低氧大鼠肾上腺髓质素对其前体N端20肽和肺血管结构重构的影响

Effect of adrenomedullin on proadrenomedullin N-terminal 20-peptide and hypoxic pulmonary vascular structural remodeling in rats

目的探讨肾上腺髓质素(ADM)对低氧性肺动脉高压大鼠肺血管结构重构和肾上腺髓质素前体N端20肽(PAMP)的影响。方法24只雄性Wistar大鼠随机分为对照组、低氧组、低氧+ADM组,每组各8只。低氧+ADM组大鼠,通过微量渗透泵皮下持续给予ADM(300 ng/h)。用放免法测定血浆中PAMP含量,用免疫组化法检测肺组织中PAMP表达。结果低氧2周后,大鼠肺动脉平均压、右心室与左心室加室间隔的比值、肺动脉相对中膜厚度和面积较对照组均明显增高(P<0.01),超微结构也发生了明显改变。并且低氧组大鼠血浆PAMP含量明显升高,肺动脉PAMP表达明显增强。而ADM可显著缓解上述变化。结论ADM分子内调控参与了ADM对于低氧性肺动脉高压的干预机制。

Objective To investigate the effect of adrenomedullin （ADM） on hypoxic pulmonary vascular structural remodeling and proadrenomedullin N-terminal 20-peptide （PAMP） in rats with hypoxic pulmonary hypertension. Methods Twenty-four male Wistar rats were randomly divided into control group （ n = 8）, hypoxia group （ n = 8） and hypoxia with ADM group （ n = 8）. ADM was subcutaneously administered into rats of hypoxia with ADM group by mini-osmotic pump （300 ng/h）. The concentration of plasma PAMP was measured by radioimmunoassay, and the expression of PAMP in pulmonary artery was detected by immunohistochemical assay. Results Mean pulmonary arterial pressure, the ratio of right ventricular mass to left ventricular plus septal mass, and relative medial thickness and relative medial area of pulmonary arteries significantly increased in hypoxic rats as compared with that of controls （P 〈 0. 01, respectively）. Ultrastructural changes Meanwhile, plasma PAMP concentration and the were also found in pulmonary arteries of hypoxic rats. expression of PAMP by pulmonary arteries in hypoxic rats were markedly increased compared with controls. However, ADM obviously ameliorated above changes. Conclusion Intramolecular regulation of ADM may play an important role in the regulation of hypoxic pulmonary hypertension by ADM.