结缔组织生长因子在肺纤维化初期肺动脉中的表达

本研究观察了博莱霉素(bleomycin,BLM)诱导肺纤维化初期肺动脉压、肺动脉壁Ⅰ、Ⅲ型胶原的含量以及肺动脉壁结缔组织生长因子(connective tissue growth factor,CTGF)免疫阳性表达和分布.用气管内一次性滴注BLM(5 mg/kg体重)的方法复制肺纤维化动物模型大鼠;用右心漂浮导管技术检测肺动脉压;用天狼星红胶原纤维特异染色和偏振光观察肺动脉Ⅰ、Ⅲ型胶原;用免疫组织化学法检测肺动脉壁CTGF表达.结果显示:滴注BLM后第14天,大鼠肺动脉压高于对照组大鼠(P<0.05);肺动脉主干和肺内动脉壁Ⅰ、Ⅲ型胶原的染色面积大于对照组大鼠(P<0.05,P<0.01),肺动脉主干血管壁Ⅰ、Ⅲ型胶原染色面积的比值高于对照组大鼠(P<0.05);肺动脉主干和肺内动脉壁CTGF免疫染色面积均大于对照组大鼠,平均光密度也高于对照组大鼠(均P<0.05);增多的CTGF免疫阳性细胞主要分布在肺动脉的平滑肌层和内皮层.以上结果表明,在BLM致肺纤维化形成初期肺动脉高压和肺血管壁结构重塑过程中,肺动脉壁平滑肌层和内皮层CTGF表达增多,这可能是肺动脉高压维持和发展的机制之一.

Expression of connective tissue growth factor in pulmonary artery at the early-stage of pulmonary fibrosis

To ascertain whether connective tissue growth factor (CTGF) participates in the remodeling of pulmonary artery at the early-stage of bleomycin (BLM)-induced pulmonary fibrosis, mean pulmonary arterial pressure, the expression of type I and type III collagens, and the expression and location of CTGF in pulmonary artery and arteriole were investigated in the present study. Sprague-Dawley rats received instillation of BLM 5 mg/kg body weight, in 0.5 mL of normal saline (NS)] or instillation of the same amount of NS as control. Mean pulmonary arterial pressure was detected via a catheter in the pulmonary artery. Type I and type III collagens were examined with Sirius red staining under polarized light. CTGF expression was investigated by using immunohistochemistry, and was represented as average optical density and percentage of positive area of CTGF. The mean pulmonary arterial pressure was higher in rats on day 14 after BLM instillation (19.5+/-2.9) mmHg] than that in the control rats (14.8+/-1.2) mmHg] (P<0.05). The type I and type III collagens were increased both in pulmonary artery and arteriole of rats on day 14 after BLM instillation, compared with those in the control rats (P<0.05, P<0.01, respectively). The ratio of type I/III collagens in pulmonary artery was also higher in BLM-treated rats than that in the control rats (P<0.05). The values of average optical density of positive CTGF staining were increased both in pulmonary artery (0.37+/-0.02) and arteriole (0.40+/-0.03) of rats on day 14 after BLM instillation, compared with those in the control rats (artery, 0.34+/-0.01; arteriole, 0.29+/-0.01) (both P<0.05). The percentages of positive area of CTGF were higher in pulmonary artery (8.40+/-1.13) and arteriole (12.4+/-2.0) of rats on day 14 after BLM instillation than those in the control rats (artery: 1.42+/-0.63; arteriole: 1.16+/-0.34), respectively (both P<0.05). The increased positive CTGF staining areas were mainly located in the endothelium and smooth muscle layer. It is therefore concluded that CTGF expression increases in the endothelium and smooth muscle layer of pulmonary artery and arterioles during high pulmonary arterial pressure and remodeling of pulmonary artery at the early-stage of BLM-induced pulmonary fibrosis, and that the increased CTGF might be one of the mechanisms of maintenance and development of pulmonary hypertension.