慢性低氧性肺动脉高压大鼠肾上腺髓质素前体N端20肽的变化

目的：探讨慢性低氧性肺动脉高压和肺血管结构重建时肾上腺髓质素前体N端20肽（PAMP）的变化。方法:将18只雄性Wistar大鼠随机分为对照组和低氧组，每组各9只。常压低氧2周后，以右心导管法测定肺动脉平均压（mPAP），检测右心室与左心室加室间隔比值 ［RV/(LV+S)］，观测肺血管显微和超微结构的变化。并且以放免法测定血浆中PAMP含量，以免疫组化法检测肺组织中PAMP表达，以原位杂交检测肺组织中肾上腺髓质素（ADM） mRNA的表达。结果: 低氧组大鼠mPAP及RV/（LV+S）均明显高于对照组（均P<0.01）。光镜下，肺小血管肌化程度明显增强，肺中、小型肌型动脉相对中膜厚度明显增加。电镜下，肺腺泡内动脉内皮细胞增生、肿胀，内弹力层粗细不均，平滑肌细胞肥厚、向合成表型转化。并且低氧组大鼠血浆PAMP含量明显高于对照组（P<0.01），肺动脉PAMP表达和ADM mRNA表达均明显增强。结论：低氧后肺动脉PAMP表达和血浆PAMP含量的上调可能参与了慢性低氧性肺动脉高压和肺血管结构重建的形成。

Alteration of proadrenomedullin N-terminal 20-peptide in rats with chronic hypoxic pulmonary hypertension

AIM:To examine the alteration of proadrenomedullin N-terminal 20-peptide (PAMP) in rats with chronic hypoxic pulmonary hypertension and pulmonary vascular structural remodeling. METHODS:Eighteen male Wistar rats were randomly divided into control group (n=9) and hypoxic group (n=9). After two-week hypoxic challenge, mean pulmonary arterial pressure (mPAP) of each rat was evaluated by using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass ［RV/(LV+S)］ was detected. Pulmonary vascular microstructure was measured and the ultrastructural changes in intra-acinar pulmonary arteries were observed. Meanwhile, the concentration of plasma PAMP was measured by radioimmunoassay. The expression of PAMP by pulmonary arteries was detected by immunohistochemical assay, and the expression of adrenomedullin (ADM) mRNA in pulmonary arteries was detected by in situ hybridization.RESULTS:mPAP and RV/(LV+S) were significantly increased in rats exposed to two-week hypoxia (P<0.01, respectively). Muscularization of small pulmonary vessels and relative medial thickness of pulmonary arteries were obviously increased in hypoxic rats compared with controls. Ultrastructural changes, such as hyperplasia and swelling of endothelial cells, irregularity of internal elastic laminar, hypertrophy and the increased number of synthetic phenotype of smooth muscle cells, were found in intra-acinar pulmonary muscularized arteries of hypoxic rats. Meanwhile, plasma PAMP concentration was increased. The PAMP protein and ADM mRNA expressions in pulmonary arteries were significantly augmented in rats of hypoxic group as compared with control group.CONCLUSION:The up-regulation of PAMP due to hypoxia is probably involved in the development of chronic hypoxic pulmonary hypertension and pulmonary vascular structural remodeling.