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

作　　者：孔繁皓 张鸿洋 张蔚 唐梦泽 王樱桥 李想 丁晓慧[2] 杨智航[3] 解辉[2] KONG Fanhao;ZHANG Hongyang;ZHANG Wei;TANG Mengze;WANG Yingqiao;LI Xiang;DING Xiaohui;YANG Zhihang;XIE Hui(Undergraduate Majoring in Clinical Medicine,Shenyang Medical College,Shenyang 110034,China;Undergraduate Majoring in Psychiatry,Shenyang Medical College,Shenyang 110034,China;Department of Histology and Embryology,Shenyang Medical College,Shenyang 110034,China;Department of Physiology,Shenyang Medical College,Shenyang 110034,China)

机构地区：[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

出　　处：《沈阳医学院学报》2024年第2期175-178,共4页Journal of Shenyang Medical College

基　　金：沈阳医学院大学生科研立项(No.20219049);辽宁省自然基金指导计划(No.2019-ZD-0340);辽宁省科学技术基金指导项目(No.20180550093)。

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。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-δinhibitor 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-δsignaling pathway to affect the expression of tight junction proteins ZO-1 and ZO-2.Inhibition of TRPV4 channel function or PKC-δsignal 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 

分 类 号：R743.31[医药卫生—神经病学与精神病学]