Guo Hui-Cai, Zhang Zhe, Zhang Li-Nan, Xiong Chen, Feng Chen, Liu Qian, Liu Xu, Shi Xiao-Lu, Wang Yong-Li
Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
Acta Pharmacol Sin. 2009 Jul;30(7):947-55. doi: 10.1038/aps.2009.57. Epub 2009 Jun 22.
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.
Adult male guinea pigs were exposed to CIHH by mimicking a 5000 m high altitude (p(B)=404 mmHg, p(O2)=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.
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 (H(2)O(2)) were attenuated by CIHH and CAT.
These data suggest that CIHH protects the heart against I/R injury through upregulation of antioxidant enzymes in guinea pig.Acta Pharmacologica Sinica (2009) 30: 947-955; doi: 10.1038/aps.2009.57; published online 22 June 2009.
研究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。
成年雄性豚鼠在低压舱中模拟5000米高空（p(B)=404 mmHg，p(O2)=84 mmHg），每天暴露于CIHH环境6小时，持续28天。采用Langendorff灌流的离体豚鼠心脏，测量基础灌流、缺血及再灌注期间左心室功能的各项指标。分别采用生化方法和蛋白质免疫印迹法评估左心室心肌中抗氧化酶的活性和蛋白表达。利用对活性氧敏感的荧光法评估细胞内活性氧（ROS）水平。
经历30分钟全心无血流缺血及60分钟再灌注后，CIHH豚鼠心脏的心肌功能恢复率优于对照心脏。CIHH豚鼠心肌中超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性及蛋白表达显著增加。用含SOD和CAT的抗氧化剂混合物预处理对照心脏，可产生与CIHH相似的心脏保护作用。不可逆的CAT抑制剂氨基三唑（ATZ）可消除CIHH的心脏保护作用。CIHH和CAT可减轻外源性过氧化氢（H(2)O(2)）诱导的心脏收缩功能障碍和氧化应激。
这些数据表明，CIHH通过上调豚鼠心脏中的抗氧化酶来保护心脏免受I/R损伤。《中国药理学报》（2009年）30卷：947 - 955页；doi: 10.1038/aps.2009.57；2009年6月22日在线发表。
