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强力霉素降低 和去卵巢小鼠主动脉粥样硬化病变与基质金属蛋白酶-2 活性降低相关。

Doxycycline Decreases Atherosclerotic Lesions in the Aorta of and Ovariectomized Mice with Correlation to Reduced MMP-2 Activity.

机构信息

Institute of Biological Sciences, Federal University of Pará, Cardiovascular System Pharmacology and Toxicology Laboratory, Belém 66075-110, PA, Brazil.

Department of Biomechanics, Medicine and Locomotor Apparatus Rehabilitation, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, Ribeirão Preto 14049-900, SP, Brazil.

出版信息

Int J Mol Sci. 2022 Feb 25;23(5):2532. doi: 10.3390/ijms23052532.

DOI:10.3390/ijms23052532
PMID:35269673
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8910467/
Abstract

Atherogenic events promote changes in vessel walls, with alteration of the redox state, and increased activity of matrix metalloproteinases (MMPs). Thus, this study aims to evaluate aortic remodeling, MMP activity, and reactive oxygen species (ROS) levels after treatment with doxycycline in ApoE-⁄- and ovariectomized mice (OVX). Female ApoE-⁄--knockout mice (5 weeks) were submitted to ovariectomy surgery to induce experimental menopause. They then received chow enriched with 1% cholesterol to induce hypercholesterolemia. The animals were divided into two experimental groups: ApoE-⁄-/OVX vehicle and ApoE-⁄-/OVX doxycycline (30 mg/kg) administered by gavage once a day for 28 days (15th to the 18th week of life). Blood samples were collected to measure total cholesterol and fractions. The aorta was used for morphometry and to measure the activity and expression of MMP-2 and ROS levels. The ApoE-⁄-/OVX doxycycline group showed no change in total and fraction cholesterol levels. However, there was a reduction in ROS levels, MMP-2 expression, and activity that correlated with a decrease in atherosclerotic lesions relative to the ApoE-⁄-/OVX vehicle (p > 0.05). Therefore, we conclude that doxycycline in ApoE-⁄-/OVX animals promotes a reduction in atherosclerotic lesions by reducing ROS and MMP-2 activity and expression.

摘要

动脉粥样硬化事件会导致血管壁发生变化，氧化还原状态发生改变，基质金属蛋白酶（MMPs）活性增加。因此，本研究旨在评估载脂蛋白 E 基因敲除（ApoE-/-）和去卵巢（OVX）小鼠经强力霉素治疗后的主动脉重塑、MMP 活性和活性氧（ROS）水平。雌性 ApoE-/-基因敲除小鼠（5 周龄）接受卵巢切除术以诱导实验性绝经。然后，它们接受富含 1%胆固醇的饲料以诱导高胆固醇血症。动物分为两组：ApoE-/-/OVX 载体和 ApoE-/-/OVX 强力霉素（30mg/kg），通过灌胃每天给药一次，共 28 天（生命的第 15 周到第 18 周）。采集血样以测量总胆固醇和各组分。取主动脉进行形态计量学测量，并测量 MMP-2 的活性和表达以及 ROS 水平。与 ApoE-/-/OVX 载体相比，ApoE-/-/OVX 强力霉素组的总胆固醇和各组分胆固醇水平没有变化。然而，ROS 水平、MMP-2 表达和活性降低，与动脉粥样硬化病变减少相关（p＞0.05）。因此，我们得出结论，强力霉素在 ApoE-/-/OVX 动物中通过降低 ROS 和 MMP-2 活性和表达来促进动脉粥样硬化病变的减少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a9e/8910467/b4e5595c23d3/ijms-23-02532-g006.jpg
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