腺苷通过NHE-1/CaN途径拮抗大鼠低氧性右心室心肌肥厚  

Adenosine alleviates hypoxia-induced rat right ventricular hypertrophy through the NHE-1/CaN signal pathway

作　　者：林明静[1] 黄秀兰[1] 谭建新[1] 王波[1] 

机构地区：[1]广东医学院附属医院儿童医学中心,广东湛江524023

出　　处：《南方医科大学学报》2012年第5期734-737,共4页Journal of Southern Medical University

基　　金：广东省科学自然基金(8152402301000018)

摘　　要：目的观察腺苷及其激动剂拮抗右心室肥厚的作用,并探讨其作用机制。方法 56只Sprague-Dawley大鼠随机分成常氧对照组、低氧对照组、低氧处理组（低氧＋腺苷组、低氧＋腺苷A1受体激动剂（CPA）、低氧＋腺苷A2受体激动剂（NECA）、低氧＋CPA＋A1受体阻滞剂（DPCPX）、低氧＋NECA＋A2b受体抑制剂MRS1754组）。大鼠置于低氧仓（氧浓度为9.5%~10.5%）连续低氧21 d。各处理组于低氧第7天使用植入式胶囊渗透压泵给药,持续时间为14 d,实验终点时,测定大鼠右心室肥厚程度,采用PCR法检测右心室心肌组织中NHE-1 mRNA、CnAβmRNA的相对含量。结果 1、慢性低氧对照组大鼠RV/（LV＋S）为0.369±0.033、RV/BW比值为0.75±0.095,均明显高于常氧组（0.271±0.010,0.59±0.039）（均P〈0.001）及低氧腺苷处理组（0.281±0.022,0.650±0.077）（P〈0.001,P=0.025）低氧＋CPA组（0.313±0.021,0.66±0.067）（均P〈0.001）、低氧＋NECA组（0.333±0.019,0.68±0.074）（均P〈0.001）;2、右心室心肌NHE-1 mRNA、CnAβmRNA表达在低氧组均高于常氧组（均P〈0.001）及腺苷处理组低氧＋CPA、低氧＋NECA组（均P〈0.001）。结论腺苷及其受体激动剂可通过NHE-1/CaN信号通路拮抗低氧性右心室心肌肥厚。Objective To investigate the effect of adenosine and its agonist on hypoxia-induced right ventricular hypertrophy（RVH） and explore the underlying mechanism.Methods Fifty-six rats were randomly divided into normoxia group,hypoxia group,and treated hypoxia groups（with different treatments with adenosine,A1 receptor agonist CPA,A2 receptor agonist NECA,CPA plus A1 receptor inhibitor DPCPX,or NECA plus A2B receptor inhibitor MRS1754）.The rats except for those in normoxia group were exposed to normobaric chronic hypoxia（9.5%-10.5% oxygen） for 21 days,and the corresponding treatments were administered since the 7th day of hypoxia till day 21 via implantable capsule with a pressure pump.After the treatments,the right ventricles were then removed and weighed for evaluation of hypertrophy,and the expressions of NHE-1 and CnAβ mRNA in the myocardial tissue were detected using RT-PCR.Results After a 21-day hypoxia,the rats showed significantly increased RV/（LV＋S） ratio（0.369±0.033） and RV/BW ratio（0.75±0.095） compared to those in normoxia group（0.271±0.010 and 0.59±0.039,respectively;P0.001）,adenosine treatment group（0.281±0.022 and 0.65±0.077,respectively;P0.001,P=0.025）,hypoxia with CPA group（0.313±0.021and 0.66±0.067,respectively P0.001）,and hypoxia with NECA group（0.333±0.019,and 0.68±0.074,respectively P0.001）.The NHE-1 and CnAβ mRNA levels in hypoxia group were significantly higher than those in normoxia group,adenosine treatment group,hypoxia with CPA group,and hypoxia with NECA group（P0.001）.Conclusion Adenosine and its agonist can inhibit hypoxia-induced RVH in rats through the NHE-1/CaN signal pathway.

关 键 词：腺苷 低氧 心肌肥厚 NHE-1 

分 类 号：R363[医药卫生—病理学]