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作 者:钟宁 张翼[1] 朱海峰[1] 王军臣 方奇志 周兆年
机构地区:[1]中国科学院上海生命科学院健康科学中心,上海200031 [2]上海东方医院病理科,上海中国200057
出 处:《Acta Pharmacologica Sinica》2002年第4期305-310,共6页中国药理学报(英文版)
基 金:Project supported by the National Natural Sciences Foundation of China, № 39500052.
摘 要:AIM: To determine the effects of simulated intermittent high altitude hypoxia adaptation ( HA) on coronary capillary and coronary flow (CF) in rat hearts. METHODS: Model of Langendorf-perfused isolated rat hearts were used to measure CF during ischemia-reperfusion, and immunoperoxidase staining assay and computer-aid morphometry analysis were conducted to determine the myocardial capillary densities. Cyclic GMP (cGMP) level in myocardium was measured by radio-immunoassay. RESULTS: Pre-ischemia level of CF in MA rats was higher (IHA28 13.4 mL/min±1.5 mL/min, IHA42 15.4 mL/min ±2.0 mL/min, P < 0.01) than that of normoxic rats (11.0±0.8) mL/min, and the recovery of CF after ischemia-reperfusion was better in MA rats. As an adaptive result, the myocardial capillary densities of the left ventricular myocardium in IHA rats were 1.5 times of those in normoxic control rats, but there was no apparent ventricular hypertrophy in IHA rats. Myocardial cGMP content (1.8±0.7) nmol/ g in IHA rats were increased significantly compared with control rats (1.1±0.4) nmol/g, but cGMP level was not altered before and after ischemia-reperfusion in either group. It was also revealed that in isolated rat hearts perfused, myocardial function recovered better in IHA rats than that in normoxic control rats. CONCLU-SION: MA adaptation increased the tolerance of rat hearts against subsequent ischemia-reperfusion injury, and increase in coronary circulation and angiogenesis might be the mechanisms of myocardium protected by IHA.目的:为了阐述间歇性高海拔低氧对于大鼠心脏冠脉毛细血管以及冠脉血流的影响.方法:利用离体大鼠心脏Langendorff灌流模型来检测缺血复灌期的冠脉流量变化,利用免疫过氧化酶染色测定法和计算机辅助形态计量分析法来测定心脏毛细血管密度.利用放免方法检测心肌中cGMP的水平.结果:缺血前,间歇性低氧适应(IHA)的大鼠的冠脉流量水平(IHA28 13.4mL/min±1.5mL/min,IHA4215.4mL/min±2.0mL/min,P<0.01)要比常氧下的大鼠(11.0±0.8)mL/min高,IHA大鼠在缺血复灌后冠脉流量的恢复也较好.作为适应的结果,IHA大鼠左心室心肌毛细血管密度约为常氧大鼠的1.5倍,但没有发现明显的心室肥大.缺血复灌前后这两组的心肌cGMP的水平都没有改变.然而与常氧大鼠组比较,IHA训练大鼠的cGMP水平明显增加.在离体心脏灌流中,IHA大鼠缺血复灌后心功能的恢复较常氧组好.结论:IHA增加了大鼠心脏对缺血复灌损伤的耐受,IHA诱导的冠脉循环增加以及血管生长可能是IHA心肌保护效应的机制.
关 键 词:ALTITUDE ANOXIA ISCHEMIA reperfusion injury coronary circulation CAPILLARIES ANGIOGENESIS
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