s19 3毒物应用药理学2005 20327.pdfVIP

Toxicology and Applied Pharmacology 203 (2005) 27 35 cate/ytaap Cell-specific modulation of surfactant proteins by ambroxol treatment Carola Seifart*, Ursula Clostermann, Ulf Seifart, Bernd Mqller, Claus Vogelmeier, Peter von Wichert, Heinz Fehrenbach Department of Internal Medicine, Division of Respiratory Medicine, Philipps-University of Marburg, 35043 Marburg, Germany Received 5 May 2004; accepted 21 July 2004 Available online 2 October 2004 Ambroxol [trans 4 (2 amino 3,5 dibromobenzylamino) cyclohexanole hydrochloride], a mucolytic agent, was postulated to provide surfactant stimulatory properties and was previously used to prevent surfactant deficiency. Currently, the underlying mechanisms are not exactly clear. Because surfactant homeostasis is regulated by surfactant specific proteins (SP), we yzed protein amount and mRNA expression in whole lung tissue, isolated type II p ocytes and bronchoalveolar lavage of Sprague Dawley rats treated with ambroxol i.p. (75 mg/kg body weight, twice a day [every 12 h]). The methods used luded competitive polymerase chain reaction (RT PCR), Northern blotting, Western immunoblotting, and immunohistochemistry. In isolated type II p ocytes of ambroxol treated animals, SP C protein and mRNA content were reased, whereas SP A, B and D protein, mRNA, and immunoreactivity remained unaffected. However, ambroxol treatment resulted in a signific crease of SP B and in a