间歇性高海拔低氧适应对大鼠缺血耐受的心肌毛细血管生成以及冠脉血流的影响

摘要

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 13.4 mL/min±1.5 mL/min,IHA4215.4 mL/min±2.0 mL/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:IH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.%AIM: To determine the effects of simulated intermittenthigh altitude hypoxia adaptation (IHA) on coronarycapillary and coronary flow (CF) in rat hearts.METHODS: Model of Langendorf-perfused isolated rathearts were used to measure CF during ischemia-reperfusion, and immunoperoxidase staining assay andcomputer-aid morphometry analysis were conducted todetermine the myocardial capillary densities. CyclicGMP (cGMP) level in myocardium was measured byradio-immunoassay. RESULTS: Pre-ischemia level ofCF in IHA rats was higher (IHA28 13.4 mL/min ± 1.5mL/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 wasbetter in IHA rats. As an adaptive result, the myocardialcapillary densities of the left ventricular myocardium inIHA rats were 1.5 times of those in normoxic controlrats, but there was no apparent ventricular hypertrophy inIHA rats. Myocardial cGMP content ( 1.8 ± 0.7) nmol/g in IHA rars were increased significantly compared withcontrol rats ( 1.1 ± 0.4) nmol/g, but cGMP level wasnot altered before and after ischemia-reperfusion in eithergroup. It was also revealed that in isolated rat heartsperfused, myocardial function recovered better in IHArats than that in normoxic control rars. CONCLUSION: IHA adaptation increased the tolerance of rathearts against subsequent ischemia-reperfusion injury, andincrease in coronary circulation and angiogenesis might bethe mechanisms of myocardium protected by IHA.