| Background Bronchopulmonary dysplasia(BPD)is a prevalent clinical complication of preterm birth.Classical BPD is characterized by pulmonary fibrosis,while new BPD is characterized by simplified alveolar structure and pulmonary vascular remodeling.At present,the pathogenesis of BPD is still unclear.Existing studies have confirmed that oxidative stress plays an important role in the occurrence and development of BPD.It is not clear whether nuclear factor-erythroid 2-related factor 2(Nrf2),as a key factor of oxidative stress,is the main factor in its regulation.In clinical practice,caffeine has the distinction of reducing the incidence of BPD in premature infants with apnea.The lung protective effect of caffeine on BPD has been confirmed by a number of clinical studies,but the specific mechanism and molecular pathways related to anti-oxidative stress activity remain to be clarified.Therefore,exploring the protective effect of caffeine on lung injury in hyperoxia induced BPD through caffeine intervention and revealing the mechanism of caffeine regulating oxidative stress are expected to promote the planning of more targeted prevention and treatment strategies for BPD and improve long-term outcomes.Objectives To investigate the protective effect of caffeine on oxidative stress injury induced by hyperoxia in neonatal Sprague-Dawley(SD)rats with BPD and its related mechanism.Methods Neonatal rats were randomly distributed to model group(H group),caffeine intervention group(HC group),air control group(N group)and intervention control group(NC group),with 24 rats in each group.The high oxygen induction method was used to establish the BPD model.Six samples of blood and lung tissue were collected from each group on day 3,7,14 and 21.Each group on day 21 of four groups measured their weight continuously.The upper lobe of the right lung from each infant rat was employed to measure Wet/Dry(W/D)weight ratio in each group;the lower lobe of the right lung was sliced after paraffin embedding and stained with hematoxylin-eosin(HE)to observe morphological changes and calculate radial alveolar count(RAC)values;the levels of malondialdehyde(MDA)and superoxide dismutase(SOD)were determined to evaluate the oxidative stress level of newborn BPD rats;Real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-q PCR)was employed to measure the relative expression level of Nrf2 m RNA.Results(1)H group showed a gradual decline in activity after 3 days and an increasing trend in body weight after 14 days.(2)W/D value of H group reached its peak at day 14,and the trend of HC group was similar to that of H group.(3)The lung tissue structure of H group was irregular,RAC value of which decreased apparently after 7 days of peak,and meanwhile statistically the difference between H group and HC group was significant(P < 0.01).(4)The MDA value of H group gradually decreased on day 14 and increased on day 7,while the SOD activity decreased obviously on day 7,and the difference between H group and HC group was statistically significant at 14 days and 21 days(P<0.05).(5)The expression of Nrf2 m RNA in H group was significantly enhanced at day 7and stabilized at day 14,and there were statistically significant differences between H and HC groups at day 3,day 7 and day 14,while there were no evidently significant differences at day 21.(6)The relative expression level of Nrf2 m RNA was correlated with MDA positively(P<0.01)and correlated with SOD negatively(P<0.01)in H and HC groups.Conclusions Caffeine plays an antioxidant protective role in oxidative stress of bronchopulmonary dysplasia in lung tissue.Caffeine can regulate oxidative stress response through the Nrf2 pathway and alleviate oxidative stress injury in the lung of BPD induced by hyperoxia. |
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