Hypoxia-inducible factor-1α and vascular endothelial growth factor in the cardioprotective effects of intermittent hypoxia in rats.
Hypoxia-inducible factor-1α and vascular endothelial growth factor in the cardioprotective effects of intermittent hypoxia in rats.
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DOI：
10.3109/03009734.2013.766914
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发表时间：
2013-05
影响因子：
3.4
通讯作者：
Si LY
中科院分区：
文献类型：
--
作者：
Wang Z;Si LY
本研究观察了短时间歇低氧(IH)预适应对大鼠心脏结构和功能的影响及对缺血再灌注(I/R)损伤的影响。然后特别注意低氧诱导因子-1α(HIF-1α)和血管内皮生长因子的参与。Wistar大鼠分别给予1d、7d、14d、28d的IH治疗。他们中的一些人后来接受了心肌梗死手术。测定大鼠右室收缩压、心肌毛细血管密度及心肌组织中缺氧诱导因子-1α、血管内皮生长因子和Bcl2的基因和蛋白表达。TUNEL法检测细胞凋亡率，丙二醛(MDA)、超氧化物歧化酶(SOD)含量测定。IH治疗1、7、14、28d后，心肌梗死范围缩小，而Ih治疗28d后，右室压、右室与左室重量比(RV/LV+S)和Cd增加。在正常和I/R条件下，缺氧诱导因子-1α、血管内皮生长因子和Bcl2的基因和蛋白表达均上调。IH诱导的缺氧诱导因子-1α和血管内皮生长因子的表达在治疗后7d达到高峰。此外，IH治疗28天可诱导心肌细胞凋亡，而IH治疗1、7、14和28天均可显著减弱随后的I/R损伤所引起的心肌细胞凋亡。Ih还能降低正常大鼠和I/R大鼠心肌组织中丙二醛的含量，升高心肌组织中的超氧化物歧化酶的含量。本研究表明，短期的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上调缺氧诱导因子-1α和血管内皮生长因子可能参与了IH的心脏保护作用。
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.