蛛网膜下腔出血后早期脑损伤中ROS和PDGFR活化的研究

廖忆思; 黄加尚; 谢延风; 石全红; 但炜; 蒋理; 向怡; 王宽; 詹彦

doi:10.16016/j.2097-0927.202202166

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蛛网膜下腔出血后早期脑损伤中ROS和PDGFR活化的研究

基础医学 | 更新时间：2026-01-09

- 蛛网膜下腔出血后早期脑损伤中ROS和PDGFR活化的研究
- Activation of PDGFR and ROS in early brain injury in rats after subarachnoid hemorrhage
- 陆军军医大学学报 2022年44卷第12期页码：1243-1248
- 作者机构：
  
  400016 重庆，重庆医科大学附属第一医院神经外科
- 作者简介：
  
  [詹彦，E-mail: zhan.yan2@hotmail.comZHAN Yan, E-mail: zhan.yan2@hotmail.com
- 基金信息：
  
  重庆市自然科学基金一般项目(cstc2015jcyjA10077)
- DOI：10.16016/j.2097-0927.202202166
  中图分类号： R363.21;R651.15;R743.35
- 收稿：2022-02-28，
  
  修回：2022-03-08，
  
  纸质出版：2022-06-30
- 稿件说明：
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廖忆思, 黄加尚, 谢延风, 等. 蛛网膜下腔出血后早期脑损伤中ROS和PDGFR活化的研究[J]. 陆军军医大学学报, 2022,44(12):1243-1248.

Yisi LIAO, Jiashang HUANG, Yanfeng XIE, et al. Activation of PDGFR and ROS in early brain injury in rats after subarachnoid hemorrhage[J]. Journal of Army Medical University, 2022, 44(12): 1243-1248.
廖忆思, 黄加尚, 谢延风, 等. 蛛网膜下腔出血后早期脑损伤中ROS和PDGFR活化的研究[J]. 陆军军医大学学报, 2022,44(12):1243-1248. DOI： 10.16016/j.2097-0927.202202166.

Yisi LIAO, Jiashang HUANG, Yanfeng XIE, et al. Activation of PDGFR and ROS in early brain injury in rats after subarachnoid hemorrhage[J]. Journal of Army Medical University, 2022, 44(12): 1243-1248. DOI： 10.16016/j.2097-0927.202202166.

摘要

目的

观察蛛网膜下腔出血(subarachnoid hemorrhage，SAH)后抑制血小板源性生长因子受体(platelet-derived growth factor receptor，PDGFR)活化及活性氧(reactive oxygen species，ROS)对早期脑损伤(Early brain injury，EBI)的作用，探讨它们影响SAH后早期脑损伤的可能机制。

方法

将成年雄性SD大鼠随机分为假手术组、SAH组、PDGF受体抑制组和ROS抑制组，每组12只。通过血管内穿刺法建立大鼠SAH模型，1 h后，治疗组动物通过腹腔注射相应的药物。在术后24、48 h，统计动物死亡率、体质量变化、神经行为学评分评估大脑功能障碍，测定脑含水量评估血脑屏障通透性。采用Western blot检测PDGFR及其磷酸化产物变化情况以及SAH后磷酸化JNK、MMP-9的表达。分别检测脂质和蛋白的氧化产物MDA含量和ROS水平。

结果

抑制PDGFR的激活、清除ROS都能使SAH后脑含水量降低(

0.05)，减少MMP-9表达(

0.05)，改善神经功能评分(

0.05)，减少ROS及MDA产生(

0.05)，减少JNK和c-Jun的磷酸化JNK和c-Jun的磷酸化。抑制ROS的生成能在一定程度上减少PDGFR的激活，抑制PDGFR的激活也能在一定程度上减少ROS的产生(

0.05)。

结论

大鼠蛛网膜下腔出血后，ROS参与了PDGFR的激活，PDGFR激活能进一步加重自由基损伤。JNK-MMP-9途径是早期脑损伤中引起血脑屏障破坏的重要途径。

Abstract

Objective

To investigate the effects of inhibiting the activation of platelet-derived growth factor receptor (PDGFR) and reactive oxygen species (ROS) on early brain damage (EBI) after subarachnoid hemorrhage (SAH)

and explore their possible acting mechanism in the process.

Methods

Adult male SD rats were randomly divided into sham operation group

SAH group

PDGF receptor inhibition group and ROS inhibition group

with 12 rats in each group. The rat model of SAH was established by intravascular puncture. In 1 h later

the rats in the treatment groups were injected with corresponding drugs by intraperitoneal injection. At 24 and 48 h after operation

animal mortality and body weight changes were observed

brain dysfunction was evaluated with neurobehavioral assessment

and brain water content was measured to evaluate blood-brain barrier permeability. Western blot analysis was used to detect the changes of PDGFR and phosphorylated PDGFR and the expression of p-JNK and p-MMP-9 after SAH. The oxidation products of lipids and proteins

malondialdehyde (MDA) and ROS were also detected.

Results

Both inhibiting the activation of PDGFR and scavenging ROS reduced brain water content after SAH (

0.05)

decreased the expression of MMP-9 (

0.05)

improved the neurological function score (

0.05)

reduced the production of ROS and MDA (

0.05)

and decreased the phosphorylation of JNK and c-Jun. Inhibiting the generation of ROS suppressed the activation of PDGFR to a certain extent

and inhibiting the activation of PDGFR also reduced the generation of ROS to a certain extent (

0.05).

Conclusion

After SAH in rats

ROS is involved in the activation of PDGFR

and its activation can further aggravate free radical damage. The JNK-MMP-9 pathway is indeed an important pathway that causes blood-brain barrier disruption in EBI.

关键词

Keywords

references

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