间歇性低氧预处理对慢性缺血心脏保护作用的实验研究

The protective effect of intermittent hypoxic preconditioning on ischemic heart in rabbits

目的:采用冠状动脉左前降支部分结扎的方法复制慢性心肌缺血的动物模型,观察间歇性低压低氧预处理对缺血心脏泵功能的保护作用.方法:成年雄性新西兰家兔22只,体质量2.0～2.5 kg,随机分为2大组:对照组(C组,n=11)和间歇性低压低氧预处理组(H组,n=11).两组动物均先进行冠状动脉左前降支部分结扎,7 d手术恢复期后,H组动物开始间歇性低压低氧预处理(5000 m,6 h/d,连续7 d者为H1组,42 d者为H2组),C组动物分为C1、C2组常规饲养(实验时间分别与H1、H2组相同).按计划完成实验后,测定各组动物心率(HR)、左室收缩期内压最大变化速率(LVdp/dtmax)及左室舒张期内压最大变化速率(-LVdp/dtmax),然后给予急性缺氧,重复测定上述指标,并与急性缺氧前所测相应各值比较,观察各组动物对急性缺氧的耐受性.同时观察各组动物的心肌细胞的超微结构及心肌VEGF mRNA的表达.结果:急性缺氧时,H2组HR的下降程度显著小于其它3组(P＜0.01);LVdp/dtmax的下降程度显著小于C2组(8.5% vs 30.5%,P＜0.01).恢复常氧后,H2组的LVdp/dtmax恢复程度显著优于C2组(下降率为0.9% vs 18.6%,P＜0.01);-LVdp/dtmax恢复程度亦优于C2组及其它2组(P＜0.05).H2组动物心肌线粒体数量增加.经低氧预处理后心肌组织的血管内皮生长因子(VEGF)mRNA表达明显增高.结论:长期间歇性低压低氧预处理能增强缺血心脏对急性缺氧的耐受性,对慢性局灶性缺血心脏有保护作用.

AIM： To determine the protective effect of intermittent hypoxia （IH） precondition on ischemic heart by using a rabbit model of chronic myocardial ischemia with left anterior descending （LAD） banding. METHODS：Male, adult New Zealand white rabbits were assigned into two groups randomly. ① Control group （ C group）, ② IH precondition group （ H group）. A LAD band was placed in the animals＇heart first. After 7 days recovered period, the rabbits in H group were exposed to altitude of 5000 m, for 6 h/day continuously. According to IH precondition duration, the animals were subdivided into HI group for 7 days and H2 group for 42 days. C group was subdivided into C1 group and C2 group to compare with HI and H2 group. After these experiments, the heart rate, LVdp/dt were examined and observed changes of heart rate, LVdp/dtmax during acute hypoxia in the animals of all groups. The microstructure of cardiomyocyte and expression of VEGF mRNA were studied. RESULTS： During acute hypoxia, the decrease of heart rate was much smaller in H2 group than other groups （ P 〈0.01 ）. The decrease of LVdp/dtmaX in H2 group was much smaller than C2 group （8.5% vs 30.5% , P 〈 0.01 ）. After acute hypoxia, the recovering of ± LVdp/dtmax in H2 group were also much better. The expressions of VEGF mRNA were increased in H group significantly. CONCLUSION： Long term IH precondition improves the ability of chronic inchemic myocardium to resist acute hypoxia stress. The intermittent hypoxia precondition has protective effect on ischemic heart.