Membrane and Subcellular Muscle Injury Are Induced by Single or Multiple Exposure to Cigarette Smoke

作     者：Ana Maria Fleig-Mayer Alba Ramirez-Sarmiento Amanda Iglesias Montserrat Morla Carlos Coronell Diego Rodríguez Simona Pichinni Josep Lloreta Piergiorgio Zuccaro Xavier Busquets Joaquim Gea Jose R.Jardim Mauricio Orozco-Levi 

作者机构：Centro Universitario do Triangulo(UNITRI)Avenida nicomedes Alves Dos Santos4545-GaveaUberlandiaPulmonary Rehabilitation CenterRespiratory DivisionFederal University of Sao PauloSao PauloBrazil Group of Research in InjuryImmune Response and Function(LIF)Municipal Institute of Medical Research(IMIM)Carrer Dr.Aiguader 88BarcelonaE-08003Spain Servei de PneumologiaHospital del MarPasseig Maritim 25BarcelonaE-08003Spain Centro en Red de Investigacion de Enfermedades Respiratorias(CIBERES)Recinto Hospital Joan March Carretera Soller Km.1207110BunyolaMallorcaIlles BalearsSpain Institut Universitari d’Investigacio en Ciencies de la Salut(IUNICS)and Department de BiologiaUniversitat Illes Balears(UIB)Cra de ValldemossaKm 7.5PalmaIlles BalearsSpain Laboratorio Di Biochimica ClinicaIstituto Superiore Di Sanita.Viale Regina Elena 29900161RomaItaly Respiratory DepartmentFundacion Cardiovascular de ColombiaCalle 155A 23-58FloridablancaSantanderColombia Servei d’Anatomia PatologicaHospital del MarPasseig Maritim 25BarcelonaE-08003Spain 

出 版 物：《Open Journal of Pathology》 (病理学期刊（英文）)

年 卷 期：2014年第4卷第3期

页      面：125-137页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：PLAN DE FORTALECIMIENTO INSTITUCIONAL Ref.477-2012 y Ref.734-2013 Proyecto Exencion de Impuestos,COLCIENCIAS ref.contrato 656624037813-2013 Red Respira(RTIC C03/11,Fondo de Investigacion Sanitaria,Instituto de Salud Carlos III),SEPAR,Ministerio de Educacion,Cultura y Deporte de Espana 

主　　题：Skeletal Muscle Muscle Injury Muscle Regeneration Quadriceps Cigarette Smoking 

摘      要：Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD). Diaphragm injury is observed in patients with COPD. However, the potential role of smoking in triggering or perpetuating muscle injury is unknown. The present study was aimed at evaluating the potential role of commercial tobacco smoke as a direct cause of skeletal muscle injury in experimental conditions. Seventy Wistar rats (170 - 250 g) were assigned to smoking (n = 49) or non-smoking (n = 21) groups. The smoking groups were submitted to a single or multiple (i.e., five or thirty) daily sessions of cigarette smoking in an inhalatory chamber (time length: 2 h each session). The level of exposure was constant and assessed by CO concentrations (50 ppm) and serum cotinine analysis. Animals submitted to a single smoke exposure and the corresponding controls were euthanized in groups at 0 h, 2 h, 4 h, 24 h or 48 h after completing the exposure. Animals submitted to multiple exposures were euthanized at 0 h after smoking. Samples from vastus lateralis muscle were obtained and processed for assessing cell injury and selected protein expression. Monoclonal anti-albumin antibodies were used to identify muscle fibers with sarcolemmal (membrane) injury. Subcellular muscle injury was assessed using transmission electron microscopy (EM). MyoD, myogenin and α-tubulin were immunodetected using western blot techniques. Exposure to cigarette smoke associated with significant membrane damage (mean relative difference (MRD) with controls: +181%, p = 0.004) and sarcomere disruptions (MRD: +226%, p = 0.001). Expression of MyoD and myogenin (normalized to α-tubulin) were significantly increased at 4 h and remained increased at 48 h post-exposure. We conclude that not only a single but also consecutive exposure to tobacco smoke have acute deleterious effects on peripheral muscle structure. A rapid induction of subrogate markers of skeletal muscle stress and repair processes associates to sarcolemmal and