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

卷:

30卷

期数:

2024年04期

页码:

350-355

栏目:

基础医学

出版日期:

2024-07-10

文章信息/Info

Title:

Intermittent hypoxia improves cardiac function recovery after myocardial infarction in mice via MEK/ERK signaling

文章编号:

1006-8147(2024)044-0350-06

作者:

丁心语; 王俊懿; 黄传; 万春晓

（天津医科大学总医院康复科，天津300052）

Author(s):

DING Xinyu; WANG Junyi; HUANG Chuan; WAN Chunxiao

（Department of Physical Medicine and Rehabilitation，Tianjin Medical University General Hospital，Tianjin 300052，China）

关键词:

心肌梗死; 间歇性低氧; 细胞凋亡; 丝裂原活化蛋白激酶; 细胞外信号调节激酶

Keywords:

myocardial infarction;  intermittent hypoxia;  apoptosis;  mitogen-activated protein kinase;  extracellular signal-regulated kinase

分类号:

R54

DOI:

10.20135/j.issn.1006-8147.2024.04.0350

文献标志码:

A

摘要:

目的：研究间歇性低氧（IH）对心肌梗死（MI）后C57BL/6小鼠心脏功能的影响及其机制。方法：将24只小鼠随机划分为4 组：假手术组（SHAM，n=6）、假手术低氧组（SHAM-IH，n=6）、心肌梗死组（MI，n=6）和心肌梗死低氧组（MI-IH，n=6）。超声心动检测小鼠左心室射血分数（LVEF）和左心室缩短分数（LVFS）。Masson染色检测心肌纤维化程度。Tunel染色检测细胞凋亡。蛋白印迹检测丝裂原活化蛋白激酶激酶（MEK）蛋白及其磷酸化、细胞外信号调节激酶1/2（ERK1/2）蛋白及其磷酸化和裂解半胱氨酸蛋白酶3（cleaved caspase 3）蛋白的水平。体外实验用H2O2诱导H9C2细胞损伤以模拟氧化应激，加入MEK/ERK抑制剂（U0126），检测MEK和ERK1/2的蛋白及其磷酸化水平、cleaved caspase 3蛋白水平。结果：（1）干预4周后，与MI组相比，MI-IH组 LVEF、LVFS明显增加（t=-15.520、-15.080，均P＜0.001），心肌纤维化减少（t=9.547，P＜0.05），MEK、ERK1/2的磷酸化、cleaved caspase 3水平均减少（t=2.292、3.267、6.399，均P＜0.05），细胞凋亡减少（t=4.341，P＜0.001）。（2）与H2O2组相比，H2O2+U0126组MEK、ERK1/2的磷酸化减少，caspase 3活化降低（t=3.599、9.692、6.607，均P＜0.05）。结论：IH通过MEK/ERK信号抑制心肌细胞凋亡，从而促进MI小鼠心功能的恢复。

Abstract:

Objective： To explore the effects and mechanisms of intermittent hypoxia（IH） on the cardiac functionin C57BL/6 mice after myocardial infarction（MI）. Methods：Twenty-four mice were classified randomly into four groups： sham group（SHAM，6 mice），sham operation with IH treatment group（SHAM-IH，6 mice），myocardial infarction group（MI，6 mice） and myocardial infarction with IH treatment group（MI，6 mice）. Echocardiography was used to detect left ventricular ejection fraction（LVEF） and left ventricular shortening fraction（LVFS） in mice. Masson staining was used to detect the degree myocardial fibrosis. Tunel staining was used to detect cardiomyocytes apoptosis. Protein immunoblotting was performed to detect mitogen-activated protein kinase kinase（MEK） protein and its phosphorylation（p-MEK） level，extracellular signal-regulated kinase 1/2（ERK1/2） protein and its phosphorylation（p-ERK1/2）level，and cleaved cysteine protease 3（cleaved caspase 3） protein level. In vitro experiments，H9C2 cells were induced with H2O2 tomimic oxidative stress，MEK，ERK1/2，p-MEK，p-ERK1/2，and cleaved caspase 3 protein levels were detected after treated with MEK/ERK inhibitor（U0126）. Results：After 4 weeks of intervention，compared with the MI group，LVEF and LVFS were significantly increased（t=-15.520，-15.080，both P＜0.001），myocardial fibrosis（t=9.547，P＜0.05），p-MEK，p-ERK1/2 expression and cleaved caspase 3（t=2.292，3.267，6.399，all P＜0.05）and Tunel-positive cells（t=4.341，P＜0.001）were significantly decreased in the MI-IH group.Compared to the H2O2 group，the H2O2+U0126 group had decreased protein levels of p-MEK，p-ERK1/2 and cleaved caspase 3（t=3.599，9.692，6.607，all P＜0.05）. Conclusion：IH intervention inhibits cardiomyocyte apoptosis through MEK/ERK signaling，thereby improving the recovery of cardiac function in mice after myocardial infarction.

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备注/Memo

备注/Memo:

基金项目：天津市医学重点学科（专科）建设项目（TJYXZDXK-060B）；天津市卫健委科技项目青年项目（TJWJ2023QN008）
作者简介：丁心语（1999-），女，硕士在读，研究方向：心脏康复研究；
通信作者：万春晓，E-mail：cwan@tmu.edu.cn。

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更新日期/Last Update: 2024-07-10