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

Cui Maoxiang, Chen Xiaoling, Huo Chunling, Hu Xiaojie, Ai Jie

Department of Pathophysiology,Institute of Basic Medical Sciences,Hebei Medical University.Shijiazhuang 050017,Hebei

Abstract

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 smoothmuscle 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.

Key words: connective tissue growth factor;remodeling;Pulmonary artery;bleomycin;fibrosis;lung;Rat

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Citing This Article：

Cui Maoxiang, Chen Xiaoling, Huo Chunling, Hu Xiaojie, Ai Jie. Expression of connective tissue growth factor in pulmonary artery at the early--stage of pulmonary fibrosis. Acta Physiol Sin 2008; 60 (4): 535-540 (in Chinese with English abstract).