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|本期目录/Table of Contents|

激活Notch信号途径对缺氧/复氧心肌细胞的保护作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2018年第5期
页码:
512-516
栏目:
基础研究
出版日期:
2018-06-25

文章信息/Info

Title:
Protective effects of Notch signaling pathway activation on hypoxia/reoxygenation cardiomyocytes
作者:
张荣怀1; 王凯燕2; 蔡维霞3; 万 卓4; 李 娟2; 张淑苗2; 郭海涛2; 王贵国5
（1.陕西省人民医院心血管内一科，陕西 西安 710068；第四军医大学：2.基础医学院生理与病理生理学教研室，3.西京医院烧伤与皮肤外科，4.唐都医院血液内科，陕西 西安 710032；5.中国人民解放军第174医院泌尿科，福建 厦门 361003）
Author(s):
ZHANG Rong-huai1;  WANG Kai-yan2;  CAI Wei-xia3;  WAN Zhuo4;  LI Juan2;  ZHANG Shu-miao2;  GUO Hai-tao2;  WANG Gui-guo5
(1.First Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi, China; 2.Department of Physiology and pathophysiology, 3.Department of Burns and Cutaneous Surgery, Xijing Hospital, Xi’an 710032, 4.Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi, 5.Department of Urinary Surgery, 174th Hospital of PLA. Xiamen 361003, Fujian, China)
关键词:
Notch; 活性氧簇; 缺氧/复氧; 细胞凋亡; 共培养
Keywords:
chronic neuropathic pain;  hypoxic pulmonary hypertension;  hypoxic pulmonary vasoconstriction;  aldehyde dehydrogenase 2
分类号:
R541.22文
DOI:
-
文献标识码:
A
摘要:
目的 观察激动Notch信号途径抗心肌细胞缺氧/复氧(hypoxia/reoxygenation,H/R)损伤的作用及其可能的机制。方法 将心肌细胞分为4组：常氧+OP9-GFP（OP9为稳转细胞系；GFP：green fluorescent protein为绿色荧光蛋白）组，常氧+OP9-Dll1（Dll1：Delta-like 1为Notch的配体）组，H/R+OP9-GFP组，H/R+OP9-Dll1组。用流式细胞仪检测心肌细胞凋亡，并应用荧光探针DCFH-DA检测细胞内活性氧簇（reactive oxygen species,ROS）水平的变化。结果 H/R后心肌细胞的凋亡水平增高（P<0.01）；与表达Dll1的OP9细胞系共培养，则可显著抑制心肌细胞的凋亡（P<0.01）；H/R增高的心肌细胞ROS水平（P<0.05，P<0.01）可以被共培养的OP9细胞系生成的Dll1显著降低（P<0.05，P<0.01）；应用百草枯可促进ROS的生成，而显著抑制Dll1激活心肌Notch信号途径的抗H/R凋亡效应（P<0.01）。结论 激活Notch信号途径，具有抗H/R后心肌损伤的作用，该作用可能与降低ROS水平有关。
Abstract:
AIM To observe the effect of stimulation of the Notch signaling pathway on apoptosis induced by myocardial hypoxia/reoxygenation (H/R). METHODS Cardiac myocytes were divided into four groups: Normoxia+OP9-GFP group (OP9, stable cell line; GFP, green fluorescent protein), Normoxia+OP9-Dll1 group (Dll1, Delta-like 1, Notch ligand), H/R+OP9-GFP group and H/R+OP9-Dll1 group. Apoptotic cells were observed by flow cytometry and intracellular reactive oxygen species (ROS) levels were assayed by fluorescence probe DCFH-DA. RESULTS The apoptotic cells significantly increased after hypoxia/reoxygenation (P<0.01). However, the apoptotic cells decreased when the cardiac myocytes were co-cultured with OP9-Dll1 (P<0.01), which produced Notch ligands. Intracellular ROS levels, which were significantly increased after hypoxia/reoxygenation (P<0.01), were reduced by co-cultured OP9-Dll (P<0.01). Paraquat used to increase intracellular ROS significantly inhibited anti-apoptotic effects of the Notch pathway after hypoxia/reoxygenation (P<0.01). CONCLUSION Activation of the Notch pathway after hypoxia/reoxygenation elicits anti-apoptotic effects on cardaic myocytes, which is related to decreased intracellular ROS levels.

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备注/Memo

备注/Memo:
收稿日期：2017-07-30.基金项目：国家自然科学基金项目资助（31100827），陕西省中医药科研项目资助（JCMS058），西安市科技计划项目资助（2017114SF/YX0088（8）），陕西省自然科学基金项目资助（13-ZY038），第四军医大学发展基金项目资助 （43411C005） 通讯作者：郭海涛，副教授，主要从事心血管生理学研究 Email：haitaoguo@fmmu.edu.cn 共同通讯作者：王贵国，副主任医师，主要从事心肾疾病研究 Email：15359885667@163.com 作者简介：张荣怀，副主任医师，博士 Email：zrh-rr@163.com
更新日期/Last Update: 1900-01-01