Protective Effects Of Rosiglitazone On Pulmonary Inflammation And Oxidative Stress Induced By Lipopolysaccharide In Mice

Background Acute lung injury/acute respiratory distress syndrome(ALI/ARDS)is not uncommon in daily clinical work.Patients with acute lung injury are in a stable condition,and it is often necessary to take active and effective rescue measures for patients.However,there is still a lack of alternative medical treatments.Bacterial lipopolysaccharide(LPS)is not only a key substance in the pathogenicity of Gram-negative bacteria,but also the most important and one of the most common factors causing ALI/ARDS in real life.Rosiglitazone(RSG)is widely used in clinical activities,and it has the advantages of safety,low cost,convenience and easy availability.So far,in addition to being found to effectively reduce blood glucose,more and more studies have shown that RSG has the effect of inhibiting inflammation,so it has a wide application prospect in the treatment of respiratory diseases.However,there is still a lack of research on the mechanism of its protective effect in the ALI/ARDS process and its regulation at the molecular level.Objective The purpose of this study was to explore the possible mechanism of RSG preconditioning in reducing inflammation and oxidative stress in the process of ALI induced by LPS in mice.Methods The experimental mice were randomly divided into control group,rosiglitazone pretreatment group(RSG group),LPS exposure group(LPS 6h group)and LPS exposure group after rosiglitazone pretreatment group(RSG+LPS 6h group).LPS was exposed to a single dose of 2 mg/kg in the form of abdominal infection.Four consecutive days before acute exposure to LPS,mice were given intragastric administration of RSG at a dose of 10 mg/kg once a day.Six hours after acute exposure to LPS in the abdominal cavity,the cervical vertebrae were dislocated,collecting lung tissue of mice.HE staining and pathological score were used to evaluate the degree of pathological injury of lung tissue semi-quantitatively.The expression levels of inflammatory chemokine Keratinocyte-Derived Chemokine(KC)and proinflammatory factor Tumor Necrosis Factor-α(TNF-α)in lung tissue were detected by ELISA method,and the level of inflammation in lung tissue was quantitatively analyzed.The protein expressions of NADPH oxidase subunits NOX-2,NOX-4 and nuclear factor-kappa B(NF-κB)signaling pathways(IκBα,p-IκBα,p-p65)in lung tissue were measured with Western blotting method,while the effects of RSG on NF-κB pathway and oxidative stress were qualitatively analyzed.Results Compared with the simple LPS exposure group,RSG pretreatment could inhibit the increase of lung mass after LPS exposure and reduce the severity of lung tissue injury induced by LPS,but the effect on lung coefficient was not statistically significant.Compared with LPS group,the increase of KC and TNF-α in lung tissue induced by LPS in RSG pretreatment group was inhibited,and RSG pretreatment reduced the inflammatory level of lung tissue after LPS injury in mice.Compared with the non-preconditioning group,RSG pretreatment could down-regulate the phosphorylation levels of IκBα and NF-κB p65 subunits,and block the activation of NF-κB pathway in lung injury induced by LPS.RSG pretreatment hindered the up-regulation of NOX-4 expression in lungs caused by LPS damage and reduced the damage caused by oxidative stress.Although the effect of RSG pretreatment on NOX-2 expression was not statistically significant,it still had a significant inhibition trend.Conclusion In this study,the protective effect of RSG on ALI induced by LPS damage was discussed.The results showed that pretreatment with RSG could reduce ALI induced by LPS in mice.The protective effect of supplemental RSG on LPS-induced ALI in mice is mediated by inhibition of inflammation and oxidative stress in lung tissue.