高肺血流性肺动脉高压大鼠肾上腺髓质素前体N端20肽的变化

Alterations of proadrenomedullin N-terminal 20-peptide in rats with pulmonary hypertension induced by high pulmonary blood flow

摘要:

目的：高肺血流性肺动脉高压的形成机制至今尚未完全阐明。该实验通过研究高肺血流性肺动脉高压大鼠肺组织肾上腺髓质素前体N端20肽( PAMP ) 表达以及血浆PAMP含量的变化，探讨PAMP在高肺血流性肺动脉高压形成中的作用。方法：16只雄性SD大鼠随机分为对照组和分流组，每组各8只。对分流组大鼠行腹主动脉-下腔静脉分流术。11周后，以右心导管法测定肺动脉收缩压（sPAP）、肺动脉舒张压（dPAP）和肺动脉平均压（mPAP），观察肺动脉超微结构的变化。并且以放射免疫法测定血浆中PAMP含量，以免疫组织化学法检测肺组织中PAMP表达。结果：分流组大鼠sPAP、dPAP和mPAP均明显高于对照组（均P<0.01）。电镜下，肺腺泡内动脉内皮细胞增生、肿胀，内弹力层不规则，平滑肌细胞肥厚、向合成表型转化。并且分流组大鼠血浆PAMP含量明显高于对照组（P<0.01），肺动脉内皮细胞和平滑肌细胞PAMP表达明显增强。结论：肺动脉和血浆PAMP表达的上调可能参与了高肺血流性肺动脉高压的形成。［中国当代儿科杂志，2007，9（6）：574-576］

Abstract:

OBJECTIVE: The mechanism of high pulmonary blood flow-induced pulmonary hypertension remains unclear. The aim of this study was to explore the effect of proadrenomedullin N-terminal 20peptide (PAMP) on pulmonary hypertension, through examining the alterations of pulmonary PAMP expression and plasma PAMP concentration in rats with pulmonary hypertension induced by high pulmonary blood flow. METHODS: Sixteen male Sprague-Dawley rats were randomly divided into control (n=8) and shunt groups (n=8). Aortocaval shunting was produced in the shunt group. After 11 weeks of shunting, systolic pulmonary artery pressure (sPAP), diastolic pulmonary artery pressure (dPAP) and mean pulmonary artery pressure (mPAP) were evaluated by using a right cardiac catheterization procedure. The ultrastructural changes in intra-acinar pulmonary arteries were observed. The concentration of plasma PAMP was measured by radioimmunoassay. The expression of PAMP in pulmonary arteries was detected by immunohistochemical assay.RESULTS: sPAP, dPAP and mPAP were significantly increased in shunt rats compared with controls (P<0.01). Ultrastructural changes, such as hyperplasia and swelling of endothelial cells, irregularity of internal elastic laminar, and hypertrophy and increased number of synthetic phenotype of smooth muscle cells, were found in intra-acinar pulmonary muscularized arteries in the shunt group. Plasma PAMP concentration (616±195 pg /mL vs 427±90 pg /mL) and PAMP expression in endothelial cells (0.62±0.09 vs 0.38±0.12) and in smooth muscle cells (0.24±0.07 vs 0.14±0.05) of pulmonary arteries increased significantly in the shut group compared with controls. CONCLUSIONS: The up-regulation of pulmonary and plasm PAMP expression might be involved in the development of high pulmonary blood flow-induced pulmonary hypertension.［Chin J Contemp Pediatr, 2007, 9 (6):574-576］