Participação do estresse oxidativo na lesão pulmonar induzida por lipopolissacarídeo: repercussões inflamatórias estruturais e funcionais

• Autor(a) principal: Trajano, Eduardo Tavares Lima
• Data de Publicação: 2011
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/7818
• topic: Lipopolysaccharide. Acute lung injury. Oxidative stress; Lipopolissacarídeo; Lesão pulmonar aguda; Estresse oxidativo; CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA

The aim of this study was to investigate the involvement of oxidative stress in acute lung injury (ALI) induced by lipopolysaccharide (LPS) and inflammatory effects, structural and functional, through biochemical analysis of oxidative stress, pulmonary function test, histological and RT-PCR for cytokines and transcription factors pro-inflammatory. In the first stage were used C57BL6 male mice were divided into seven groups: control group (CTR) (50 μL saline) administered via intratracheal [it], LPS 6 hours (10 μL of LPS) [it], LPS 12 hours (10 μL of LPS) [it], LPS 24 hours (10 μL of LPS) [it], LPS 48 hours (10 μL of LPS). To confirm that the observed changes were dependent on oxidative stress in C57BL6 male mice were pretreated with N-acetylcysteine (NAC) 1 hours before stimulation with LPS and sacrificed 24 hours after stimulation with LPS. The animals were divided as follows: LPS group 24 hours (10 μL) [it], NAC group 40 mg / kg (gavage) + LPS (10 μL) [it] NAC group and 100 mg / kg (gavage) + LPS (10 μL) [it]. The enzymatic antioxidant system protected the lungs against oxidative stress in the first 12 hours. Oxidative stress was characterized in 24 hours and 48 hours there was failure of the enzymatic antioxidant system. Pulmonary function parameters were shown in the altered group stimulated with LPS mainly in the LPS group. Elastance (p <0,001), peripheral airway resistance (ΔP2) (p <0,001), central airway resistance (ΔP1) (p <0,001) and total airway resistance (ΔPtot) (p <0,001) if especially in the group showed altered LPS 24 hours. Pretreatment with NAC prevented the increase in elastance parameters (p <0,001), peripheral airway resistance (ΔP2) (p <0,001) central airway resistance (ΔP1) (p <0,05) and resistance total airway (ΔPtot) (p <0,001) compared with the LPS group 24 hours. Histological changes such as thickening of alveolar septa, inflammatory cells and hemorrhage proved to be time dependent. The NAC pretreatment prevented the changes observed in the group stimulated with LPS. Inflammatory changes were observed in the group stimulated with LPS and IL-6 (p <0,001), iNOS (p <0,001), COX2 (p <0,05), TNF-α (p <0,001) and NFκB (p <0,001) compared with the control group. Pretreatment with NAC prevented the increase of these parameters as IL-6 (p <0,001), iNOS (p <0,001), COX2 (p <0,05), TNF-α (p <0,05) and NFκB ( p <0,001) when compared with LPS 24 hours. Our results suggest that oxidative stress plays an important role in inflammatory responses, structural and functional model of ALI induced by LPS and that these changes are dependent oxidative stress.