天津医药

天津医药 ›› 2021, Vol. 49 ›› Issue (11): 1158-1162.doi: 10.11958/20210847

• 实验研究 • 上一篇    下一篇

基于NF-κB/ICAM-1通路探讨右美托咪定对子痫前期大鼠的神经保护作用

张雷，朱咏仪，赵年章，梁少玲   

  1. 广州医科大学附属第五医院麻醉科（邮编510700）
  • 收稿日期:2021-04-12 修回日期:2021-07-27 出版日期:2021-11-15 发布日期:2021-11-19
  • 基金资助:
    广东省医学科学技术研究基金项目（B2020008）

The neuroprotective effect of dexmedetomidine on preeclampsia rats based on NF-κB/ICAM-1 pathway

ZHANG Lei, ZHU Yong-yi ZHAO Nian-zhang, LIANG Shao-ling   

  1. Department of Anesthesiology, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China
  • Received:2021-04-12 Revised:2021-07-27 Published:2021-11-15 Online:2021-11-19

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摘要： 目的　基于核因子-κB（NF-κB）/细胞间黏附分子-1（ICAM-1）通路探讨右美托咪定（DEX）对子痫前期大鼠的神经保护作用。方法　SD孕鼠随机分为对照组，模型组，DEX低、中、高剂量组，每组10只。除对照组外，其余各组孕鼠于妊娠第10~20天每日腹腔注射同型半胱氨酸（Hcy，200 mg/kg）及隔日背部皮下注射谷氨酸单钠（MSG，1 g/kg）制备子痫前期模型，在妊娠第10~20天，DEX低、中、高剂量组分别腹腔注射7.5、15.0、30.0 μg/kg 的DEX。神经行为学实验评估大鼠行为学缺损情况；酶联免疫吸附试验（ELISA）法检测脑脊液中S100B、铁蛋白和脑组织炎性因子白细胞介素（IL）-1β、肿瘤坏死因子-α（TNF-α）及IL-6表达水平；TUNEL染色检测脑组织细胞凋亡情况；Western blot检测大鼠脑组织NF-κB/ICAM-1通路相关蛋白表达。结果　与对照组相比，模型组大鼠脑组织细胞凋亡现象严重，行为学缺损评分，脑脊液中S100B与铁蛋白，脑组织IL-1β、TNF-α、IL-6含量，p-NF-κB/NF-κB、ICAM-1蛋白表达水平显著升高（P＜0.05）；与模型组相比，DEX低、中、高剂量组大鼠凋亡细胞比例较低，行为学缺损评分，脑脊液中S100B与铁蛋白，脑组织IL-1β、TNF-α、IL-6含量，p-NF-κB/NF-κB、ICAM-1蛋白表达水平下降（P＜0.05），且DEX各组之间呈剂量依赖性。结论　DEX对子痫前期大鼠神经细胞有保护作用，其机制可能与抑制NF-κB/ICAM-1信号激活、炎性因子释放及脑神经细胞凋亡有关。

关键词: NF-κB, 胞间黏附分子1, 右美托咪定, 神经保护, 子痫前期

Abstract: Objective　To investigate the neuroprotective effect of dexmedetomidine (DEX) on preeclampsia rats, based on the nuclear factor-κB (NF-κB)/intercellular adhesion molecule-1 (ICAM-1) pathway. Methods　SD pregnant rats were randomly divided into the control group, the model group, the low-, middle- and high-dose DEX groups, with 10 rats in each group. Except for the sham operation group, the other groups were intraperitoneally injected with homocysteine (Hcy, 200 mg/kg) daily and subcutaneously injected with monosodium glutamate (MSG, 1 g/kg) on the back every other day to prepare the preeclampsia model. During the 10th day to the 20th day of pregnancy, the low-, middle- and high-dose DEX groups were intraperitoneally injected 7.5, 15.0 and 30.0 μg/kg of DEX for 10 days. Neurological function score was used to evaluate the behavioral defects of rats. Enzyme-linked immunosorbent assay (ELISA) was used to detect the S100B and ferritin in cerebrospinal fluid, the expression levels of brain tissue inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). TUNEL staining was used to detect the apoptosis of brain tissue. Western blot assay was used to detect the expression levels of NF-κB/ICAM-1 pathway related proteins in brain tissue. Results　Compared with those in the control group, the apoptosis of brain tissue was serious, the neurological function score, S100B and ferritin in cerebrospinal fluid, contents of IL-1β, TNF-α, IL-6 in brain tissue, protein expression levels of p-NF-κB/NF-κB and ICAM-1 were significantly higher in the model group (P＜0.05). Compared with those in the model group, the proportion of apoptotic cells was less in the low-, medium-, and high-dose DEX groups, the neurological function score, S100B and ferritin in cerebrospinal fluid, contents of IL-1β, TNF-α, IL-6 in brain tissue, protein expression levels of p-NF-κB/NF-κB and ICAM-1 were significantly lower (P＜0.05). There was a dose-dependent relationship between the DEX groups. Conclusion　DEX has a therapeutic effect on nerve cells, and its mechanism may be related to the inhibition of the NF-κB/ICAM-1 signal activation, the inflammatory factor release and the apoptosis of brain nerve cells.

Key words: NF-kappa B, intercellular adhesion molecule-1, dexmedetomidine, neuroprotection, preeclampsia