缺氧大鼠出、入肺血、肺组织及心室肌降钙素基因相关肽和内皮素-1含量的变化

目的和方法:采用放免法观察常压间断缺氧大鼠出、入肺血和肺及心室肌组织匀浆中降钙素基因相关肽(CGRP)和内皮素-1(ET-1)的含量变化,并分析其与缺氧性肺动脉高压(HPH)和右心肥大间的相关关系。结果:正常大鼠入肺血CGRP含量显著高于出肺血,而ET-1含量和ET-1/CGRP比值则显著低于出肺血(P<0.01);随缺氧时间的延长,缺氧大鼠出肺血CGRP含量显著升高(P<0.05),与其肺动脉平均压(mPAP)呈正相关,而ET-1/CGRP比值则明显降低(P<0.05),与其mPAP呈负相关(r=-0.896,P<0.05);与对照组比较,缺氧大鼠入肺血及肺组织匀浆中CGRP和ET-1的含量及ET-1/CGRP比值均呈现先升高后降低趋势,至缺氧21d时入肺血的3项指标均接近正常水平;缺氧21d大鼠出肺血CGRP含量显著高于其入肺血(P<0.05)。结论:结果提示肺内CGRP和ET水平的失调在慢性HPH和右心肥大发生机制中起重要的作用。

Levels of CGRP and ET-1 in plasma of pulmonary artery and thoracic aorta and in the extractives of lung and ventricular tissues of the chronic hypoxic rats

AIM AND METHODS: To explore the effects calcitonin gene-related peptide (CGRP) and endothelin-1(ET-1) on the mechanisms of hypoxic pulmonary hypertension (HPH),the contents of CGRP and ET-1 in plasma of pulmonary artery and thoracic aorta and in extractives of lung and ventricular tissues of the chronic hypoxic rats were determined by radioimmunoassay. The changes of their hemodynamic indices and right heart hypertrophy index were monitored simultaneously. RESULTS: The level of pulmonary artery plasma CGRP was significantly higher than that of thoracic aorta plasma,but just the reverse was ET-1 or the ratio of ET-1 and CGRP in control rats( P <0.01). Compared with controls,the level of pulmonary artery plasma CGRP was gradually reduced in all hypoxic rats,but ET-1 was enhanced after 7 and 14 days of hypoxia and was decreased after 21 days of hypoxia. With prolonging time exposed to hypoxia,the level of thoracic aorta plasma CGRP was markedly increased in hypoxic animals compared with controls ( P <0.05),the positive correlation significantly with increased pulmonary arterial pressure( r = -0.896 ,P =0.05),but the lower level of thoracic aorta plasma ET-1 showed or negative correlation with pulmonary arterial pressure. CONCLUSIONS: These data suggest that the unbalance of effects of CGRP and ET may plays an important role in regulating the resistance of pulmonary circulation and has close relation with the formation of HPH.