Effect and mechanism of cucurbitacin B preventing sepsis-induced acute lung injury in mice
OBJECTIVE To investigate the preventive effect of cucurbitacin B(CB)on sepsis-induced acute lung injury(ALI)and its mechanism.METHODS The mice were divided into control group,model group,dexamethasone group(positive control,2 mg/kg),CB low-dose and high-dose groups(25,50 mg/kg).Each group was given relevant medicine intraperitoneally,once a day,for 3 consecutive days.Twenty-four hours after the last administration,those groups were given lipopolysaccharide(10 mg/kg)intraperitoneally to establish sepsis-induced ALI model(finally,8 mice per group were included in the experiment),except for control group.Twenty-four hours after medication,blood routine indicators(total white blood cell count,neutrophils count,lymphocytes count),lung function indicators(total lung resistance,pulmonary outflow resistance,lung dynamic compliance,peak expiratory flow rate,and maximum ventilation volume),dry wet ratio of lung tissue were measured in each group.The lung tissue level of myeloperoxidase(MPO),and the serum levels of tumor necrosis factor-α(TNF-α),interleukin 1β(IL-1β),IL-6,superoxide dismutase(SOD)and malondialdehyde(MDA)were all detected.The pathological changes of lung tissue were observed;immunohistochemistry was used to detect the positive expression of phosphorylation signal transducer and activator of transcription 3(p-STAT3)in the lung tissue.Western blot assay was used to detect the expressions of proteins related to IL-6/JAK2/STAT3 signaling pathway in the lung tissue.RESULTS Compared with control group,total pulmonary resistance,pulmonary flow resistance,dry wet ratio of lung tissue,the total white blood cell count,neutrophils count,lymphocytes count of whole blood,the lung tissue level of MPO and serum levels of MDA,IL-6,IL-1β and TNF-α,the p-STAT3 protein optical density value,the protein expressions of IL-6 and IL-6 receptor,and the phosphorylation levels of JAK2 and STAT3 protein were increased significantly in the model group(P＜0.01),while lung dynamic compliance,peak expiratory flow rate,maximum ventilation volume and serum level of SOD were decreased significantly(P＜0.05 or P＜0.01).Pulmonary tissue showed alveolar collapse and infiltration of inflammatory cells.Compared with the model group,the above indexes of mice were reversed significantly in dexamethasone group and CB groups(P＜0.05 or P＜0.01),the pathological damage of lung tissue was reduced.CONCLUSIONS CB can prevent sepsis-induced ALI by inhibiting the activity of IL-6/JAK2/STAT3 signaling pathway and relieving inflammatory reactions.
国家科技期刊平台
NSTL
万方数据
