血管紧张素-（1-7）对快速心房起搏犬心房重构及p38MAPK蛋白表达的影响

目的:观察快速心房起搏后犬心房重构与p38MAPK蛋白激活的关系，以及血管紧张素（Ang）-(1-7)的干预作用。方法:普通杂种犬15只随机分为3组，假手术组（Sham，S组）、心房起搏组（Pacing，P组）和心房起搏+Ang-(1-7)组（A组），每组5只，所有犬均安置心房起搏器，除假手术组外，其余两组均给予500次/min持续右心房起搏，A组以6 μg/（kg·h）连续给予Ang-（1-7），起搏2周后分别测定各组犬的心脏结构变化、心房有效不应期、房颤诱发率及持续时间，HE染色及Masson染色观察心房肌细胞结构变化，Western blot技术测定左心房组织p38MAPK、磷酸化p38MAPK的蛋白表达情况。结果:与假手术组比较，心房起搏组左室射血分数降低，心房有效不应期缩短，房颤诱发率及持续时间升高，心肌细胞排列紊乱，细胞间纤维组织增多，磷酸化p38MAPK水平明显升高（P＜0.05)，Ang-(1-7)组较心房起搏组左室射血分数、心房有效不应期、房颤诱发率及持续时间均明显改善，磷酸化p38MAPK蛋白降低（P＜0.05），但p38MAPK在3组间的差异未达到统计学意义。结论:快速心房起搏导致的心房重构与p38MAPK磷酸化激活有关，Ang-（1-7）可通过降低p38MAPK激活而保护心房重构。

Effect of angiotensin-(1-7) on atrial remodeling and p38MAPK expression in a canine model of rapid atrial pacing

Objective: To observe the relationship between atrial remodeling and p38MAPK activation in rapid atrial pacing model, and the intervention of angiotensin-(1-7). Methods: Fifteen mongrel dogs of either sex were randomly assigned to the sham-operated group（S, n=5）, pacing group（P, n =5）and paced+ Ang-(1-7)group（A, n=5）. All dogs were placed a programmable atrial pacemakers. Except for the S group, and the other two groups were given 500 beats per minute for continuously right atrial pacing. Dogs in group A were additionally given Ang-(1-7) 6 μg/（kg·h）. After 2 weeks of pacing, the changes of cardiac structure, atrial effective refractory period, AF inducibility and duration were measured. HE staining and Masson staining were used to observe the changes of atrial structure. Western blot was applied to access the expression of p38MAPK，phosphorylated p38MAPK in the left atrial tissue. Results: In the P group, left ventricular ejection fraction decreased, AERP shortened, AF inducibility and duration increased, myocardial cells were disordered, and intercellular fibrous tissue increased. The phosphorylated p38MAPK levels in the P group were significantly higher than in the S group(P < 0.05). While the left ventricular ejection fraction, AERP, AF inducibility and duration of the A group were significantly improved and phosphorylated p38MAPK protein was decreased(P <0.05). But the difference of p38MAPK among the three groups was not statistically significant. Conclusion: Atrial remodeling induced by rapid atrial pacing may be associated with phosphorylation of p38MAPK, and Ang-(1-7) may protect atrial structure by reducing p38MAPK activation.