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轴突导向因子 1 在中等强度运动对大鼠心肌纤维化的作用中发挥作用。

Netrin-1 plays a role in the effect of moderate exercise on myocardial fibrosis in rats.

机构信息

Department of Cardiology, First Hospital of Harbin City, Harbin, Heilongjiang Province, China.

Clinical Pharmacy, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China.

出版信息

PLoS One. 2019 Feb 21;14(2):e0199802. doi: 10.1371/journal.pone.0199802. eCollection 2019.

DOI:10.1371/journal.pone.0199802
PMID:30789913
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6383912/
Abstract

INTRODUCTION

This study aimed to investigate the effect of aerobic exercise on the expression of neitrin-1,DCC receptor and myocardial fibrosis in rats with acute myocardial infarction.

METHODS

Twenty-four rats were randomly divided into three groups: the sham group (n = 8), the acute myocardial infarction (AMI) model group (n = 8), and the aerobic exercise treatment after acute myocardial infarction group (ET) (n = 8). After 10 weeks, the serum levels of netrin-1, tumor necrosis factor alpha α (TNF-α), and interleukin 6 (IL-6) were measured. The expression of matrix metalloproteinase 2 and 9 (MMP2, 9), and their inhibitor, tissue inhibitor of metalloproteinase 2 (TIMP2), myocardial netrin-1, and the deleted in colorectal cancer (DCC) receptor were evaluated. Histopathological results were also evaluated. The collagen volume fraction of the myocardial tissues was also calculated.

RESULTS

Compared with the sham group, in the AMI and ET groups, left ventricular end diastolic pressure (LVEDP) were increased, while left ventricular systolic pressure (LVSP), and left ventricular pressure maximal rate of rise and fall (± dp/dtmax) were significantly decreased (P<0.05,). Compared with the AMI group, in the ET group, LVSP, and ±dp/dtmax were significantly increased while LVEDP was decreased (P<0.05). Compared with the sham group, the AMI group and ET groups showed increased levels of serum TNF-α, IL-6 and significantly reduced levels of netrin-1. Levels of TNF-α and IL-6 were significantly reduced in the ET group compared with the AMI group, whereas the level of netrin-1 was increased. The expression of myocardial MMP2 and MMP9 was significantly increased in the AMI group compared with the sham group, whereas that of myocardial netrin-1, TIMP2 and the DCC receptor, was significantly reduced. Compared with the AMI group, the ET group showed reduced expression of myocardial MMP2 and MMP9 proteins, whereas expression of myocardial netrin-1, TIMP2 and the DCC receptor, was significantly increased. The collagen volume fraction of the myocardial tissues was significantly increased in the AMI group and the ET group compared with the sham group, with a greater increase in the AMI group.

CONCLUSIONS

Aerobic exercise increased levels of serum netrin-1, myocardial netrin-1, and the DCC receptor and reduced the expression of myocardial MMP2 and MMP9 proteins, to improve the degree of fibrosis following myocardial infarction in rats.

摘要

简介

本研究旨在探讨有氧运动对急性心肌梗死大鼠神经纤毛蛋白 1(neitrin-1)、DCC 受体表达及心肌纤维化的影响。

方法

将 24 只大鼠随机分为三组:假手术组(n = 8)、急性心肌梗死(AMI)模型组(n = 8)和急性心肌梗死后有氧运动治疗组(ET)(n = 8)。10 周后,检测血清神经纤毛蛋白 1、肿瘤坏死因子-α(TNF-α)和白细胞介素 6(IL-6)水平。评估基质金属蛋白酶 2 和 9(MMP2、9)及其抑制剂组织金属蛋白酶抑制剂 2(TIMP2)、心肌神经纤毛蛋白 1 和结直肠癌缺失基因(DCC)受体的表达。还评估了组织病理学结果。计算心肌组织胶原容积分数。

结果

与假手术组相比,AMI 组和 ET 组左心室舒张末期压(LVEDP)升高,左心室收缩压(LVSP)和左心室压力最大上升和下降速率(±dp/dtmax)显著降低(P<0.05)。与 AMI 组相比,ET 组 LVSP 和±dp/dtmax 显著升高,LVEDP 降低(P<0.05)。与假手术组相比,AMI 组和 ET 组血清 TNF-α、IL-6 水平升高,神经纤毛蛋白 1 水平降低。与 AMI 组相比,ET 组 TNF-α 和 IL-6 水平降低,神经纤毛蛋白 1 水平升高。与假手术组相比,AMI 组心肌 MMP2 和 MMP9 表达明显增加,而心肌神经纤毛蛋白 1、TIMP2 和 DCC 受体表达明显减少。与 AMI 组相比,ET 组心肌 MMP2 和 MMP9 蛋白表达减少,而心肌神经纤毛蛋白 1、TIMP2 和 DCC 受体表达明显增加。与假手术组相比,AMI 组和 ET 组心肌组织胶原容积分数明显增加,AMI 组增加更明显。

结论

有氧运动增加血清神经纤毛蛋白 1、心肌神经纤毛蛋白 1 和 DCC 受体水平,减少心肌 MMP2 和 MMP9 蛋白表达,改善大鼠心肌梗死后纤维化程度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbce/6383912/b6c2a89e2297/pone.0199802.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbce/6383912/00e2877e575e/pone.0199802.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbce/6383912/cef855c30143/pone.0199802.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbce/6383912/b6c2a89e2297/pone.0199802.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbce/6383912/00e2877e575e/pone.0199802.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbce/6383912/731088f1fdce/pone.0199802.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbce/6383912/dbfba66fad1c/pone.0199802.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbce/6383912/cef855c30143/pone.0199802.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbce/6383912/b6c2a89e2297/pone.0199802.g005.jpg

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