前列环素在慢性阻塞性肺疾病患者肺组织中的表达

目的 研究前列环素在慢性阻塞性肺疾病患者肺组织中的表达变化.方法 分别采集湘雅二医院2008年6-10月因肺癌、肺大疱入院行肺叶切除术的患者22例的肺组织标本,分为COPD组(12例)和对照组(10例).采用缺口末端标记法定量测定肺血管内皮细胞凋亡,免疫组织化学法检测前列环素合酶(PGI_2-S)蛋白表达,酶联免疫吸附试验测定6-酮前列腺素F_(1α)含量变化.两组间比较采用t检验.结果 COPD组肺中型血管和微小型血管内皮细胞凋亡指数[(12.9±2.0)%和(11.4±1.4)%]明显高于对照组[(6.1±1.2)%和(5.9±0.4)%],PGI_2-S蛋白表达率[(55.2±9.8)%和(42.3±5.1)%]明显低于对照组[(95.4±2.1)%和(82.3±7.4)%],气道上皮细胞中PGI_2-S蛋白表达率[(31.8±5.2)%]明显低于对照组[(95.5±2.2)%],6-酮前列腺素F_(1α)含量[(2.6±0.4)μg/L]明显低于对照组[(16.2±2.8)μg/L],差异均有统计学意义(t值为9.6～173.6,均P<0.01).结论 COPD患者肺血管内皮细胞存在异常凋亡现象,PGI_2-S蛋白表达下降,肺组织中前列环素生成明显减少,这些变化可能是COPD患者肺血管内皮细胞功能异常的组织学标志,并参与COPD的发生与发展.

The expression of prostacyclin in lungs from patients with chronic obstructive pulmonary disease

Objective To investigate the expression of prostacyelin in lungs from patients with chronic obstructive pulmonary disease (COPD). Methods The lung tissues were obtained from 12 patients with COPD and 10 patients without COPD. The apoptosis of pulmonary vascular endothelial cells was analyzed quantitatively using TdT-mediated dUTP nick end labeling (TUNEL). The expression of PGI_2-S protein was assessed by immunohistochemistry of paraffin-embedded tissues. 6-keto Prostaglandin F_(1α), the stable metabolite of PGI_2, was measured by enzyme-linked immunosorbent assay in whole-lung tissue extracts. The data distributed normally were expressed as x±s, and the independent-samples t test was used for comparison of means. Results The apoptotic index (AI) of endothelial cells of medium and small-sized vessels in patients with COPD group [(12.9±2.0) %, (11.4±1.4)%] were significantly higher than that of patients without COPD [(6.1±1.2)%, (5.9±0.4)%]. In patients without COPD, PGI_2-S protein expression in medium vessels and small-sized vessels was (95.4±2.1) % and (82.3±7.4) % respectively, and the value was (95.5±2. 2)% in airway epithelial cells. In patients with COPD, PGI_2-S expression in medium vessels and small-sized vessels decreased remarkably [(55.2±9.8)% and (42.3± 5.1)% respectively], and exhibited a marked reduction in airway epithelial cells (31.8±5.2)%. The level of 6-keto Prostaglandin F_(1α) was significantly lower in patients with COPD (2.6±0.4)μg/L compared with patients without COPD (16.2±2.8)μg/L. Conclusions Abnormal apoptosis exists in pulmonary vascular endothelial cells in patients with COPD. In patients with COPD, the expression of PGI_2-S and the level of 6-keto Prostaglandin F_(1α) in lung tissues were decreased. The results suggest that abnormal apeptosis, reduction of PGI_2-S expression and PGI_2 may be important histological markers for pulmonary endothelial cell dysfunction in COPD and may be involved in the pathogenesis of the disease.