TRPV4通道抑制剂对创伤性脑损伤后血脑屏障破坏的保护作用  

Protective effect of transient receptor potential vanilloid 4 channel inhibitor on blood-brain barrier disruption after traumatic brain injury

作　　者：孔繁皓 张鸿洋 张蔚 赵一诺 丁晓慧[3] 杨智航[4] 苏秋香[5] 解辉[3] KONG Fanhao;ZHANG Hongyang;ZHANG Wei;ZHAO Yinuo;DING Xiaohui;YANG Zhihang;SU Qiuxiang;XIE Hui(Shenyang Medical College,Shenyang 110034,China;不详;Department of Histology and Embryology,Shenyang Medical College;Department of Physiology,Shenyang Medical College;Morphological Center,Shenyang Medical College)

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 [3]沈阳医学院组织胚胎学教研室 [4]沈阳医学院生理学教研室 [5]沈阳医学院形态学中心

出　　处：《沈阳医学院学报》2022年第2期196-199,共4页Journal of Shenyang Medical College

基　　金：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);沈阳医学院大学生科研立项(No.20209019,20219049)。

摘　　要：目的:探讨TRPV4通道抑制剂对创伤性脑损伤(traumatic braininjury,TBI)后血脑屏障(blood-brainbarrier,BBB)破坏的作用和可能机制。方法:采用自由落体致伤法制备大鼠TBI模型;采用伊文思蓝定量评估法检测TRPV4抑制剂HC067047对TBI后不同时间点BBB通透性变化的影响;应用干湿重法检测HC067047对各组大鼠脑组织含水量的影响;采用Westernblot法检测脑损伤区域微血管内皮紧密连接蛋白Occludin和Caudin-5表达的变化。结果:大鼠TBI后,BBB通透性明显增加,于3 d达峰值。给予TRPV4抑制剂HC067047后,其BBB通透性较相同时间点的假手术组明显降低;同时大鼠TBI后3 d,脑组织含水量明显增加,并且Occludin和Caudin-5的表达明显减少;给予HC067047处理后,脑组织含水量和Occludin、Caudin-5的表达明显恢复,差异均有统计学意义。结论:TRPV4通道抑制剂对TBI后BBB破坏具有保护作用,其机制可能是通过恢复脑损伤区域微血管内皮紧密连接蛋白Occludin和Caudin-5的表达实现。Objective:To investigate the role and possible mechanism of transient receptor potential vanilloid 4(TRPV4)channel inhibitor on blood-brain barrier(BBB)disruption after traumatic brain injury(TBI).Methods:The model of TBI in rats were prepared,and the effect of TRPV4 channel inhibitor HC067047 on permeability change of BBB at different time points after TBI were determined by Evans blue method.The effect of HC067047 on brain water content was detected by dry wet weight method.And the expressions of tight junction proteins Occludin and Claudin 5 of microvascular endothelium in brain injury area in rats were determined by Western blot.Results:After TBI in rats,BBB permeability increased obviously,and peaked at 3 d.After treatment with HC067047,BBB permeability decreased significantly compared with the sham group at the same time points.At 3 d after TBI,brain water content increased obviously,and expression levels of Occludin and Claudin 5 decreased obviously.After treatment with HC067047,brain water content and expression levels of Occludin and Claudin-5 were recovered,the differences were statistically significant.Conclusion:Inhibition of TRPV4 channel can protect the BBB disruption after TBI in rats,the mechanism may be associated with the recovered expressions of Occludin and Claudin-5 of microvascular endothelium in brain injury area.

关 键 词：TRPV4通道 创伤性脑损伤 血脑屏障 

分 类 号：R651.15[医药卫生—外科学]