Protective Effect And Mechanism Of Interleukin 22 Against Hyperoxia-induced Lung Injury In Neonatal Rats

Objective:Establish hyperoxia-induced lung injury model in neonatal SD rats,to observe the effect of high concentration oxygen on body weight,lung pathology and cytokine levels in neonatal SD rats,and through the detection of signal transducer and activator of transcription 3(STAT3)signaling pathway protein and gene level changes to discuss the protective effect and mechanism of interleukin 22 against hyperoxia-induced lung injury in neonatal rats.Methods:The neonatal SD rats in 12 hours were randomized to control group,hyperoxia group and treatment(IL-22)group.Each group was randomly divided into three subgroups of 1,3,7 days(n=9).Body mass and survival rate in every group were detected,lung pathological was observed by HE staining,and IL-1β in BALF and in plasma was detected by ELISA.The protein concentration in BALF were determinated by BCA,Western bloting was used to detect the protein levels changes of STAT3,phosphorylated signal transducer and activator of transcription 3(pSTAT3),B cell lymphoma/leukemia-2(Bcl-2)and Bcl-2 associated X protein in lung tissues;The mRNA levels of Bcl-2,Bax,IL-1β tumor necrosis factor alpha(TNF-a)and cytokine signaling suppressor 3(SOCS3)in lung tissue were detected by Real-Time PCR.Results:Hyperoxia exposure for 7 d,compared with the control group,the survival rate of the hyperoxia group was significantly lower than that of the control group,the survival rate of the treatment group was significantly higher than that of the hyperoxia group.After exposure to hyperoxia for 1 day,the body mass in three groups showed no significant difference,and the lung tissue structure was complete.Exposure to hyperoxia for 3 or 7 days,the body mass in hyperoxia was significant lower than control group and treatment group,and IL-1β in BALF and in plasma was significantly enhanced,the lung tissue structure was destroyed,which aggravated with the time of hyperoxia.Compared with the control group,the mRNA levels of Bax,IL-1β,TNF-α,SOCS3 were increased,the mRNA level of Bcl-2 was significantly decreased.After treatment with IL-22,the mRNA levels of Bcl-2,SOCS3 were significantly increased in lung tissue,and the mRNA levels of Bax,IL-1β,TNF-a were reduced.Compared with the control group,the protein levels of pSTAT3,SOCS3,Bax were increased in the hyperoxia group lung tissue,and Bcl-2 protein decreased;The levels of pSTAT3,SOCS3,Bcl-2 protein were obviously increased,and the Bax decreased in treatment group compared with the hyperoxia group.Conclusions:High concentration of oxy can cause neonatal SD rats lung tissue pathological damage,inflammatory factors and apoptosis level increased.IL-22 can activate the STAT3 signaling pathway to reduce the hyperoxia-induced lung injury and lung protein leakage,inflammatory factors and apoposis factor expression,confirmed that IL-22 can activate STAT3 signal pathway and plays a protective role in hyperoxia-induced lung injury.