Tian Feng, Xu Yong-jian, Zhang Zhen-xiang, Hu Jing
Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhonghua Nei Ke Za Zhi. 2007 Apr;46(4):298-301.
To study the relation between connective tissue growth factor (CTGF) expression of pulmonary arteries and pulmonary arteries remodeling in smokers and in chronic obstructive pulmonary disease (COPD) patients.
Pulmonary tissues removed for lung cancer from 24 patients were assigned into non-smoker control group (N), smoker group (S), smoker and COPD group (S + C), 8 subjects each group. The specimen were obtained far from the cancer focus (>5 cm). Pulmonary arterial remodeling was observed by hematoxylin-eosin staining, and collagen contents of pulmonary artery wall were measured by sirius red staining and picro-polarization method. Immunohistochemistry was used to determine the proliferating cell nuclear antigen (PCNA) and CTGF protein expression of pulmonary artery smooth muscles. The CTGF mRNA expressions of pulmonary arteries were evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). The difference between the groups was analyzed.
(1) The percent of pulmonary artery wall area to total area (WA%) of the three groups were (28.4 +/- 4.7)%, (46.3 +/- 3.5)% and (55.5 +/- 3.9)%, respectively. Compared to the control group, there was a significant increase in the S and the S + C groups (P < 0.01). (2) The collagen thickness of pulmonary arteries was (6.4 +/- 1.6) microm, (15.9 +/- 2.4) microm and (16.4 +/- 2.3) microm, respectively. Collagen was abnormally increased and deposited in pulmonary artery walls of the S and the S + C groups (P < 0.01). (3) CTGF mRNA expressions of pulmonary artery walls were 0.095 +/- 0.015, 0.396 +/- 0.167 and 0.501 +/- 0.177, respectively. Compared to the control group, there was a significant increase in the S and the S + C groups (P < 0.01). (4) PCNA expressions of pulmonary artery walls were 0.084 +/- 0.006, 0.178 +/- 0.018 and 0.226 +/- 0.134, respectively; the expressions of the S and the S + C groups were significant increased as compared to the control group (P < 0.01). (5)CTGF protein expressions of pulmonary artery walls were 0.085 +/- 0.011, 0.245 +/- 0.095 and 0.303 +/- 0.191, respectively; compared to the control group, there was a significant increase in the S and the S + C groups (P < 0.01). (6) Both CTGF mRNA and protein expression of pulmonary arteries were positively correlated with WA% (r = 0.915, P < 0.01; r = 0.919, P < 0.01). Similarly, both CTGF mRNA and protein expression of pulmonary arteries were positively correlated with PCNA expression (r = 0.938, P < 0.01; r = 0.928, P < 0.01).
Pulmonary artery remodeling is evident in smokers without COPD, but the remodeling became more severe in patients with COPD. Increased expression of CTGF may play an important role in pulmonary artery remodeling.
研究吸烟者及慢性阻塞性肺疾病(COPD)患者肺动脉中结缔组织生长因子(CTGF)表达与肺动脉重塑之间的关系。
将24例因肺癌切除的肺组织患者分为非吸烟对照组(N)、吸烟组(S)、吸烟合并COPD组(S + C),每组8例。标本取自距癌灶较远(>5 cm)处。采用苏木精-伊红染色观察肺动脉重塑,用天狼星红染色和偏振光显微镜法测量肺动脉壁胶原含量。采用免疫组织化学法检测肺动脉平滑肌中增殖细胞核抗原(PCNA)和CTGF蛋白表达。通过逆转录聚合酶链反应(RT-PCR)评估肺动脉CTGF mRNA表达。分析组间差异。
(1)三组肺动脉壁面积占总面积的百分比(WA%)分别为(28.4±4.7)%、(46.3±3.5)%和(55.5±3.9)%。与对照组相比,S组和S + C组显著增加(P < 0.01)。(2)肺动脉胶原厚度分别为(6.4±1.6)μm、(15.9±2.4)μm和(16.4±2.3)μm。S组和S + C组肺动脉壁胶原异常增加并沉积(P < 0.01)。(3)肺动脉壁CTGF mRNA表达分别为0.095±0.015、0.396±0.167和0.501±0.177。与对照组相比,S组和S + C组显著增加(P < 0.01)。(4)肺动脉壁PCNA表达分别为0.084±0.006、0.178±0.018和0.226±0.134;S组和S + C组表达与对照组相比显著增加(P < 0.01)。(5)肺动脉壁CTGF蛋白表达分别为0.085±0.011、0.245±0.095和0.303±0.191;与对照组相比,S组和S + C组显著增加(P < 0.01)。(6)肺动脉CTGF mRNA和蛋白表达均与WA%呈正相关(r = 0.915,P < 0.01;r = 0.919,P < 0.01)。同样,肺动脉CTGF mRNA和蛋白表达均与PCNA表达呈正相关(r = 0.938,P < 0.01;r = 0.928,P < 0.01)。
无COPD的吸烟者肺动脉重塑明显,但COPD患者的重塑更严重。CTGF表达增加可能在肺动脉重塑中起重要作用。