Nobiletin Alleviates LPS-induced Lung Injury via FOXO3a/SIRT1 Pathway
Objective To observe the role of nobiletin in sepsis-induced lung injury and explore its potential mechanism.Methods According to random number table,48male C57 BL/6mice aged 8-10 weeks were divided into 4groups,namely control group,lung injury group,treatment group(5mg/kg),and treatment group(10mg/kg),with 10mice in each group.The mice of control group did not receive any treatment;LPS(10mg/kg)was injected intraperitoneally in mice of lung injury group;the mice of treatment group(5mg/kg)received intraperitoneal injection of lipopolysaccharide(10mg/kg)and intragastric administration of nobiletin(5mg/kg);the mice of treatment group(10mg/kg)received intraperitoneal injection of lipopolysaccharide(10mg/kg)and intragastric adminis-tration of nobiletin(10mg/kg).After 12hours of intraperitoneal injection of lipopolysaccharide,the lung function and arterial blood gas of mice in each group were detected,and the lung tissue collected to evaluate the lung injury status and possible targets of mice from the pathological and molecular biological levels.Results Compared with the control group,the airway pressure,PaCO2 and lung injury score in the lung injury group were significantly increased,while PaO2 was significantly decreased(P<0.05);Compared with lung injury group,the airway pressure,PaCO2 and lung injury score in the treatment group(5mg/kg)and treatment group(10mg/kg)were signifi-cantly decreased,and PaO2 was significantly increased(P<0.05).Western blot showed that the protein expression levels of IL-1β,TNF-α,TXNIP and 4-HNE significantly increased in lung injury group(P<0.05);Compared with the lung injury group,the expres-sion levels of the above proteins in the lung tissue of mice in the treatment group(5mg/kg)and the treatment group(10mg/kg)were sig-nificantly decreased(P<0.05).In addition,the protein expression levels of FOXO3a and SIRT1 of mice in the lung injury group were significantly lower than those in control group(P<0.05);Compared with the lung injury group,the protein expression levels of FOXO3a and SIRT1 in the treatment group(5mg/kg)and the treatment group(10mg/kg)were significantly up-regulated(P<0.05).Conclusion Nobiletin can inhibit the lung injury in mice with sepsis by reducing oxidative stress and inflammatory reaction,and its mechanism may be related to the activation of FOXO3a/SIRT1 pathway.
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