慢性快速心房起搏心房颤动犬内皮型一氧化氮合酶mRNA表达变化的研究

Changes of Endothelial Nitric Oxide Synthase mRNA Expression in the Canine Atrial Fibrillation Model With Chronic Rapid Atrial Pacing.

为研究慢性快速心房起搏心房颤动(简称房颤)犬模型中心内膜内皮型一氧化氮合酶(eNOS)mRNA表达的变化,探讨其与心房结构重构、血栓形成的关系。13只健康犬随机分为假手术组和起搏组,应用埋藏式高频率心脏起搏器快速起搏心房(400次 /分) 6周,取左、右心房,左、右心耳及主动脉内膜。通过逆转录 聚合酶链反应 (RT PCR),以β actin为内参照,测定犬心内膜eNOSmRNA表达的变化,同时检测血浆NO代谢产物硝酸盐 (NOx)的含量。结果:正常犬心脏eNOSmRNA表达存在差异,左房、左心耳明显高于右房、右心耳;起搏 6周后左房、左心耳eNOSmRNA表达起搏组明显低于假手术组,而右房、右心耳、主动脉无明显差别,血浆NOx起搏组亦明显低于假手术组。结论:正常犬心脏eNOS基因表达是不平衡的,左房明显高于右房。房颤犬eNOSmRNA表达降低可能是心房结构重构,血栓形成的重要因素之一。

The goal of the present study is to investigate the changes of endothelial nitric oxide synthase (eNOS) mRNA expression in the canine atrial fibrillation(AF) model with chronic rapid atrial pacing and to explore the mechanisms of atrial structural remodeling and thrombosis in canines with AF. In 7 dogs, AF was produced with rapid atrial pacing at 400 bpm for 6 weeks, whereas controls(n=6) had no atrial pacing. 30 mg tissue each was obtained from the left and right atrium, left and right atrial appendage and aortas of 13 dogs. The changes of eNOS mRNA were measured by reverse transcription-polymerase chain reaction(RT-PCR) and they were normalized to the β-actin. At the same time the plasma levels of NOx were analyzed.Results: The normal canine eNOS mRNA was significantly higher in left atrium(LA) and left atrial appendage(LAA) than in right atrium(RA) and right atrial appendage(RAA) (4.26±0.96 vs 2.45±0.57; 4.88±1.02 vs 2.36±0.56 ,all P<0.05). eNOS mRNA of the LA and LAA were significantly decreased in dogs after they were produced with rapid atrial pacing at 400 bpm for 6 weeks(LA: 1.15±0.29 vs 4.26±0.96, P<0.05;LAA: 1.56±0.38 vs 4.88±1.02, P<0.01), whereas it did not change significantly in the RA, RAA and the aorta. The plasma levels of NOx were also decreased in atrial pacing group 31.8±7.4μmol/l vs 52.3±12.9μmol/l, P<0.05.Conclusion:The expression of eNOS mRNA in normal canine endocardium is unbalanced. The decreased expression of eNOS mRNA in left atrium may play a role in atrial remodeling and thrombosis in canines with AF.