缺氧预处理对于老年大鼠心肌顿抑的影响

The effects of hypoxic preconditioning on myocardial stunning in aged rats

目的 探讨缺氧预处理对于老年大鼠心肌顿抑的影响及其保护机制。方法 老年和成年SD大鼠分别随机分为单纯心肌顿抑组、缺氧预处理 +心肌顿抑组、SB2 0 35 80 +缺氧预处理 +心肌顿抑组和假手术组 4组 ,采用在体心脏心肌顿抑模型 ,观察缺氧预处理对于心肌舒缩功能、乳酸脱氢酶、肌酸激酶漏出和亚硝酸盐含量的影响 ,以及p38丝裂素活化蛋白激酶 (p38MAPK)选择性抑制剂SB2 0 35 80对于缺氧预处理作用的影响。结果 缺氧预处理明显减轻老年大鼠心肌收缩功能抑制的程度 ,与单纯心肌顿抑组比较 ,收缩期左心室内压力变化最大速率 (+dp dtmax)和零负荷时左室心肌最大收缩速率 (Vmax)分别高 35 %和 4 9% (P <0 .0 5 )。缺氧预处理减轻再灌注结束时心肌顿抑大鼠血清亚硝酸盐的下降程度 ,与老年心肌顿抑组大鼠比较 ,其含量高 5 4 % (P <0 .0 1) ,SB2 0 35 80 2消除缺氧预处理上调血清亚硝酸盐含量和老年大鼠心肌收缩功能的保护作用。结论 缺氧预处理可以减轻老年大鼠心肌顿抑所致收缩功能抑制 ,其保护机制涉及p38MAPK介导的一氧化氮的上调。

Objective To investigate the effects of hypoxic preconditioning on myocardial stunning and its protective mechanism.Methods Aged and adult SD rats were randomly assigned to the following groups: myocardial stunning(MS), hypoxic preconditioning (HPC+MS), p38 MAPK inhibitor+HPC+MS, and sham operation group, respectively. In a model of myocardial stunning in vivo, the cardiac function, activities of serum lactate dehydrogenase (LDH), creatine kinase (CK), and nitrite/nitrate content were measured.The effects of SB2035802,a slective inhibitor of p38 mitogen activated protein kinase (p38 MAPK),on HPC were observed.Results Compared with myocardial stunned rats, hypoxic preconditioning improved cardiac contractility of aged rats subjected to myocardial stunning by increasing +dp/dt and Vmax by 35% and 49% (P<0.05), respectively, but did not improve -dp/dt and LVDP (P>0.05). Hypoxic preconditioning also increased serum nitrite/nitrate content by 54% (P<0.05) as compared with myocardial stunning group.SB2035802 completely abolished the protective effects of HPC on myocardial stunning and the upregulation of serum nitrite/nitrate.Conclusions Hypoxic preconditioning can attenuate the inhibition of cardiac contractility resulting from myocardial stunning. The upregulation of NO induced by activation of p38 MAPK might be involved in the protective mechanism.