High-altitude chronic hypoxia prevents myocardial dysfunction in experimental model of type 2 diabetes.

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yixuan Wan, Lisha Zhang, Lei Wang, Yu Zhang, FaBao Gao
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引用次数: 0

Abstract

Background: High-altitude chronic hypoxia (CHH) has a favorable impact on the lower prevalence of diabetes together with the better glucose tolerance. However, whether it prevents diabetic cardiomyopathy remains unclear. This study aimed to investigate the effects of CHH on left ventricular (LV) function in experimental model of type 2 diabetes.

Methods: Sprague-Dawley rats were randomly divided into control (altitude 500 m), DM (diabetes mellitus and altitude 500 m), CHH (altitude 4250 m and non-diabetic for 2 weeks), CHH-DM2 (altitude 4250 m and DM for 2 weeks), and CHH-DM8 (altitude 4250 m and DM for 8 weeks) groups. The experimental model of type 2 diabetes was induced by a high-fat diet plus low-dose streptozotocin (35mg/kg, intraperitoneal) after fasted overnight. Left ventricular cardiac function and global myocardial strain were evaluated at 2, and 8 weeks by 7.0 T cardiovascular magnetic resonance. Subsequently, biochemical indices, histological evaluation, and levels of hypoxia-induced factor (HIF)-1α were assessed.

Results: Left ventricular ejection fraction (LVEF), global longitudinal (GLS), circumferential (GCS), and radial (GRS) strains significantly decreased in the DM group compared with the controls. However, these abnormalities in DM rats were significantly prevented in the CHH-DM2 group, and were further improved in CHH-DM8 group. Mechanistically, prolonged CHH at high altitude further reduced cardiac apoptosis, and oxidative stress, and increased autophagy, and the expression of HIF-1α in diabetic myocardial tissue.

Conclusions: CHH exerted cardioprotective effects by improving LV function, increasing myocardial strain and attenuating cardiac hypertrophy in type 2 diabetic rats, likely through reducing apoptosis and oxidative stress, activating autophagy and HIF-1α signaling in diabetic rats.

背景:高海拔慢性缺氧(CHH)对降低糖尿病发病率和改善葡萄糖耐量有积极影响。然而,它是否能预防糖尿病心肌病仍不清楚。本研究旨在探讨高海拔对 2 型糖尿病实验模型左心室功能的影响:将 Sprague-Dawley 大鼠随机分为对照组(海拔 500 米)、DM 组(糖尿病和海拔 500 米)、CHH 组(海拔 4250 米和非糖尿病 2 周)、CHH-DM2 组(海拔 4250 米和 DM 2 周)和 CHH-DM8 组(海拔 4250 米和 DM 8 周)。2 型糖尿病的实验模型是通过高脂饮食加小剂量链脲佐菌素(35 毫克/千克,腹腔注射)诱导的。通过 7.0 T 心血管磁共振在 2 周和 8 周时评估左心室心功能和整体心肌应变。随后,对生化指标、组织学评价和缺氧诱导因子(HIF)-1α的水平进行了评估:结果:与对照组相比,DM 组的左心室射血分数(LVEF)、整体纵向(GLS)、周向(GCS)和径向(GRS)应变显著下降。然而,CHH-DM2 组能明显防止 DM 大鼠的这些异常,CHH-DM8 组则得到进一步改善。从机理上讲,长期高海拔CHH可进一步减少糖尿病心肌组织中的心脏凋亡和氧化应激,增加自噬和HIF-1α的表达:CHH通过改善2型糖尿病大鼠的左心室功能、增加心肌应变和减轻心肌肥厚发挥了心脏保护作用,这可能是通过减少糖尿病大鼠的细胞凋亡和氧化应激、激活自噬和HIF-1α信号传导实现的。
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来源期刊
Archives of biochemistry and biophysics
Archives of biochemistry and biophysics 生物-生化与分子生物学
CiteScore
7.40
自引率
0.00%
发文量
245
审稿时长
26 days
期刊介绍: Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics. Research Areas Include: • Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing • Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions • Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.
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