中文摘要：

目的：通过观察慢性阻塞性肺疾病（COPD）患者肺小动脉内低氧诱导因子α亚基（HIF-1α）及HIF脯氨酸羟化酶（PHD）、HIF抑制因子的表达，探讨其在肺血管重塑中的可能作用。方法：选因肺肿瘤行肺叶切除者，COPD组（12例），对照组（14例）。取2组患者的肺组织，原位杂交和免疫组化检测HIF-1α、PHD1、PHD2、PHD3、FIH的mRNA及蛋白表达水平。观察并计算肺小动脉管壁厚度（PAMT）7L肺小动脉管壁面积与血管总面积的比值（WA％）。结果：①COPD组PAMT（40μm±5μm）、WA％（50％±9％）均较对照组（分别为（31μm±4μm，39％±6％）高（均P〈0．01）；②COPD组肺小血管mF-1α mRNA和蛋白表达（吸光度（A）值）（0．230±0．036，0．275±0．039）较对照组（0．174±0．029，0．102±0．015）增强（均P〈0．01），蛋白质表达增高更明显。COPD组肺小血管PHD1 mRNA表达（0．180±0．030）与对照组（O．191±0．029）比无明显改变（P〉0．05）。COPD组PHD2、PHD3mRNA表达（0．245±0．044，0．252±0．023）较对照组（0．182±0．028，0．127±0．017）明显增高（均P〈0．01）。PHD1蛋白质表达（0．104±0．015）较对照组（0．209±0．023）降低（P〈0．01）。PHD2蛋白质表达（0．274±0．044）较对照组（0．219±0．043）增高（P〈0．01）。PHD3蛋白质表达（0．161±0．023）较对照组（0．1464-0．021）略增高，但差异无统计学意义（P〉0．05）。两组间FIHmRNA和蛋白质表达差异均无显著性（P〉0．05）；③相关分析表明HIF-1α蛋白质水平与WA％，PAMT及PHD2、PHD3mRNA及PHD2蛋白质呈正相关，与PHDl蛋白质呈负相关。结论：PHDs可能通过调节HIF-1α表达参与COPD患者的肺血管重塑。

英文摘要：

Objective： To observe the expression of hypoxia-inducible factor-1α subunit （HIF-1α）, HIF prolyl hydroxylase domain-containing protein（PHDs） and factor inhibiting HIF-1 （FIH） in pulmonary arteries of patient with chronic obstructive pulmonary disease （COPD）. Methods： Pulmonary specimens were obtained from patients undergoing lobectomy for lung cancer, 12 had concurrent COPD （ COPD group） and 14 without COPD （control group）. The ratio of vascular wall area to total vascular area （WA%） and pulmonary artery media thickness （PAMT） was observed, and HIF-1α and its hydroxylases（PHD1, PHD2, PHD3, FIH） mRNA and protein were detected by in situ hybridization and immunohistochemistry respectively. Results： WA% and PAMT of COPD patients（50μm ± 9 μm, 40% ± 5%, were statistically different from those of the control subjects （39μm ± 6μm, 31% ± 4 % P 〈 0.01 ）. Relative quantification of mRNA and protein levels （ absorbance, A ） showed that H1F-la mRNA and protein levels in COPD group （0. 230 ± 0. 036,0. 275 ± 0. 039） were statistically higher than those of the control subjects （0. 174 ± 0.029, 0.102 ± 0.015, P 〈 0.01 ）, and that the protein level increased more markedly. PHD1 mRNA in COPD subjects （0. 180 ± 0.030） was comparable to that in control group（0. 191 ± 0.029, P 〉 0.05）; PHD2 and PHD3 mRNA levels in COPD （0. 245 ± 0. 044, 0. 252 ± 0. 023） were significantly higher than those in control group（0.182 ± 0. 028, 0.127 ± 0. 017, P 〈 0.01 ）. On the other hand, in COPD subjects PHD1 protein （0. 104 ± 0. 015） was significantly lower（ P 〈 0.01 ）, whereas PHD2 protein （0. 274 ± 0. 044） was significantly higher（ P 〈 0.01 ） than those in control group（0. 209 ± 0. 023, 0. 219 ± 0. 043）. As for PHD3 protein, no significant changes were observed between the two groups （0. 161 ± 0.023 in COPD, 0. 146 ± 0.02t in control, P 〉 0.05）. FIH mRNA and protein both showed no differences between the two gro