Propofol alleviates the disruption of blood-brain barrier caused by cerebral ischemia

ZHANG Hua-shan; ZHANG Yuan-ze

doi:10.11659/jjssx.11E022160

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Propofol alleviates the disruption of blood-brain barrier caused by cerebral ischemia

Basic Research | 更新时间：2024-01-22

- Propofol alleviates the disruption of blood-brain barrier caused by cerebral ischemia
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 33, Issue 1, Pages: 14-18(2024)
- 作者机构：
  
  1.聊城市第二人民医院/山东第一医科大学附属聊城二院麻醉科，山东临清 252601
  2.武汉市普仁医院麻醉科，湖北武汉 430081
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.11E022160
  CLC： R971.2
- Published：25 January 2024，
  
  Received：29 November 2022，
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张华山,张元泽.丙泊酚减轻脑缺血破坏血脑屏障的实验研究[J].局解手术学杂志,2024,33(01):14-18.

ZHANG Hua-shan,ZHANG Yuan-ze.Propofol alleviates the disruption of blood-brain barrier caused by cerebral ischemia[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(01):14-18.
张华山,张元泽.丙泊酚减轻脑缺血破坏血脑屏障的实验研究[J].局解手术学杂志,2024,33(01):14-18. DOI： 10.11659/jjssx.11E022160.

ZHANG Hua-shan,ZHANG Yuan-ze.Propofol alleviates the disruption of blood-brain barrier caused by cerebral ischemia[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(01):14-18. DOI： 10.11659/jjssx.11E022160.

摘要

目的

探讨丙泊酚对脑缺血大鼠血脑屏障的保护作用及其机制。

方法

将48只10周龄雄性SD大鼠随机分为假手术组、脑缺血组、丙泊酚组、丙泊酚+LY294002组。丙泊酚+LY294002组大鼠于建模前24 h经侧脑室注射PI3K抑制剂LY294002（0.3 mg·kg

-1

），其余各组大鼠注射生理盐水（10 μL）。脑缺血组、丙泊酚组、丙泊酚+LY294002组大鼠通过颈动脉线栓阻塞法构建脑缺血模型，假手术组大鼠仅分离出颈总动脉，结扎颈外动脉，不进行其他处理。建模期间，丙泊酚组与丙泊酚+LY294002组大鼠尾静脉滴注丙泊酚（10 mg·kg

-1

），假手术组与丙泊酚组注射生理盐水。24 h后，采用Zea Longa法评估大鼠神经功能，采用TTC染色测定大鼠脑梗死面积，干湿重法检测大鼠脑水肿程度，EB示踪法评估血脑屏障完整性，ELISA法检测脑脊液中炎症细胞因子水平，Western blot检测PI3K/AKT信号通路蛋白及血脑屏障紧密连接蛋白Claudin-5、Occludin表达。

结果

脑缺血导致大鼠神经功能评分升高，脑组织出现局部梗死。与假手术组相比，脑缺血组大鼠脑组织中EB含量增加，脑水肿程度升高，脑脊液中炎症细胞因子含量增加；给予丙泊酚能够明显降低神经功能评分，减少脑梗死面积，抑制EB穿透血脑屏障，降低脑水肿程度，减少炎症细胞因子释放，上调PI3K/AKT信号通路蛋白与紧密连接蛋白Claudin-5、Occludin表达；LY294002则明显逆转了丙泊酚的上述作用。

结论

丙泊酚可通过PI3K/AKT信号通路维持紧密连接蛋白Claudin-5、Occludin蛋白表达，保护血脑屏障结构与功能完整性，降低脑水肿程度，避免其他炎症细胞因子进入脑组织，减少脑梗死，减轻脑缺血造成的神经功能损伤。

Abstract

Objective

To investigate the protective effect and mechanism of propofol on the blood-brain barrier in rats with cerebral ischemia.

Methods

A total of 48 10-week-old male SD rats were randomly divided into the sham group，the cerebral ischemia group，the propofol group and the propofol+LY294002 group. Twenty-four hours before the induction of the model，the rats in the propofol+LY294002 group were intracerebroventricularly injected with PI3K inhibitor LY294002 （0.3 mg·kg

-1

），and the rats in the other groups were administrated with saline （10 μL）. Rats in the cerebral ischemia group，the propofol group and the propofol+LY294002 group established cerebral ischemia models by carotid artery occlusion. Rats in the sham group only isolated the common carotid artery and ligated the external carotid artery without other treatment. During the modeling period，the rats in the propofol group and the propofol+LY294002 group were given propofol （10 mg·kg

-1

） via the tail vein，and the sham group and the propofol group were treated with saline. After 24 hours，the neurological function of rats was evaluated by Zea Longa method； the area of cerebral infarction was detected by TTC staining； the degree of cerebral edema was detected by the dry-wet weight method. EB tracer method was used to evaluate the integrity of the blood-brain barrier； ELISA was used to detect inflammatory cytokines in cerebrospinal fluid； Western blot was used to detect the expression of PI3K/AKT signaling pathway proteins and blood-brain barrier tight junction proteins Claudin-5 and Occludin.

Results

Cerebral ischemia led to the increase of neurological function scores and local infarction of brain tissues in rats. Compared with the sham group，the EB content in the brain tissue of rats in the cerebral ischemia group increased，the degree of brain edema increased，and the content of inflammatory cytokines in the cerebrospinal fluid increased. And the use of propofol could significantly decrease the neurological function scores，reduce the area of cerebral infarction，inhibit EB penetrating blood-brain barrier，reduce the degree of brain edema，reduce the release of inflammatory cytokines，and up-regulate the expression of PI3K/AKT signaling pathway proteins and tight junction proteins Claudin-5 and Occludin. LY294002 significantly reversed the above effects of propofol.

Conclusion

Propofol can maintain the expression of tight junction proteins Claudin-5 and Occludin through the PI3K/AKT signaling pathway，protect the structural and functional integrity of blood-brain barrier，reduce the degree of brain edema，prevent other inflammatory cytokines into the brain tissue，reduce cerebral infarction，and alleviate the neurological functional damage caused by cerebral ischemia.

关键词

丙泊酚脑缺血血脑屏障炎症细胞因子PI3K/AKT信号通路

Keywords

propofolcerebral ischemiablood-brain barrierinflammatory cytokinePI3K/AKT signaling pathway

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