Li Qi-fang, Dai Ai-guo, Xu Ping
Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha 410001, China.
Zhonghua Nei Ke Za Zhi. 2006 Feb;45(2):136-9.
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).
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.
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.
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.
观察慢性阻塞性肺疾病(COPD)患者肺动脉中缺氧诱导因子-α(HIF-1α、HIF-2α、HIF-3α)的表达及肺血管重塑情况。
从因肺癌行肺叶切除术的患者获取肺标本,其中12例合并COPD,10例不合并COPD。用光学显微镜观察肺血管重塑情况,分别通过原位杂交和免疫组织化学检测HIF-α mRNA和蛋白。
COPD患者的血管重塑参数(WT%、WA%)[分别为(24±3)%、(48±6)%]与对照组[分别为(15±2)%、(39±4)%]相比有统计学差异。mRNA和蛋白水平的相对定量(吸光度,A)显示,COPD组中HIF-1α(分别为0.172±0.011、0.089±0.013)在统计学上高于对照组(0.103±0.010、0.042±0.010,P<0.01)。此外,它们与血管重塑参数呈正相关。COPD组中HIF-2α的mRNA和蛋白水平(分别为0.038±0.010、0.077±0.010)显著低于对照组(分别为0.133±0.017、0.169±0.010,P<0.01),且与血管重塑参数呈负相关。关于HIF-3α,仅COPD组的mRNA水平(0.077±0.010)在统计学上低于对照组(0.088±0.010)(P<0.05),且未观察到与血管重塑参数相关。
COPD患者的肺血管重塑伴随着HIF-α基因的差异表达,这可能参与了COPD中缺氧性肺血管重塑的过程。