Inhalation of aminoguanidine prevents the up-regulation of connective tissue growth factor in fibrotic lungs of rats / 生理学报

ABSTRACT

Connective tissue growth factor (CTGF) is a known profibrotic cytokine. The purpose of the present study was to explore the effects of inhalation of aminoguanidine (AG) on the up-regulation of CTGF in fibrotic lungs of rats. Sprague-Dawley rats received single intratracheal instillation of bleomycin (BLM) or instillation of the same volume of normal saline (NS) as control. From day 1 to day 30 after intratracheal BLM instillation, the rats inhaled AG (2, 10 or 50 mmol/L, 5 min each time) twice a day or inhaled the same volume of NS as vehicle control. The change of nitric oxide (NO) content in lungs was evaluated by nitrite/nitrate (NO₂(-)/NO₃(-)) content in out-flowing pulmonary plasma (OPP). The degree of fibrosis in lung was evaluated by the content of hydroxyproline (chloramine T method) and area of collagen (Masson stain) in lung. The CTGF expression in lung was detected by Western blot and RT-PCR. The contents of NO₂(-)/NO₃(-) were increased in OPP of rats on day 14 after the instillation of BLM, compared with those in the rats with instillation of NS [(156+/-21) mumol/L vs (51+/-15) mumol/L, P<0.01]. The content of hydroxyproline, the area of collagen, and the levels of CTGF protein and mRNA were increased in lungs of rats on day 30 after intratracheal instillation of BLM, compared with those in the rats with instillation of NS [hydroxyproline, (51+/-10) mg/g lung vs (20+/-5) mg/g lung; area of collagen, (38.7+/-8.8)% vs (5.7+/-1.5)%; CTGF protein, (1+/-0.25) vs (0.3+/-0.1); CTGF mRNA, (0.8+/-0.2) vs (0.15+/-0.03), P<0.01]. The above-mentioned indices were ameliorated by the inhalation of AG (10 or 50 mmol/L) (NO₂(-)/NO₃(-) content, P<0.01; other indices, P<0.05). It is therefore concluded that the inhalation of AG prevented the up-regulation of CTGF in fibrotic lungs of rats suffering from BLM instillation, which might be one of the mechanisms of the anti-fibrosis of AG in lungs.