Chronic intermittent hypobaric hypoxia protects the heart against ischemia/reperfusion injury through upregulation of antioxidant enzymes in adult guinea pigs  

作　　者：Hui-cai GUO Zhe ZHANG Li-nan ZHANG Chen XIONG Chen FENG Qian LIU Xu LIU Xiao-lu SHI Yong-li WANG 

机构地区：[1]Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China

出　　处：《Acta Pharmacologica Sinica》2009年第7期947-955,共9页中国药理学报（英文版）

基　　金：Acknowledgements This project was supported by the Natural Science Foundation of Hebei Province of China （No 301360）.

摘　　要：Aim： To investigate the protection and the anti-oxidative mechanism afforded by chronic intermittent hypobaric hypoxia （ClHH） against ischemia/reperfusion （I/R） injury in guinea pig hearts. Methods： Adult male guinea pigs were exposed to ClHH by mimicking a 5000 m high altitude （pB=404 mmHg, po2=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 ClHH 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 ClHH guinea pigs. Pretreatment of control hearts with an antioxidant mixture containing SOD and CAT exerted cardioprotective effects similar to ClHH. The irreversible CAT inhibitor aminotriazole （ATZ） abolished the cardioprotection of ClHH. 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.Aim： To investigate the protection and the anti-oxidative mechanism afforded by chronic intermittent hypobaric hypoxia （ClHH） against ischemia/reperfusion （I/R） injury in guinea pig hearts. Methods： Adult male guinea pigs were exposed to ClHH by mimicking a 5000 m high altitude （pB=404 mmHg, po2=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 ClHH 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 ClHH guinea pigs. Pretreatment of control hearts with an antioxidant mixture containing SOD and CAT exerted cardioprotective effects similar to ClHH. The irreversible CAT inhibitor aminotriazole （ATZ） abolished the cardioprotection of ClHH. 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.

关 键 词：chronic intermittent hypobaric hypoxia CARDIOPROTECTION antioxidant enzymes ISCHEMIA/REPERFUSION guinea pig 

分 类 号：Q463[生物学—生理学] Q945.78