Mechanism of curcumol in ameliorating lung injury and inducing apoptosis of alveolar macrophages in rats with severe acute pancreatitis via SIRT1/FOXO1 pathway
OBJECTIVE To investigate the ameliorative effect of curcumol on lung injury of severe acute pancreatitis(SAP)rats via the silent information regulator transcript 1(SIRT1)/forkhead transcription factor 1(FOXO1)pathway and its effect on alveolar macrophage apoptosis.METHODS Seventy-five rats were randomly divided into control group(normal saline),model group(normal saline),low-dose curcumol group(4 mg·kg-1 curcumol),high-dose curcumol group(16 mg·kg-1 curcumol),and antagonist group(16 mg·kg-1 curcumol+2 mg·kg-1 EX527)according to weight ranking method,15 rats in each group.The rat model of acute pancreatitis was established except the control group,which was then immediately administrated with the appropriate drug or saline by gavage and given once again after 12 hours.Rats were sacrificed after 72 hours.The serum amylase(AMS),endotoxin levels,lung tissue pathology scores,alveolar macrophage apoptosis rate,tumor necrosis factor-α(TNF-α)and nitric oxide(NO)levels in alveolar macrophages,and the expression of SIRT1,FOXO1,Ac-FOXO1 and nuclear factor-κB(NF-KB)p65 protein in alveolar macrophages were compared in each group.RESULTS Compared with those in the control group,the serum AMS level,endotoxin level,lung histopathological score,alveolar macrophage TNF-α and NO levels and NF-KB p65 protein relative expression level in the model group were significantly increased(P＜0.05).Compared with those in the model group,the above indexes in the low-dose curcumol group,high-dose curcumol group and antagonist group were signifi-cantly reduced(P＜0.05),and those in the high-dose curcumol group were lower than those in the low-dose curcumol group and antagonist group(P＜0.05).Compared with those in the control group,the apoptosis rate of alveolar macrophages and the rela-tive expression of SIRT1 and Ac-FOXO1 protein in the alveolar macrophages in the model group decreased(P＜0.05).Com-pared with those in the model group,the above indexes of the low-dose curcumol group,high-dose curcumol group and antagonist group increased(P＜0.05),and those in the high-dose curcumol group were higher than those in the low-dose curcumol group and antagonist group(P＜0.05).CONCLUSION Curcumol can help improve lung injury in SAP rats,and its regulatory mecha-nism may be related to activating the SIRT1/FOXO1 signaling pathway to induce the apoptosis of alveolar macrophages.
lung injurycurcumolmacrophagessilent information regulator transcript 1forkhead transcription factor 1
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