Protective effect of dexmedetomidine combined with artesunate modulation of PERK/ATF4/CHOP signaling pathway in ischemia-reperfusion lung injury rats
Objective:To explore the protective effect of dexmedetomidine(Dex)combined with artesunate(ART)on ischemia-reperfusion lung injury in rats and its regulatory mechanism.Methods:A total of sixty SD rats were randomly divided into Sham operation group,model control group,ART(100 mg/kg),Dex(30 μg/kg),combination(30 μg/kg Dex+100 mg/kg ART),and nimodipine groups(200 mg/kg),with 10 rats in each group.Except for the Sham group,the rats in the remaining five groups were established in the ischemia-reperfusion lung injury model.The Sham group only opened the chest without ligation.After the experiment,the arterial blood was taken to detect the arterial blood gas indicators:Carbon dioxide partial pressure(PaCO2)and oxygen partial pressure(PaO2);The kits were used to detect the redox indicators malondialdehyde(MDA),superoxide dismutase(SOD)and myeloperoxidase(MPO)in lung tissue,and the levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-18 in serum and lung tissue;Hematoxylin-eosin staining was used to detect the pathological changes of lung tissue;TUNEL staining was used to detect cell apopto-sis;Western Blot method was used to detect the expression of PERK/ATF4/CHOP pathway-related proteins in lung tissue.Results:Compared with those in the Sham group,PaCO2 and MDA content,MPO activity,the contents of TNF-α,IL-1β,and IL-18,and the expression of PERK,ATF4,CHOP protein were significantly increased,the PaO2,serum SOD activity were reduced in the model control group(P<0.05).Compared with those in the model group,the apoptosis rate,PaCO2 and MDA content,MPO activity,the contents of TNF-α,IL-1β,IL-18,and the expression of PERK,ATF4,CHOP proteins were reduced in the ART group,Dex group,combination group and ni-modipine group,the PaO2 and SOD activity were increased,and the changes of above indexes in the combination group were better than those in the monotherapy group(P<0.05).Conclusion:Dex combined with ART can protect rat ischemia-reperfusion lung injury,possibly by inhibiting the PERK/ATF4/CHOP signaling pathway.
万方数据
维普
