Department of Geriatrics, The First Affiliated Hospital, Third Military Medical University, Chongqing, China.
Ups J Med Sci. 2013 May;118(2):65-74. doi: 10.3109/03009734.2013.766914. Epub 2013 Feb 26.
This study investigated the effects of short-term intermittent hypoxia (IH) preconditioning on cardiac structure and function in rats and the influence of ischemia reperfusion (I/R) injury. Special attention was then paid to the involvement of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF).
Wistar rats were given IH treatment for 1, 7, 14, or 28 days. Some of them were thereafter subject to myocardial infarction surgery. Right ventricle systolic pressure (RVSP), myocardial capillary density (CD), and mRNA/protein expression of HIF-1α, VEGF, and Bcl-2 in rat myocardial tissue were determined. Apoptotic cell number was determined by TUNEL staining, and concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured.
IH treatment for 1, 7, 14, and 28 days reduced the myocardial infarction size, whereas IH for 28 days increased the RVSP, ratio of right to left ventricle weight (RV/LV+S), and CD. IH up-regulated the mRNA and protein levels of HIF-1α, VEGF, and Bcl-2 both under normal and I/R conditions. The induced expression of HIF-1α and VEGF by IH reached a peak after 7 days of treatment. Moreover, IH for 28 days induced cardiomyocyte apoptosis, whereas prior treatment with IH for 1, 7, 14, and 28 days all markedly attenuated the apoptosis effected by the subsequent I/R injury. IH also decreased the concentrations of MDA but increased those of SOD in myocardial tissue of both in normal rats and following I/R.
The present study demonstrates that short-term IH protects the heart from I/R injury through inhibiting apoptosis and oxidative stress. The up-regulation of HIF-1α and VEGF by short-term IH may participate in the cardioprotective effect of IH.
本研究旨在探讨短期间歇性低氧（IH）预处理对大鼠心脏结构和功能的影响及其对缺血再灌注（I/R）损伤的影响。特别关注缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）的作用。
给予 Wistar 大鼠 1、7、14 或 28 天的 IH 处理。其中一些大鼠随后接受心肌梗死手术。测定右心室收缩压（RVSP）、心肌毛细血管密度（CD）以及大鼠心肌组织中 HIF-1α、VEGF 和 Bcl-2 的 mRNA/蛋白表达。通过 TUNEL 染色测定凋亡细胞数，并测定丙二醛（MDA）和超氧化物歧化酶（SOD）的浓度。
1、7、14 和 28 天的 IH 处理减少了心肌梗死面积，而 28 天的 IH 处理增加了 RVSP、右室与左室加室间隔重量比（RV/LV+S）和 CD。IH 在正常和 I/R 条件下均上调 HIF-1α、VEGF 和 Bcl-2 的 mRNA 和蛋白水平。IH 诱导的 HIF-1α和 VEGF 表达在治疗 7 天后达到高峰。此外，28 天的 IH 诱导心肌细胞凋亡，而 1、7、14 和 28 天的 IH 预处理均显著减轻随后的 I/R 损伤引起的凋亡。IH 还降低了心肌组织中 MDA 的浓度，但增加了 SOD 的浓度，无论是在正常大鼠还是在 I/R 后。
本研究表明，短期 IH 通过抑制细胞凋亡和氧化应激来保护心脏免受 I/R 损伤。短期 IH 上调 HIF-1α 和 VEGF 可能参与 IH 的心脏保护作用。
