Results With prolonged hypoxia time, the proportion of activated cells and expression of HMGB1 and IL-1β gradually increased, and NRF2 and HO-1 proteins decreased to the lowest level at 8 ~ 12 h ( P< 0. 05). Therefore, the hypoxia- induction time of 8 h was chosen. With the increase in sevoflurane concentration, the proportion of activated cells and expression of HMGB1 and IL-1β gradually decreased, and NRF2 and HO-1 expression gradually increased (P< 0. 05). These effects were dose-dependent, and 6% sevoflurane was selected as the treatment concentration. Compared with that in the control group, the expression of NRF2 and HO-1 in the hypoxia-induced group decreased, and the proportion of activated cells and expression of HMGB1, IL-1β and p-NF-κB p65 / NF-κB p65 expression increased ( P< 0. 05). The changes in the above indices in the 6% sevoflurane group were opposite to those in the hypoxia-induced group (P<0. 05). The changes in the SnPP group were consistent with those in hypoxia-induced group and were more serious than those in hypoxia-induced group (P<0. 05). The changes in the above parameters in the 6% sevoflurane + SnPP group were opposite to those in 6% sevoflurane group ( P< 0. 05). Conclusions Sevoflurane treatment reduced hypoxia-induced microglial activation and inflammatory processes by promoting NRF2 / HO-1 activation and inhibiting HMGB1 expression.

    参考文献
    相似文献
    引证文献
引用本文

温翔宇,张军宏,朱存良.七氟醚调控 NRF2 / HO-1 / HMGB1 通路减轻缺氧诱导的小胶质细胞炎症反应[J].中国比较医学杂志,2022,32(2):66~73.

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2020-12-03
  • 在线发布日期: 2022-04-12
防诈骗提示!请勿点击不明链接或添加个人微信。编辑部所有邮箱后缀均为@cnilas.org
关闭