基础医学与临床 ›› 2022, Vol. 42 ›› Issue (8): 1206-1212.doi: 10.16352/j.issn.1001-6325.2022.08.1206

• 研究论文 • 上一篇    下一篇

七氟醚减轻蛛网膜下腔出血大鼠早期脑损伤

张敏, 邢丹丹, 康文越, 林慧*   

  1. 海南省人民医院 海南医学院附属海南医院 麻醉科,海南 海口 570000
  • 收稿日期:2021-05-28 修回日期:2021-11-12 出版日期:2022-08-05 发布日期:2022-08-01
  • 通讯作者: *linhui7811@126.com
  • 基金资助:
    海南省科学技术厅资助项目(2019RC365)

Sevoflurane alleviates early brain injury in rats with subarachnoid hemorrhage

ZHANG Min, XING Dan-dan, KANG Wen-yue, LIN Hui*   

  1. Department of Anesthesiology, Hainan Affiliatal Hospital of Hainan Medical University, Hainan General Hospital,Haikou 570000, China
  • Received:2021-05-28 Revised:2021-11-12 Online:2022-08-05 Published:2022-08-01
  • Contact: *linhui7811@126.com

摘要: 目的 探讨七氟醚(Sev)对蛛网膜下腔出血(SAH)大鼠早期脑损伤(EBI)的保护机制。方法 将大鼠随机分为假手术组(sham组)、模型组(model组)(用血管内穿刺法建立SAH模型)、Sev低(Sev-L,1.5%)、高剂量组(Sev-H,3%)、Sev+Wnt/β-catenin信号通路的特异性抑制剂DKK1(Sev 3%+DKK1 5 μg/kg)组(在模型制备前30 min,侧脑室注射DKK1),每组18只。24 h后使用改良的Garcia量表对大鼠神经功能进行评分;伊文思蓝(EB)检测血脑屏障通透性,并通过SAH分级系统评估SAH的严重程度;计算脑组织含水量(BWC);TUNEL免疫荧光染色检测神经元凋亡;Western blot检测脑组织Wnt3a、GSK-3β、p-GSK-3β、β-catenin、ZO-1、occludin、claudin-5、MMP-9、Bcl-2、Bax蛋白表达。结果 与sham组相比,model组大鼠神经功能评分、脑组织Bcl-2、occludin、ZO-1、claudin-5、Wnt3a、β-catenin表达显著降低(P<0.05);SAH评分、EB渗出量、细胞凋亡率、脑组织Bax、MMP-9表达、p-GSK-3β/GSK-3β比值显著升高(P<0.05);与Model组相比,Sev-L、Sev-H组大鼠神经功能评分、脑组织Bcl-2、occludin、ZO-1、claudin-5、Wnt3a、β-catenin表达明显升高(P<0.05);SAH评分、EB渗出量、细胞凋亡率、脑组织Bax、MMP-9表达、p-GSK-3β/GSK-3β比值明显降低(P<0.05);而DKK1可明显削弱Sev对SAH后EBI的保护作用。结论 Sev可能通过激活Wnt/β-catenin通路,改善BBB,抑制神经元凋亡,减轻SAH后的EBI。

关键词: 七氟醚, 蛛网膜下腔出血, 血脑屏障, 神经元凋亡, Wnt/β-连环蛋白

Abstract: Objective To explore the protective mechanism of sevoflurane (Sev) on early brain injury (EBI) in rats with subarachnoid hemorrhage (SAH). Methods Rats were randomly divided into sham operation group (sham group), model group , Sev low dose(Sev-L, 1.5%)and high dose (Sev-H, 3%) groups, Sev+Wnt/β-catenin signaling pathway specific inhibitor DKK1 group (Sev 3%+DKK1 5 μg/kg) with 18 rats in each. After 24 hours, the neurological function of rats was scored with the improved Garcia scale, the permeability of the blood-brain barrier was detected with Evans blue (EB), and the severity of SAH was evaluated with the SAH grading system; the brain tissue water content (BWC) was calculated; the neuronal apoptosis was detected with TUNEL immunofluorescence staining; the protein expression of Wnt3a, GSK-3β, p-GSK-3β, β-catenin, ZO-1, occludin and claudin-5, MMP-9, Bcl-2, Bax in brain tissue was detected with Western blot. Results Compared with the sham group, the neurological score, expression of Bcl-2, occludin, ZO-1, claudin-5, Wnt3a, and β-catenin in brain tissues in the model group reduced significantly (P<0.05), the SAH score, EB exudation, cell apoptosis rate, expression of Bax, MMP-9, and p-GSK-3β/GSK-3β ratio in brain tissue increased significantly(P<0.05); compared with model group, the neurological score, expression of Bcl-2, occludin, ZO-1, claudin-5, Wnt3a, and β-catenin in brain tissues in the Sev-L group and Sev-H group increased significantly(P<0.05), the SAH score, EB exudation, cell apoptosis rate, expression of Bax, MMP-9, and p-GSK-3β/GSK-3β ratio in brain tissue reduced significantly (P<0.05); DKK1 significantly weakened protective effect of Sev on EBI after SAH. Conclusions Sev may activate Wnt/β-catenin pathway, improve BBB, inhibit neuronal apoptosis and reduce EBI after SAH.

Key words: sevoflurane, subarachnoid hemorrhage, blood-brain barrier, neuronal apoptosis, Wnt/β-catenin

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