Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression
Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression
复制标题
DOI：
10.1038/sj.cr.7290184
复制
发表时间：
2003-10-01
期刊：
影响因子：
44.1
通讯作者：
Zhou, ZN
中科院分区：
文献类型：
--
作者：
Dong, JW;Zhu, HF;Zhou, ZN
间歇性缺氧已被证明可以提供心肌保护，防止缺血/再灌注诱导的损伤。在缺血/再灌注损伤中已经报道了通过凋亡引起的心肌细胞损失。本研究旨在探讨间歇性低氧是否能减轻缺血/再灌注诱导的心肌细胞凋亡及其可能机制。成年雄性SD大鼠在低压舱中模拟5000 in低氧暴露6 h/d，持续42 d。常氧组大鼠在常氧条件下饲养。两组离体灌流心脏进行30分钟的全脑缺血，然后再灌注60分钟。用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）和DNA琼脂糖凝胶电泳检测心肌细胞凋亡率。Western Blotting法检测凋亡相关蛋白Bax和Bcl-2在细胞浆和细胞膜中的表达。与常氧组相比，缺血再灌注后，间断低氧组心功能恢复明显加快。与常氧组相比，间歇性缺氧组缺血/再灌注诱导的细胞凋亡，如TUNEL阳性细胞核和DNA片段化所证明的，显著减少。与常氧组相比，缺血/再灌注后，间歇性低氧组心肌细胞浆和细胞膜Bax表达均减少。与常氧组相比，缺血/再灌注组胞浆Bcl-2表达水平无明显变化，但胞膜Bcl-2表达明显上调。这些结果表明，间歇性低氧对缺血/再灌注损伤的心脏保护作用似乎部分是由于减少心肌细胞凋亡。间歇性低氧通过增加Bcl-2/Bax比值，尤其是膜组分的比例，减轻缺血/再灌注诱导的细胞凋亡。
Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury. Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 in in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion. Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins, Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion, enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group. Ischemia/reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion, expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl-2/Bax, especially in membrane fraction.