缺氧性肺动脉高压大鼠肺组织中肾上腺髓质素的合成释放及其意义

目的 探讨缺氧性肺动脉高压（HPH）肺组织中肾上腺髓质素（AM）的合成分泌及其在HPH病理生理过程中的作用。方法 模拟5km高原连接缺氧，复制大鼠HPH动物模型。应用光镜、免疫组化、放射免疫测定等方法，观察测定缺氧后10d、20d、30d和对照组大鼠肺组织中AM蛋白表达及血浆、支气管肺泡灌洗液（BALF）AM含量的动态变化。结果 各组大鼠肺血管内皮细胞（EC）、血管及支气管平滑肌细胞（SMC）、支气管粘膜上皮、肺巨噬细胞（MΦ）、Ⅱ型肺泡上皮及支气管软骨细胞AM均呈阳性表达。缺氧各时相，尤以20d，上述各种细胞表达明显增强；其中EC、SMC、MΦ表达呈强阳性，各时相血浆AM含量显著高于对照组（P＜0.01）。BALF AM含量于缺氧10－20d显著高于对照组（P＜0.01），且20d明显高于10d;30d含量下降，趋于正常。结论 缺氧可促使肺组织中AM的合成和释放。AM作为一种局部激素及循环激素，对HPH病理过程中肺循环、肺通气、气道免疫及肺血管结构改建等方面发挥重要的调节作用。

Synthesis and release of pulmonary tissue adrenomedullin on hypoxic pulmonary hypertension in rats and its significance

OBJECTIVE: To investigate the synthesis and release of adrenomedullin (AM) of lung tissue in rats on hypoxic pulmonary hypertension (HPH) and study its mechanism and significance in the pathogenesis process of HPH. METHODS: 54 Wistar rats were divided into hypoxia 10 d (n = 12), 20 d (n = 12), 30 d (n = 12) groups and control group (n = 18). The rats of hypoxia groups were exposed to chronic hypobaric hypoxia environment at high 5 km to establish HPH models. The expression of pulmonary cell AM protein, the content of plasma AM and bronchial alveolar lavage fluid (BALF) AM were determined by optical microscopy, immunohistochemistry and radio-immunoassay. RESULTS: AM was widely distributed in lung tissue. There was positive of AM in intraplasma of vascular endothelial cells (EC), vascular and bronchial smooth muscular cells (SMC), bronchial epithelial cells, macrophages (M phi) and type II alveolar epithelial cells in every groups. After hypoxia, the expression of AM in above cells, especially EC, SMC and M phi, increased more than control group. Plasma AM contents of hypoxia groups were higher than control group(P < 0.01). 20 d after hypoxia, the AM content was twice as control group. At 10 d to 20 d after hypoxia, BALF AM content was increased more than control group (P < 0.01). But at 30 d the content was decreased near to normal. CONCLUSIONS: Hypoxia is effective in promoting AM synthesis and release in pulmonary tissue and suggestes that AM as a peptide plays an important regulating role on pulmonary circulation, exchange of air and pulmonary vascular structural remodeling in the pathophysiological process of HPH.