RESUMO
Inhibiting reactive oxygen species (ROS) has been viewed as a therapeutic target for the treatment of acute lung injury (ALI). Osthole, an active component in Chinese herbal medicine, has drawn increasing attention because of its various pharmacological functions, including anti-inflammatory and anti-oxidative activities. The aim of the present study was to examine the effects of osthole on ALI induced by lipopolysaccharide (LPS) through intratracheal instillation. The mRNA and protein expression levels of thioredoxin 1 (Trx1) and the nuclear factor erythroid-2 related factor 2 (Nrf2) were detected by real-time PCR, reverse transcription PCR (RT-PCR) and Western blot, respectively. ROS production was measured by flow cytometry. Our results showed that osthole treatment improved the mice survival rates in the middle and high dosage groups, compared with the untreated LPS group. Moreover, osthole treatment significantly improved LPS-induced lung pathological damage, and it decreased the lung injury scores, lung wet/dry ratios and the total protein level in Bronchoalveolar lavage fluid (BALF). Osthole treatment dramatically reduced the H2O2, MDA and OH levels in the lung homogenates. LDH and ROS were markedly reduced in the osthole+LPS group in vitro. Furthermore, osthole increased Nrf2 and Trx1 expression in terms of mRNA and protein in vivo and in vitro. Nrf2 siRNA (siNrf2) could suppress the beneficial effects of osthole on ALI. In conclusion, the current study demonstrates that osthole exerted protective effects on LPS-induced ALI by up-regulating the Nrf-2/Trx-1 pathway.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cumarínicos/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Tiorredoxinas/metabolismo , Regulação para Cima/efeitos dos fármacos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/mortalidade , Animais , Líquido da Lavagem Broncoalveolar , Bloqueadores dos Canais de Cálcio/farmacologia , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/genética , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estatísticas não Paramétricas , Análise de Sobrevida , Tiorredoxinas/genética , Fatores de Tempo , TransfecçãoRESUMO
Matrine is one of the main active components of Chinese herb Sophora flavescens Ait (Kushen), which has been demonstrated to be effective in suppressing inflammation. The aim of the present study is to investigate the effect of matrine on LPS-induced lung injury. Lung injury was assessed by histological study and wet to dry weight ratios, as well as cell count and protein content in bronchoalveolar lavage fluid. We also detected MPO activity reflecting neutrophil infiltration and MDA activity examining oxidative stress in lung tissues. Cytokines and ROS production in cells were monitored by ELISA and flow cytometry, respectively. The results showed that high dose of matrine significantly reduced the mortality rate of mice with LPS administration. Treatment with matrine improved LPS-induced lung histopathologic changes, alleviated pulmonary edema and lung vascular leak, inhibited MPO and MDA activity,and reduced the production of inflammatory mediators including TNF-α, IL-6 and HMGB1. In vitro, matrine administration reduced the production of ROS and inflammatory factors, which was possibly associated with inhibition of NF-κB. In conclusion, the current study demonstrated that matrine exhibited a protective effect on LPS-induced acute lung injury by inhibiting of the inflammatory response, which may involve the suppression of ROS and tissue oxidative stress.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Alcaloides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , NF-kappa B/metabolismo , Quinolizinas/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Alcaloides/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Líquido da Lavagem Broncoalveolar , Linhagem Celular , Proteína HMGB1/metabolismo , Interleucina-6/metabolismo , Contagem de Leucócitos , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Malondialdeído/metabolismo , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , Quinolizinas/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , MatrinasRESUMO
Relieving pulmonary edema is the key of a successful treatment to seawater drowning. Sodium tanshinone IIA sulfonate (STS) has been observed to reduce lung edema from lipopolysaccharide (LPS)-induced lung injury. In this study the authors investigated whether STS attenuates seawater aspiration-induced acute pulmonary edema, and examined the effects of sodium-potassium adensosine triphosphatase (Na(+),K(+)-ATPase) on it. Seawater was instilled through an endotracheal tube. The anesthetized and spontaneously breathing rats received STS intraperitoneally after seawater aspiration. Pao(2), lung wet-to-dry weight ratio, and pulmonary microvascular permeability were tested. The authors explored the effects of STS on the expression and activity of Na(+),K(+)-ATPase in vivo and in vitro. Additionally, the authors investigated the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway in the stimulation of Na(+),K(+)-ATPase by STS. The results showed that STS significantly improved hypoxemia, attenuated lung edema, and alleviated seawater-induced lung injury in vivo. Both in vivo and in vitro, it was observed that STS up-regulated the expression and activity of Na(+),K(+)-ATPase. ERK1/2 inhibitor partially blocked the effects of STS on Na(+),K(+)-ATPase activity in alveolar type II cells following seawater incubation. These results indicated that STS could improve seawater aspiration-induced acute pulmonary edema by up-regulating Na(+),K(+)-ATPase activity, and the ERK1/2 signaling pathway may be involved in it.