JNK信号通路对缺氧诱导心房钠尿肽分泌的影响

Effects of JNK signaling pathway on hypoxia-induced ANP secretion

[目的]探讨JNK信号通路对缺氧诱导心房钠尿肽(ANP)分泌的影响及其机制.[方法]采用由氮气制作的家兔缺氧离体心房灌流模型;采用放射免疫法测定ANP及内皮素-1(ET-1)值.[结果]在家兔离体心房灌流模型中,急性缺氧明显促进心房ANP及ET-1的分泌;MAPK信号转导通路的JNK途径抑制剂SP600125明显抑制缺氧引起的ANP及ET-1的分泌;预处理SP600125或同时预处理2种ET-1受体阻断剂(BQ123+BQ788)均明显抑制缺氧诱导心房ANP的分泌,而SP600125对缺氧诱导ANP分泌的抑制作用明显强于BQ123+BQ788的抑制效应.[结论]急性缺氧明显增加离体心房ANP的分泌,JNK信号通路部分通过ET-1调节缺氧诱导ANP分泌的过程.

OBJECTIVE To study the effects of JNK on hypoxia-induced atrial natriuretic peptide（ANP） secretion and its mechanism. METHODS The isolated perfused beating rabbit atrial hypoxic model was established by nitrogen, and the ANP and endothelinl（ET-1） levels were measured by radioimmunoassay. RESULTS Acute hypoxia significantly increased the secretion of atrial ANP and ET 1. Pretreated with SP600125, an inhibitor of JNK of MAPK signal transduction pathway, significantly inhibited the effect of hypoxia-induced atrial ANP and ET 1 secretion, and pretreated with BQ123 and BQ788, inhibitors of type A and type B of endothelin receptors respectively, the hypoxia-induced atrial ANP secretion was markedly attenuated. However, the inhibitory effect of SP600125 on hypoxia-induced ANP secretion was stronger than that of BQ123 ＋ BQ788. CONCLUSION Acute hypoxia significantly increases the ANP secretion in isolated beating rabbit atria, and JNK signaling pathway is involved in the regulation of hypoxia-induced ANP secretion via ET-1.