SIRT1 Signaling Pathway Mediated Caffeine In Preventing Bronchopulmonary Dysplasia In Preterm Infants

Objective:To explore whether SIRT1 signaling pathway mediating the effect of caffeine on preventing premature bronchialpulmonary hypoplasia by detecting SIRT1 location and testing the protein level of SENP1,SIRT1 in nucleus,SIRT1 in cytoplasm,acetylation P53 in PBMCs in each group,and comparing the incidence of BPD.Methods:Sixty-Five premature infants were admitted to the neonatology department of the affiliated hospital of Southwest medical university during August 2015 to June 2016 who gestational age was less than 32 weeks,the weight was less than 1500g,the admission time was within 24 hours,diagnosed with NRDS,and the time of hospital stay was more than 28 days,but the baby who had less than 28 days in hospital,congenital diseases and other congenital malformations were not included.According to the needed oxygen concentration and whether their parents agreed to use the caffeine,they were devited into four groups,Control group[n=22,gastational age（30.28±0.94）weeks,birth weight（1228±110）g]:FiO₂=21%or FiO₂>21%but total oxygen time less than 24 hours and not used caffeine,Control and caffeine group[n=25,gastational age（30.18±1.38）weeks,birth weight（1230±87）g]:FiO₂=21%or FiO₂>21%but total oxygen time less than 24 hours and used caffeine,Hyperoxia groups[n=6,gastational age（29.5±1.11）weeks,birth weight（1138±114）g]:FiO₂>40%and total oxygen time is more than 24 hours and not use caffeine,Hyperoxia groups and caffeine[n=12,gastational age（29.26±1.88）weeks,birth weight（1242±24）g]:FiO₂>40%and total oxygen time is more than 24 hours and use caffeine.There was no significant difference in gestational age,birth weight,PS utilization rate,ventilator utilization rate and ventilator usage time in four groups（P>0.05）,and the glucocorticoid usage and use of time to compare in hyperoxia group and hyperoxia plus caffeine group,the difference was not statistically significant（P>0.05）.SIRT1 location was detected by immunofluore-scence,the protein content of SENP1,SIRT1 in nucleus,SIRT1 in cytoplasm,AC-P53 in PBMC were detected by Western blot,and compared the ratio of SIRT1 in the nucleus to SIRT1 in cytoplasm and the incidence of BPD.Results:1 Compared with hyperoxia group,the translocation rates of SIRT1 decreased in 14^th day and 28^th day（the translocation rates of SIRT1 were10.07%±0.74%and 8.89%±0.32%）,P<0.05,the difference was statistically significant.2 Compared with the control group,in hyperoxia group,the expression of SENP1,SIRT1 in cytoplasm,acetylation P53 gradually increased at each point in time,P<0.05,the difference was statistically significant;but SIRT1 in the nucleus and the ratio of SIRT1 in the nucleus to SIRT1 in cytoplasm were gradually decreased at each point in time,P<0.05,the difference was statistically significant.Compared with hyperoxia group,in hyperoxia and caffeine group,SENP1,SIRT1 in cytoplasm,acetylation P53appeared to reduce in 14^th day and 28^th day,SIRT1 in nucleus and the rate of SIRT1 in the nucleus to SIRT1 in cytoplasm were increased in 14^th day and 28^thh day,P<0.05,the difference was statistically significant.3 The total incidence of BPD was 10.7%,and in the control group and the control plus caffeine group had no BPD happened,the incidence of BPD in hyperoxia group was 83%,the incidence of BPD in hyperoxia and caffeine group was 25%,χ²=4.938,P<0.05,the difference was statistically significant.Conclusion Caffeine can reduce the incidence rate of bronchialpulmonary dysplasia under the condition of hyperoxia exposure,the SIRT1 signaling pathway was involved,The mechanism might be that caffeine reduced the expression of SENP1,inhibited SIRT1 nucleoplasm,reduced the expression of acetylation P53.