Modulatory effect of silymarin on pulmonary vascular dysfunction through HIF-1 alpha-iNOS following rat lung ischemia-reperfusion injury

摘要

Silymarin is a traditional therapeutic used to protect the liver, acting to oppose lipid peroxidation, to enhance liver regeneration and functioning as an antioxidant. However, the effects of silymarin on pulmonary vascular dysfunction have not been investigated. In the present study, the modulatory effects of silymarin on pulmonary vascular dysfunction and the underlying mechanisms behind this were investigated in a lung ischemia-reperfusion (I/R) injury rat model. Male Sprague Dawley rats were randomly divided into 3 groups, including: i) A control group (n=10); ii) an I/R group (n=10); and iii) a silymarin-treated group (n=10). All experimental rats received 250 mg/kg/day of silymarin for 8 days. Silymarin was demonstrated to markedly improve lung I/R-induced pulmonary vascular dysfunction and lung moisture. Following silymarin treatment, inflammation and oxidative stress in the lung I/R-injury rats were demonstrably suppressed. Treatment with silymarin also inhibited the activation of caspase-3 and -9, and hypoxia inducible factor-1 alpha (HIF-1 alpha) and inducible nitric oxide synthase (iNOS) protein expression in the lung I/R-injury rats. Silymarin was concluded to impact upon pulmonary vascular dysfunction through the HIF-1 alpha-iNOS pathway in the lung I/R injury rat model.