TRPV4通道抑制剂对大鼠创伤性脑损伤后血脑屏障破坏的保护机制研究
The protective mechanism of TRPV4 channel inhibitor on blood-brain barrier damage after traumatic brain injury in rats
孔繁皓 1张鸿洋 1张蔚 1唐梦泽 1王樱桥 1李想 1丁晓慧 2杨智航 3解辉2
作者信息
- 1. 沈阳医学院基础医学院,辽宁 沈阳 110034
- 2. 沈阳医学院基础医学院组织胚胎学教研室,辽宁 沈阳 110034
- 3. 沈阳医学院基础医学院生理学教研室,辽宁 沈阳 110034
- 折叠
摘要
目的:探讨TRPV4通道抑制剂对创伤性脑损伤(traumatic brain injury,TBI)后血脑屏障(blood-brain barrier,BBB)破坏的具体保护机制.方法:制备大鼠TBI模型;应用TRPV4通道抑制剂HC067047或PKC-δ抑制剂Rottlerin检测TBI后BBB通透性、大鼠神经功能评分和脑损伤区域微血管内皮紧密连接蛋白ZO-1和ZO-2表达的变化.结果:与假手术组比较,大鼠TBI后,BBB通透性明显增加,脑神经功能评分降低,同时紧密连接蛋白ZO-1和ZO-2的表达明显减少,差异均有统计学意义(P＜0.05);与TBI模型组比较,给予HC067047或Rottlerin后,其BBB通透性、神经功能评分、紧密连接蛋白ZO-1和ZO-2的改变均被部分逆转,差异均有统计学意义(P＜0.05).结论:TBI介导的BBB损伤可能通过TRPV4通道调控PKC-δ信号通路进而影响紧密连接蛋白ZO-1和ZO-2的表达实现;抑制TRPV4通道功能或PKC-δ信号分子均能够部分减轻TBI诱导的BBB损伤,本研究可能为临床TBI的治疗提供新思路.
Abstract
Objective:To investigate the protective mechanism of TRPV4 channel inhibitor on blood-brain barrier(BBB)damage after traumatic brain injury(TBI).Methods:The TBI rat model was established.TRPV4 channel inhibitor HC067047 or PKC-δ inhibitor Rottlerin was used to detect changes in BBB permeability,neurological function score,and the expression of microvascular endothelial tight junction proteins ZO-1 and ZO-2 in brain injury areas after TBI.Results:Compared with the Sham group,BBB permeability significantly increased,brain neurological function score significantly decreased,and the expression of ZO-1 and ZO-2 significantly decreased in TBI group(P＜0.05).Compared with the TBI group,after administration of HC067047 or Rottlerin,changes in BBB permeability,brain neurological function score,the expression of ZO-1 and ZO-2 were partially reversed(P＜0.05).Conclusions:TBI-induced BBB injury may be mediated by TRPV4 channel regulating PKC-δ signaling pathway to affect the expression of tight junction proteins ZO-1 and ZO-2.Inhibition of TRPV4 channel function or PKC-δ signal molecule can partially alleviate BBB damage induced by TBI.This study may provide new ideas for the treatment of clinical TBI.
关键词
TRPV4通道/PKC-δ信号通路/创伤性脑损伤/血脑屏障Key words
TRPV4 channel/PKC-δ signaling pathway/traumatic brain injury/blood-brain barrier引用本文复制引用
基金项目
沈阳医学院大学生科研立项项目(20219049)
辽宁省自然科学基金指导项目(2019-ZD-0340)
辽宁省科技计划指导项目(20180550093)
出版年
2024
国家科技期刊平台
NSTL
万方数据