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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

28卷

期数:

2022年06期

页码:

615-620

栏目:

基础医学

出版日期:

2022-11-20

文章信息/Info

Title:

Mechanism of AG490 improving neurological function after ischemic stroke

文章编号:

1006-8147(2022)06-0615-06

作者:

张薇¹; 辛灵 ¹; 阎涛¹; 2

张薇1，辛灵 1，阎涛1，2

Author(s):

ZHANG Wei¹; XING Ling¹; YAN Tao¹; 2

（1.Tianjin Neurological Institute; 2. Department of Neurology，General Hospital，Tianjin Medical University，Tianjin 300052，China）

关键词:

缺血性脑卒中; JAK2-STAT3; 炎性反应; 自噬

Keywords:

ischemic stroke; JAK2-STAT3; inflammatory response; autophagy

分类号:

R392.5

DOI:

-

文献标志码:

A

摘要:

目的：探讨AG490改善缺血性脑卒中后神经功能的机制研究。方法：采用C57BL/6J成年雄性小鼠构建光化学法局灶性大脑皮层缺血性脑卒中模型，随机分为Control组、Stroke组、DMSO组和AG490组，每组18只。术后1、3、7、14 d进行神经功能评分。术后第3天进行荧光定量PCR检测小鼠脑组织中Janus 激酶2（JAK2）、信号转导与转录激活因子3（STAT3）、白细胞介素-1α（IL-1α）、单核细胞趋化蛋白-1（MCP-1）、补体C1q、基质金属蛋白酶-9（MMP-9）、紧密连接蛋白（Occludin、Claudin5和ZO-1）的表达，免疫印迹检测自噬相关蛋白（LC3Ⅱ/Ⅰ、P62/SQSTM1、Beclin-1）以及Occludin、Claudin5、ZO-1表达水平变化。结果：与Stroke组和DMSO组相比，AG490组在第3天、 7 天和 14 天错步/总步比例降低（F=3.704、9.199、10.83，均P＜0.05），JAK2、STAT3 mRNA表达下调（F=6.331、7.168，均P＜0.05），血脑屏障相关蛋白（Occludin、Claudin5、ZO-1）mRNA表达（F=7.648、29.83、25.08，均P＜0.05）和蛋白表达水平上调（F=12.42、10.88、14.32，均P＜0.05），MMP-9 mRNA表达水平下调（F=9.790，P＜0.01），脑组织炎性因子IL-1α、MCP-1和C1q表达下调（F=5.486、5.455、4.862，均P＜0.05），自噬相关蛋白LC3Ⅱ/LC3Ⅰ、Beclin-1表达上调（F=6.092、15.52，均P＜0.05），P62 /SQSTM1表达下调（F=8.143，P＜0.05）。结论：AG490通过抑制JAK2-STAT3通路的促炎作用并调节自噬，减轻血脑屏障损伤，改善缺血性脑卒中后的神经功能障碍。

Abstract:

Objective： To investigate the mechanism of AG490 improving neurological function after ischemic stroke. Methods： C57BL/6J adult male mice were used to construct a photochemically induced ischemic stroke model. They were randomly divided into the Control group，Stroke group，DMSO group，and AG490 group，with 18 mice in each group. Neurological function scores were performed 1，3，7，and 14 days after the operation. The expressions of Janus kinase 2（JAK2），signal transducer and activator of transcription 3（STAT3），interleukin-1 α（IL-1α），monocyte chemoattractant protein-1（MCP-1），complement C1q，matrix metalloproteinase-9（MMP-9），tight junction proteins（occludin，claudin5，and ZO-1） in mouse brain tissue were detected by real-time quantitative PCR on the 3rd day after operation. Autophagy-related proteins（LC3Ⅱ/Ⅰ，P62/SQSTM1，Beclin-1） and tight junction proteins（Occludin，Claudin5，ZO-1） were detected by Western blotting. Results： Compared with the Stroke group and the DMSO group，AG490 treatment significantly decreased the ratio of staggered steps/total steps on days 3，7 and 14（F=3.704，9.199，10.83，all P＜0.05）. AG490 down-regulated the mRNA expression of JAK2 and STAT3（F=6.331，7.168，both P＜0.05）.Blood-brain barrier-related indicators（Occludin，Claudin5，ZO-1） mRNA expression（F=7.648，29.83，25.08，all P＜0.05） and protein expression levels were up-regulated（F=12.42，10.88，14.32， all P＜0.05）. The mRNA expression levels of MMP-9 was downregulated（F=9.790，P＜0.01）.The mRNA expression of inflammatory factors IL-1α，MCP-1，and C1q in brain tissue were down-regulated（F=5.486，5.455，4.862，all P＜0.05）.In addition，AG490 treatment upregulated the expression of autophagy-related proteins LC3Ⅱ/LC3Ⅰ and Beclin-1（F=6.092，15.52，both P＜0.05），and downregulated the expression of P62 /SQSTM1（F=8.143，P＜0.05）. Conclusion：AG490 improves neurological dysfunction after ischemic stroke by inhibiting the pro-inflammatory effect of JAK2-STAT3 and regulating autophagy to reduce blood-brain barrier damage.

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备注/Memo

备注/Memo:

基金项目 国家自然科学基金 （82171320）
作者简介 张薇（1990-）女，硕士在读，研究方向：神经病学，
通信作者：阎涛，E-mail：taoyan@tmu.edu.cn。

常用功能

更新日期/Last Update: 2022-11-20