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

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

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、30.0μg/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。

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 ther day to prepare the preeclampsia model.During the 10 th day to the 20 th day of pregnancy,the low-,middle-and high-dose DEX groups were intraperitoneally injected 7.5,15.0 and 30.0μg/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 S100 B 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,S100 B 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,S100 B 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.