缺氧对肺动脉内皮细胞PDGF─A、─B链及其受体α、β亚基基因表达的影响

Effects of hypoxia on expression of A and B chains of platelet derived growth factor and their α and β subunit receptors in cultured pulmonary arterial endothelial cells

为了研究缺氧性肺动脉高压形成的机理，采用核酸分子杂交技术观察缺氧对肺动脉内皮细胞（ＰＡＥＣ）血小板源性生长因子（ＰＤＧＦ）－Ａ链、－Ｂ链及其受体α、β亚基基因表达的影响。结果表明低氧和无氧（２．５％Ｏ２和０％Ｏ２）１．５、３ｈＰＡＥＣ的ＰＤＧＦ－Ａ链ｍＲＮＡ表达显著增加（Ｐ＜０．０１，ｖｓ常氧组），而６～４８ｈＰＤＧＦ－Ａ链ｍＲＮＡ表达水平无明显改变。低氧和无氧１．５～４８ｈ均能显著地增加ＰＡＥＣ的ＰＤＧＦ－Ｂ链ｍＲ－ＮＡ表达（Ｐ＜０．０５）。常氧条件下ＰＡＥＣ均能低水平地表达ＰＤＧＦ－α亚基受体和β亚基受体，低氧和无氧则上调此两受体ｍＲＮＡ表达水平（Ｐ＜０．０５）。由此说明缺氧不仅能使ＰＡＥＣ“旁分泌”ＰＤＧＦ参与肺动脉平滑肌细胞增殖调节，也使ＰＡＥＣ通过“自分泌”ＰＤＧＤ及上调其膜上的ＰＤＧＦ受体基因表达，参与缺氧肺动脉内皮细胞自身功能调节，从而在缺氧性肺动脉高压肺血管收缩反应增强及肺血管结构改建中发挥重要作用。

In order to explore the mechanisms of hypoxic pulmonary artery hypertension (HPAH), the effects of hypoxia on the expression of the A and B chains of platelet derived growth factor (PDGF) and their α and β subunit receptors in cultured pulmonary arterial endothelial cells (PAECs) were observed with dot blot hybridization. It was found that mRNA expression of A chain of PDGF was significantly increased when PAECs were incubated under hypoxic (2.5% O 2) and anoxic (0% O 2) condition for 1.5 to 3 h ( P <0.01), but it remained unchanged when PAECs were incubated likewise for 6 to 48 h. The mRNA expression of the B chain of PDGF was significantly increased from 1.5 to 48 h after the incubation ( P <0.05). PAECs could express α and β subunit receptors of PDGF in low level under normoxia but hypoxia and anoxia significantly upregulated mRNA expression of the two receptors ( P <0.05). Our findings suggest that hypoxia play an important role not only in modulating the proliferation of pulmonary arterial smooth muscle cells through stimulating the paracrine of PDGF by PAECs but also in regulating the functions of PAECs through stimulating the autocrine of PDGF by PAECs and upregulating gene expression of PDGF receptors on the membrane of PAECs. This may contribute to the increase of contractility and structural changes of pulmonary arteries in HPAH.