慢性阻塞性肺疾病患者肺小血管低氧诱导因子-α的表达

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(HIF)-α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,诊断符合COPD者入选COPD组(12例),不符合者入选对照组(10例)。取2组患者的肺组织,原位杂交和免疫组化检测HIF-1α、HIF-2α、HIF-3α的mRNA及蛋白表达水平。光学显微镜观察并计算肺小动脉管壁厚度与外径的比值(WT%)及肺小动脉管壁面积与血管总面积的比值(WA%)。结果(1)COPD组WT%、WA%均较对照组高(P值均小于0·01)。(2)HIF-1αmRNA和蛋白表达在COPD组增强,吸光度(A)值分别为0·172±0·011、0·089±0·013,与对照组(0·103±0·010、0·042±0·010)比较差异有统计学意义(P值均小于0·01)。HIF-2αmRNA及蛋白表达在COPD组呈弱阳性,A值分别为0·038±0·010、0·077±0·010,与对照组(0·133±0·017、0·169±0·010)比较差异有统计学意义(P值均小于0·01)。HIF-3α仅mRNA表达在COPD组呈弱阳性,A值为0·077±0·010,与对照组(0·088±0·010)比较差异有统计学意义(P<0·05)。(3)相关分析HIF-1αmRNA及蛋白表达与WT%和WA%分别呈正相关,而HIF-2αmRNA及蛋白表达与WT%和WA%分别呈负相关,HIF-3αmRNA及蛋白表达与WT%和WA%均无相关性。结论COPD患者HIF-α基因表达有差异,此差异可能参与了COPD的肺血管重塑。

The expression of capillary hypoxia-induced factor-alpha and pulmonary artery remodeling in chronic obstructive pulmonary disease

OBJECTIVE: To observe the expression of hypoxia-inducible factor-alpha (HIF-1alpha, HIF-2alpha, HIF-3alpha) and pulmonary vascular remodeling in pulmonary arteries of patients with chronic obstructive pulmonary disease (COPD). METHODS: Pulmonary specimens were obtained from patients undergoing lobectomy for lung cancer, of whom 12 had concurrent COPD and 10 without COPD. Pulmonary vascular remodeling was observed with optical microscope, and HIF-alpha mRNA and protein were detected by in situ hybridization and immunohistochemistry respectively. RESULTS: Vascular remodeling parameters (WT%, WA%) of COPD patients [(24 +/- 3)%, (48 +/- 6)%, respectively] were statistically different from those of the control subjects [(15 +/- 2)%, (39 +/- 4)%, respectively]. Relative quantification of mRNA and protein levels (absorbance, A) showed that HIF-1alpha in COPD group (0.172 +/- 0.011, 0.089 +/- 0.013, respectively) were statistically higher than those of the control subjects (0.103 +/- 0.010, 0.042 +/- 0.010, P < 0.01). Furthermore, they correlated positively with the parameters for vascular remodeling. The mRNA and protein levels of HIF-2alpha in COPD group (0.038 +/- 0.010, 0.077 +/- 0.010, respectively) were significantly lower than those of the control subjects (0.133 +/- 0.017, 0.169 +/- 0.010, respectively, P < 0.01), and correlated negatively with the parameters for vascular remodeling. Regarding HIF-3alpha, only the mRNA level in COPD group (0.077 +/- 0.010) was statistically lower than that of the control subjects (0.088 +/- 0.010) (P < 0.05), and no correlation with vascular remodeling parameters was observed. CONCLUSIONS: Pulmonary vascular remodeling in COPD patients was accompanied by the differential expression of HIF-alpha gene, which may be involved in the process of hypoxic pulmonary vascular remodeling in COPD.