Protective effect of esketamine on lung injury induced by hepatic ischemia-reperfusion in young mice models
Objective To investigate the protective effect and underlying mechanism of esketamine on the lung injury induced by hepatic ischemia-reperfusion(I-R)in young mice models.Methods Eighteen C57 young mice were randomly divided into three groups with 6 mice each.Group C was taken as sham operation.The hepatic I-R models were established by hepatic ischemia for 6 hours in groups of I-R and S.Group I-R was taken as the model control.Esketamine 10 mg/kg was injected via tail vein before hepatic I-R in group S.At the time of 6 hours after hepatic I-R in groups of I-R and S and 6 hours after abdominal clearance in group C,serum,bronchoalveolar lavage fluid(BALF)and lung tissues were collected.The pathological changes of lung tissues were observed by HE staining.The levels of serum high mobility group box-1 protein(HMGB1)and TNF-α and IL-1βin BALF were determined by ELISA.The concentration of malonaldehyde(MDA)and activity of superoxide dismutase(SOD)in the lung tissues were measured by thiobarbituric acid and hydroxylamine methods,respectively.The expression of HMGB1 in the lung tissues was analyzed by immunohistochemical staining.The protein expressions of PI3K,Akt and mammalian target of rapamycin(mTOR)in the lung tissues were dectected by Western blot.Results Compared with group C,the pathological injury of lung tissues was aggravated 6 hours after I-R,the expression of HMGB1 in the cytoplasm of lung tissues was increased,the levels of serum HMGB1 and TNF-α and IL-1β in BALF were elevated,the concentration of MDA was increased,the activity of SOD was decreased,and the protein expressions of PI3K,Akt and mTOR in the lung tissues were upregulated in group I-R(P<0.05).Compared with I-R group,all the above indicators in group S were improved(P<0.05).Conclusion The injection of esketamine before model establishment can obviously decrease the level of HMGB1 in the serum and lung tissues,downregulate the protein expressions of PI3K,Akt and mTOR,inhibit the release of IL-1β and TNF-α,alleviate oxidative stress reactions,which produces a protective effect on the lung injury in young mice I-R models.
EsketamineIschemia-reperfusionLung injuryHigh mobility group box-1 protein