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低强度至中等强度耐力运动改善心肌梗死后大鼠的心脏功能与 Klotho 和 SIRT1 的正常化有关。

Improvement of Cardiac Function in Rats With Myocardial Infarction by Low-Intensity to Moderate-Intensity Endurance Exercise Is Associated With Normalization of Klotho and SIRT1.

机构信息

Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.

Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

J Cardiovasc Pharmacol. 2021 Jan 1;77(1):79-86. doi: 10.1097/FJC.0000000000000935.

Abstract

Exercise training (Ex) has beneficial effects on cardiovascular diseases by increasing Klotho and SIRT1. This study aimed to investigate whether the beneficial impact of Ex on myocardial infarction (MI) is mediated through Klotho and SIRT1. Fifty-six Wistar rats were divided into 4 main groups of Sham, MI, Ex, and MI + Ex. MI was induced by the closure of the left anterior descending. Animals were trained by endurance exercise for 4 weeks. In the end, hemodynamic and heart contractility indices were assessed. The levels of Klotho and SIRT1 in the serum and heart were measured by enzyme-linked immunosorbent assay and Western blot, respectively. The ADAM17 level in the heart and kidneys was assessed by enzyme-linked immunosorbent assay. The infarct size and fibrosis area were assessed by triphenyltetrazolium chloride and Masson trichrome staining, respectively. Ex recovered the reduction of dp/dt max and dp/dt min and decreased myocardial infarct size and fibrotic area in the MI group. Ex normalized the increase in heart rate, systolic blood pressure, left ventricular systolic pressure, and left ventricular end diastolic pressure in the MI group. Ex also normalized the reduction of the levels of Klotho and SIRT1 in serum and heart in the MI group. The changes of Klotho and SIRT1 in serum were positively correlated. Ex also restored ADAM17 levels in the MI group. Ex improved cardiac function in the MI group and is associated with reduction of the infarct size and normalization of Klotho and SIRT1 levels. Regarding unidirectional changes in Klotho and SIRT1, these proteins may play a role in beneficial effects of Ex on MI recovery.

摘要

运动训练(Ex)通过增加 Klotho 和 SIRT1 对心血管疾病有有益影响。本研究旨在探讨 Ex 对心肌梗死(MI)的有益影响是否通过 Klotho 和 SIRT1 介导。56 只 Wistar 大鼠分为 4 个主要组:Sham、MI、Ex 和 MI+Ex。通过左前降支闭塞诱导 MI。动物接受 4 周的耐力运动训练。最后,评估血流动力学和心脏收缩力指数。通过酶联免疫吸附试验和 Western blot 分别测量血清和心脏中的 Klotho 和 SIRT1 水平。通过酶联免疫吸附试验评估心脏和肾脏中的 ADAM17 水平。通过三苯基四氮唑氯化物和 Masson 三色染色评估梗塞面积和纤维化面积。Ex 恢复了 MI 组 dp/dt max 和 dp/dt min 的降低,并减少了心肌梗塞面积和纤维化面积。Ex 使 MI 组的心率、收缩压、左心室收缩压和左心室舒张末期压升高恢复正常。Ex 还使 MI 组血清和心脏中 Klotho 和 SIRT1 水平降低恢复正常。血清中 Klotho 和 SIRT1 的变化呈正相关。Ex 还恢复了 MI 组的 ADAM17 水平。Ex 改善了 MI 组的心脏功能,与梗塞面积减小和 Klotho 和 SIRT1 水平正常化有关。鉴于 Klotho 和 SIRT1 的单向变化,这些蛋白质可能在 Ex 对 MI 恢复的有益影响中发挥作用。

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