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|本期目录/Table of Contents|

激活Notch1通路减轻高温高湿条件下H9C2心肌细胞缺氧/复氧损伤

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2017年第5期
页码:
512-517
栏目:
基础研究
出版日期:
2017-03-25

文章信息/Info

Title:
Activation of Notch1 pathway alleviates hypoxia/reoxygenation injury of H9C2 cardiomyocytes in high temperature and humidity
作者:
吕 平; 李 巍; 杨亚丽; 吴 萌; 胡建华; 纪兆乐; 尹志勇; 李 妍
（第四军医大学西京医院心血管内科，陕西 西安 710032）
Author(s):
L? Ping;  LI Wei;  YANG Ya-li;  WU Meng;  HU Jian-hua;  JI Zhao-le;  YIN Zhi-yong;  LI Yan
(Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
Notch1; 自噬; 缺氧/复氧损伤; 高温高湿
Keywords:
Notch1;  autophagy;  hypoxia/reoxygenation injury;  high temperature and humidity
分类号:
R392.3
DOI:
-
文献标识码:
A
摘要:
目的 明确Notch1通路在高温高湿条件下H9C2心肌细胞缺氧/复氧(Hypoxia/Reoxygenation,H/R)损伤中的作用及其潜在机制。方法 常规培养H9C2心肌细胞并将其分6组即对照组；H/R组；高温高湿组；高温高湿+H/R组；高温高湿+Jagged1（Notch1激动剂）+H/R组；高温高湿+溶剂+H/R组。TUNEL法检测细胞凋亡，荧光探针JC-1检测线粒体膜电位，ATP检测试剂盒检测ATP含量，Western blot检测Notch1细胞内段（Notch1 intracellular domain，Notch1 ICD）、Hairy和分裂增强子（Hairy and enhancer of split，Hes1）、微管相关蛋白1轻链3（microtubule-associated protein1 light chain 3，LC3）和p62的蛋白表达水平。结果 与对照组相比，急性损伤H/R后，细胞凋亡增加（P<0.05），线粒体膜电位降低（P<0.05），ATP含量减少（P<0.05），Notch1 ICD、Hes1、LC3-II/I（p62相应降低）表达升高（P<0.05），而慢性损伤高温高湿后，细胞凋亡增加（P<0.05），线粒体膜电位降低（P<0.05），ATP含量减少（P<0.05），Notch1 ICD、Hes1、LC3-II/I表达降低（p62相应升高）（P<0.05）；和H/R组或高温高湿组对比，高温高湿+H/R组中细胞凋亡进一步增加（P<0.05），线粒体膜电位和ATP含量进一步降低（P<0.05），Notch1 ICD、Hes1、LC3-II/I表达进一步降低（p62进一步升高）（P<0.05）；和高温高湿+H/R组对比，加入Notch1激动剂Jagged1后，细胞凋亡减少（P<0.05），线粒体膜电位和ATP含量增高（P<0.05），Notch1 ICD、Hes1、LC3-II/I表达升高（p62相应降低）（P<0.05）。结论 激活Notch1通路通过促进自噬从而缓解高温高湿条件下H9C2心肌细胞缺氧/复氧损伤。
Abstract:
AIM To investigate the role of Notch1 pathway and its underlying mechanisms in H9C2 cardiomyocytes subjected to hypoxia/reoxygenation (H/R) injury in high temperature and humidity. METHODS H9C2 cardiomyocytes were cultured and divided into six groups: control group, H/R group, high temperature and humidity group, high temperature and humidity+H/R group, high temperature and humidity+Jagged1 (an activator of Notch1)+H/R group and high temperature and humidity+vehicle+H/R group. Cell apoptosis was detected by TUNEL, mitochondrial membrane potential was assessed by JC-1 and ATP content was measured by an ATP bioluminescent assay kit. The expression of Notch1 intracellular domain (Notch1 ICD), Hairy and enhancer of split (Hes1), microtubule-associated protein1 light chain 3 (LC3) and p62 were analyzed by Western blot. RESULTS Compared with those in control group, H/R injury significantly increased cell apoptosis index (P<0.05), reduced mitochondrial membrane potential (P<0.05) and ATP content (P<0.05), and increased expressions of Notch1 ICD, Hes1 and LC3-II/I (except p62) (P<0.05). Although high temperature and humidity also increased cell apoptosis index (P<0.05), reduced mitochondrial membrane potential (P<0.05) and ATP content (P<0.05), it reduced expressions of Notch1 ICD, Hes1 and LC3-II/I (except p62) (P<0.05) compared with those in control group. In addition, compared with those in H/R group or high temperature and humidity group, cell apoptosis index further increased (P<0.05), mitochondrial membrane potential (P<0.05) and ATP content reduced (P<0.05), and the expressions of Notch1 ICD, Hes1 and LC3-II/I(except p62) decreased (P<0.05) in high temperature and humidity+H/R group. Moreover, compared with those in high temperature and humidity+H/R group, adding Jagged1 (an activator of Notch1) reduced cell apoptosis index (P<0.05) and increased the mitochondrial membrane potential (P<0.05) and ATP content (P<0.05) as well as the expressions of Notch1 ICD, Hes1 and LC3-II/I (except p62) (P<0.05). CONCLUSION Activation of Notch1 pathway can alleviate hypoxia/reoxygenation injury of H9C2 cardiomyocytes in high temperature and humidity through accelerating autophagy.

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备注/Memo

备注/Memo:
收稿日期：2016-10-11.
基金项目：全军后勤科研项目资助（CWS14J065）；国家自然科学基金项目资助（81570252；81500195）
通讯作者：李妍，副教授，主要从事冠心病基础和临床研究 Email：liyanfmmu@hotmail.com 共同
通讯作者：尹志勇，讲师，博士，主要从事缺血性心脏病损伤与保护研究 Email：zhiyong_yin@163.com
作者简介：吕平，硕士生 Email：2383067104@qq.com 共同第一作者：李巍，硕士生 Email：364573149@qq.com
更新日期/Last Update: 2017-04-20