Chronic intermittent hypobaric hypoxia protects the heart against ischemia/reperfusion injury through upregulation of antioxidant enzymes in adult guinea pigs
Chronic intermittent hypobaric hypoxia protects the heart against ischemia/reperfusion injury through upregulation of antioxidant enzymes in adult guinea pigs
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DOI：
10.1038/aps.2009.57
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发表时间：
2009-07-01
影响因子：
8.2
通讯作者：
Wang, Yong-li
中科院分区：
文献类型：
--
作者：
Guo, Hui-cai;Zhang, Zhe;Wang, Yong-li
目的：探讨慢性间歇性低压低氧(CIHH)对豚鼠心脏缺血/再灌注(I/R)损伤的保护作用及其抗氧化机制。方法：成年雄性豚鼠模拟海拔5000 m高原(p(B)=404 mm Hg，p(02)=84 mm Hg)，在低压舱中暴露6h/d，共28天。采用Langendorff灌流的豚鼠离体心，测定基础灌注期、缺血期和再灌注期的左心功能指标。采用生化法和Western blotting法分别检测左心肌抗氧化酶活性和蛋白表达。结果：CIHH豚鼠心肌缺血30min，再灌流60min后，心功能恢复率明显高于对照组。CIHH豚鼠心肌超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性和蛋白表达均显著增加。用含超氧化物歧化酶和过氧化氢酶的抗氧化剂混合物对对照心脏进行预处理，其心脏保护作用与CIHH相似。不可逆CAT抑制剂氨基三氮唑(ATZ)可阻断CIHH的心脏保护作用。CIHH和CAT可减轻外源性过氧化氢(H_2O_2)所致的心脏收缩功能障碍和氧化应激反应。结论：CIHH通过上调抗氧化酶对豚鼠心脏I/R损伤具有保护作用。
Aim: To investigate the protection and the anti-oxidative mechanism afforded by chronic intermittent hypobaric hypoxia (CIHH) against ischemia/reperfusion (I/R) injury in guinea pig hearts.Methods: Adult male guinea pigs were exposed to CIHH by mimicking a 5000 m high altitude (p(B)=404 mmHg, p(02)=84 mmHg) in a hypobaric chamber for 6 h/day for 28 days. Langendorff-perfused isolated guinea pig hearts were used to measure variables of left ventricular function during baseline perfusion, ischemia and the reperfusion period. The activity and protein expression of antioxidant enzymes in the left myocardium were evaluated using biochemical methods and Western blotting, respectively. Intracellular reactive oxygen species (ROS) were assessed using ROS-sensitive fluorescence.Results: After 30 min of global no-flow ischemia followed by 60 min of reperfusion, myocardial function had better recovery rates in CIHH guinea pig hearts than in control hearts. The activity and protein expression of superoxide dismutase (SOD) and catalase (CAT) were significantly increased in the myocardium of CIHH guinea pigs. Pretreatment of control hearts with an antioxidant mixture containing SOD and CAT exerted cardioprotective effects similar to CIHH. The irreversible CAT inhibitor aminotriazole (ATZ) abolished the cardioprotection of CIHH. Cardiac contractile dysfunction and oxidative stress induced by exogenous hydrogen peroxide (H2O2) were attenuated by CIHH and CAT.Conclusions: These data suggest that CIHH protects the heart against I/R injury through upregulation of antioxidant enzymes in guinea pig.