实用医学杂志 ›› 2021, Vol. 37 ›› Issue (17): 2182-2186.doi: 10.3969/j.issn.1006⁃5725.2021.17.003

• 基础研究 • 上一篇    下一篇

瞬态受体电位香草酸1通过抑制p⁃JNK和p⁃p38 MAPK信号通路减轻小鼠脑缺血后血脑屏障损伤及焦虑样行为的机制

张震1,2 王梅芳3 宋远见1,2   

  1. 1 徐州医科大学遗传学学科(江苏徐州 221004);2 徐州市医学遗传与工程研究中心(江苏徐州 221004); 3 常熟市第二人民医院麻醉科(江苏常熟 215500)

  • 出版日期:2021-09-10 发布日期:2021-09-10
  • 通讯作者: 王梅芳 E⁃mail:2003wmf@163.com;宋远见 E⁃ mail:yjsong@xzhmu.edu.cn
  • 基金资助:

    江苏省“六大人才高峰”高层次人才培养对象项目基金资助(编号:WSN⁃089

Mechanism of TRPV1 attenuating blood ⁃brain barrier damage and anxiety ⁃like behaviors after cerebral ischemia in mice by inhibiting p ⁃JNK and p ⁃p38 MAPK signaling pathways

ZHANG Zhen*,WANG Mei⁃ fang,SONG Yuanjian.   

  1. Department of Genetics,Xuzhou Medical University,Xuzhou 221004,China;*Xuzhou Med⁃ ical Genetics and Engineering Research Center,Xuzhou 221004,China

  • Online:2021-09-10 Published:2021-09-10
  • Contact: WANG Meifang E⁃mail:2003wmf@163.com;SONG Yuanjian E⁃mail:yjsong@xzhmu.edu.cn

摘要:

目的 探讨瞬态受体电位香草酸 1(TRPV1)对小鼠脑缺血再灌注后血脑屏障损伤及焦虑样行为的作用及机制。方法 线栓法构建大脑中动脉栓塞(MCAO)模型。侧脑室注射Capsazepine(CPZ,7.5 μg/ 3 μL)。HE 染色检测杏仁核区病理变化;免疫荧光染色检测杏仁核区血管损伤情况;免疫印迹技术检测 p⁃JNK、p⁃p38 MAPK的水平;高架十字迷宫检测焦虑样行为。结果 (1)与I/R组比较,I/R+CPZ组在高架十字 迷宫开臂的移动距离和停留时间显著升高(P < 0.001)。(2)与I/R组比较,I/R+CPZ组HE染色细胞核固缩减 少,水肿减少。(3)与 I/R 组比较,I/R+CPZ Claudin5 表达增多。(4)与 I/R 组比较,I/R+CPZ p⁃JNK、p⁃p38 MAPK水平明显降低(P < 0.05)。结论 抑制TRPV1能够通过降低p⁃JNK、p⁃p38 MAPK水平减轻小鼠脑缺血 后血脑屏障损伤及焦虑样行为。

关键词:

瞬态受体电位香草酸1, 脑缺血, 血脑屏障, 焦虑

Abstract:

Objective To explore the effect of TRPV1 on blood⁃brain barrier injury and anxiety⁃like behaviors after cerebral ischemia⁃reperfusion in mice and its and mechanism. Methods A model of middle cerebral artery embolism(MCAO)was constructed by use of thread embolization. Capsazepine(CPZ)of 7.5 μg/3 uL was injected into the lateral ventricle. HE staining was used to detect pathological changes in amygdala;Immunofluores⁃ cence staining was applied to detect vascular damage in amygdala;Western blot was used to detect levels of p⁃JNK and p ⁃ p38 MAPK;High plus maze was used to detect anxiety ⁃like behaviors. Results As compared with I/R group,the moving distance and length of stay in the open arms of high plus maze in I/R+CPZ group increased significantly(P < 0.001). HE staining showed that nucleus pyknosis and edema,as compared with I/R group were reduced in I/R + CPZ group. As compared with I/R group,Claudin5 expression was increased in I/R + CPZ group,whereas levels of p⁃JNK and p⁃p38 MAPK were significantly reduced(P < 0.05). Conclusions Inhibition of TRPV1 can alleviate damage in blood⁃brain barrier and anxiety⁃like behaviors after cerebral ischemia in mice by reducing levels of p⁃JNK and p⁃p38 MAPK.

Key words:

TRPV1, brain ischemia, blood brain barrier, anxiety