Yu Wen-Cheng, Guo Cai-Hong
Department of Respiratory, Medical School Hospital of Qingdao University, Qingdao 266003, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2007 Sep;30(9):657-61.
To investigate the apoptosis versus proliferation activities of pulmonary artery smooth muscle cells (PASMC) in pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD) and pulmonary vascular structural remodeling.
Forty-five patients were divided into three groups: patients without COPD and PH (non-COPD group, n = 15), COPD patients without PH (COPD with non-PH group, n = 15) and patients with PH associated with COPD (COPD with PH group, n = 15). Lung tissue samples were obtained from surgically resected specimens. The remodeling of pulmonary arteries were observed under microscope, and the changes of morphology-the ratio of the thickness of the wall to the external diameter of the pulmonary arterioles (WT%) and the ratio of the area of the wall to that of the pulmonary arterioles (WA%) were analyzed by computer-based image analysis system. The proliferation of PASMC was detected by proliferating cell nuclear antigen (PCNA) with immunohistochemical technique, and TUNEL (terminal deoxynu-cleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling) was used for the detection of the apoptosis of PASMC.
In the COPD with non-PH group, the arterial walls were thicker and the lumens narrower than that of the non-COPD group. In the COPD with PH group, the walls were thicker and the lumens narrower than that of the COPD with non-PH group. In the COPD with non-PH group and the COPD with PH group, the WT% and WA% [(20 +/- 4)% and (35 +/- 5)%; (28 +/- 5)% and (50 +/- 6)%, respectively] were higher than those of the non-COPD group (16 +/- 3)% and (25 +/- 3)% (P < 0.01), and the WT% and WA% of the COPD with PH group were higher than those of the COPD with non-PH group (P < 0.01). Both proliferative and apoptotic PASMC were found in the patients of the three groups. The proliferation indexes (PI) of the COPD with non-PH group and the COPD with PH group [(19 +/- 5)% and (38 +/- 7)%] were significantly higher than that of the non-COPD group [(8 +/- 2)%, P < 0.01], while the apoptosis indexes (AI) [(4.5 +/- 1.3)% and (3.1 +/- 1.3)%] were lower than that of the non-COPD group [(6.9 +/- 1.9)%, P < 0. 01]. The PI of the COPD with non-PH group was lower than that of the COPD with PH group; the AI was higher than that of the COPD with PH group (P < 0.05). The PaO(2) of the COPD with non-PH group and the COPD with PH group was negatively related with the PI (r = -0.519, P = 0.003), but positively related to the AI of the PASMC (r = 0.441, P = 0.015).
The imbalance of the increased proliferation and decreased apoptosis of PASMC may contribute to the pulmonary vascular structural remodeling and pulmonary arterial hypertension in patients of COPD. Hypoxia is one of the main causes of increased proliferation and decreased apoptosis of the PASMC.
研究慢性阻塞性肺疾病（COPD）相关肺动脉高压（PH）患者中肺动脉平滑肌细胞（PASMC）的凋亡与增殖活性以及肺血管结构重塑情况。
45例患者分为三组：无COPD和PH的患者（非COPD组，n = 15）、无PH的COPD患者（COPD无PH组，n = 15）和COPD相关PH患者（COPD伴PH组，n = 15）。肺组织样本取自手术切除标本。在显微镜下观察肺动脉重塑情况，并用计算机图像分析系统分析形态学变化——肺小动脉壁厚度与外径之比（WT%）以及壁面积与肺小动脉面积之比（WA%）。采用免疫组织化学技术通过增殖细胞核抗原（PCNA）检测PASMC的增殖情况，并用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记法（TUNEL）检测PASMC的凋亡情况。
COPD无PH组的动脉壁比非COPD组更厚，管腔更窄。COPD伴PH组的动脉壁比COPD无PH组更厚，管腔更窄。COPD无PH组和COPD伴PH组的WT%和WA%[分别为(20±4)%和(35±5)%；(28±5)%和(50±6)%]高于非COPD组（16±3)%和(25±3)%（P<0.01），且COPD伴PH组的WT%和WA%高于COPD无PH组（P<0.01）。三组患者中均发现有增殖和凋亡的PASMC。COPD无PH组和COPD伴PH组的增殖指数（PI）[分别为(19±5)%和(38±7)%]显著高于非COPD组[(8±2)%，P<0.01]，而凋亡指数（AI）[(4.5±1.3)%和(3.1±1.3)%]低于非COPD组[(6.9±1.9)%，P<0.01]。COPD无PH组的PI低于COPD伴PH组；AI高于COPD伴PH组（P<0.05）。COPD无PH组和COPD伴PH组的PaO₂与PI呈负相关（r = -0.519，P = 0.003），但与PASMC的AI呈正相关（r = 0.441，P = 0.015）。
PASMC增殖增加而凋亡减少的失衡可能导致COPD患者肺血管结构重塑和肺动脉高压。缺氧是PASMC增殖增加和凋亡减少的主要原因之一。
