Alveolar hypoxia increases gene expression of extracellular matrix proteins and platelet-derived growth factor-B in lung parenchyma
Alveolar hypoxia increases gene expression of extracellular matrix proteins and platelet-derived growth factor-B in lung parenchyma
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DOI：
10.1164/ajrccm.158.6.9804076
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发表时间：
1998-12-01
影响因子：
24.7
通讯作者：
West, JB
中科院分区：
文献类型：
--
作者：
Berg, JT;Breen, EC;West, JB
肺毛细血管壁极薄，当毛细血管压力升高时，壁应力大大增加。肺泡缺氧会导致肺血管收缩和高血压，如果这种情况不均衡，一些毛细血管可能会暴露在高跨壁压力下，并发展为应激衰竭。有证据表明，壁应力增加会导致毛细血管重塑。本研究将Madison品系SD大鼠暴露于常压低氧(10%氧气)6h或3d(短期组)和3d或10d(长期组)。然后收集周围肺组织，测定细胞外基质(ECM)蛋白和生长因子的信使RNA(MRNA)水平。同时测定胶原含量(羟脯氨酸)。α2(IV)前胶原基因表达水平在缺氧6h后增加6倍，缺氧3d后增加7倍，10d后下降。血小板衍生生长因子-B(PDGF-B)的mRNA水平在缺氧6h后增加一倍，3d后恢复至对照组水平，α1(I)、α1(III)前胶原和纤维连接蛋白的mRNA水平在缺氧3d后升高(分别增加7~12倍、1.6~8倍和12倍)，10d后下降至对照组水平。这些结果表明，肺泡低氧可引起肺实质血管重塑，并与壁应力增加所致的毛细血管重塑一致。
The walls of pulmonary capillaries are extremely thin, and wall stress increases greatly when capillary pressure rises. Alveolar hypoxia causes pulmonary vasoconstriction and hypertension, and if this is uneven, some capillaries may be exposed to high transmural pressure and develop stress failure. There is evidence that increased wall stress causes capillary remodeling. In this study we exposed Madison strain Sprague-Dawley rats to normobaric hypoxia (10% oxygen) for 6 h or 3 d (short-term group), and for 3 d or 10 d (long-term group). Peripheral lung tissue was then collected and messenger RNA (mRNA) levels were determined for extracellular matrix (ECM) proteins and growth factors. Collagen content (hydroxyproline) was also measured. Levels of mRNA for alpha 2(IV) procollagen increased sixfold after 6 h of hypoxia and sevenfold after 3 d of hypoxia, and then decreased after 10 d exposure. Levels of mRNA for platelet-derived growth factor-B (PDGF-B) doubled after 6 h of hypoxia but returned to control values after 3 d. mRNA levels for alpha 1(I) and alpha 1(III) procollagens and fibronectin were increased after 3 d of hypoxia (by seven- to 12-fold, 1.6- to eightfold, and 12-fold, respectively), then decreased toward control values after 10 d. In contrast, neither levels of mRNA for vascular endothelial growth factor (VEGF) nor collagen content changed. These results suggest that alveolar hypoxia causes vascular remodeling in lung parenchyma, and are consistent with capillary wall remodeling in response to increased wall stress.