解放军医学杂志2024，Vol.49Issue(9)：1055-1061,7.DOI:10.11855/j.issn.0577-7402.0848.2023.1227
右美托咪定对大鼠围手术期脑卒中模型的治疗作用及其机制
Therapeutic effect and its mechanism of dexmedetomidine on the rat model of perioperative stroke
摘要
Abstract
Objective To investigate the effect of dexmedetomidine(Dex)on the rat model of perioperative stroke and its mechanism.Methods One hundred male rats were randomly divided into sham group,middle cerebral artery occlusion(MCAO)group,low dose Dex[Dex-L,0.5 µg/(kg·h)]group,medium dose Dex[Dex-M,2 µg/(kg·h)]group,high dose Dex[Dex-H,10 µg/(kg·h)]group,20 rats in each group.A rat model of perioperative stroke was established by middle cerebral artery occlusion.Dex was injected intravenously at different doses during ischemia.After 24 h,the neurological function of the rats was evaluated.Then,the rats were sacrificed and the peripheral blood and whole brain tissue were collected,ischemic core area tissue was separated from some brain tissues and the cerebral infarction area was observed by TTC staining.The inflammatory cytokine contents in serum and ischemic core area were measured by ELISA.In addition,the expressions of formyl peptide receptor 1(FPR1),transmembrane protein 119(TMEM119),CD31 and VE-cadherin proteins were assayed by immunofluorescence,and the expressions of FPR1,nuclear factor-κB(NF-κB)and NLRP3 proteins by Western blotting in the ischemic core area.Results Compared with sham group,the proportion of cerebral infarction area and neurological scores in the MCAO group were significantly increased,and the contents of interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α in the serum and the ischemic core area were significantly increased,the expressions of FPR1,TMEM119,p-NF-κB,NLRP3,CD31 and VE-cadherin in the ischemic core were significantly increased(P<0.001),and there was obvious co-expression of FPR1 and TMEM119.Compared with MCAO group,the proportion of cerebral infarction area and neurological scores in the Dex-M and Dex-H groups were significantly decreased,and the contents of IL-1β,IL-6 and TNF-α in serum and brain ischemic core area were significantly decreased,the expressions of FPR1,TMEM119,p-NF-κB,NLRP3,CD31 and VE-cadherin in the ischemic core were significantly decreased(P<0.001).Conclusions Dex can significantly alleviate perioperative stroke injury.The mechanism may be due to inhibiting the expression of FPR1 protein,activation of microglia cells and cerebral collateral circulation angiogenesis.关键词
甲酰肽受体1/右美托咪定/围手术期脑卒中/小胶质细胞/血管新生Key words
formyl peptide receptor 1/dexmedetomidine/ischemic stroke/microglia/angiogenesis分类
医药卫生引用本文复制引用
李佩佩,马刚,屈保福,张彩霞..右美托咪定对大鼠围手术期脑卒中模型的治疗作用及其机制[J].解放军医学杂志,2024,49(9):1055-1061,7.基金项目
This work was supported by the Natural Science Foundation of Ningxia(2022AAC02061) 宁夏自然科学基金项目(2022AAC02061) （2022AAC02061）
