The Expression Analysis Of MiR-34a In Neonatal Rat Model Of Bronchopulmonary Dysplasia Induced By Hyperoxia

Objective Bronchopulmonary dysplasia?BPD?is commonly seen in small premature infants or very low birth weight infants.It is one of the chronic critical respiratory diseases that seriously affect the survival rate and quality of life of premature infants.In the past half a century,significant improvements have been made in the application of prenatal steroids and postpartum pulmonary surfactant?PS?,respiratory tract management and mechanical ventilation at home and abroad,so that the"new"BPD,which is mainly characterized by pulmonary development obstruction and pulmonary microcirculation disturbance,has gradually replaced"classic"BPD,as the main pathological feature of BPD.With the deepening of molecular genetics research,more and more scholars believe that BPD is caused by a variety of endogenous and exogenous stimuli?such as prenatal and postpartum infection and inflammation,ventilator volume injury and barotrauma,hyperoxia injury,patent ductus arteriosus,etc.?on the basis of genetic susceptibility,resulting in damage to immature lung tissue,and the uncontrolled development of pulmonary vessels and the abnormal repair of lung tissue after injury.As one of the powerful regulatory factors of gene expression,micro RNA?miRNA?is a kind of endogenous non-coding single-stranded small RNA,with a length of 19 to 25 nucleotides.Its main function is to regulate the target gene after transcription.Mi RNA is a large family,which widely exists in animals,plants and microorganisms,and participates in a variety of biological processes,so it has become a hot research direction.Mi R-34a is a member of the miR-34 family.Through in-depth study of miR-34a,it is found that miR-34a can regulate the occurrence of BPD through many ways,suggesting that miR-34a may be the potential action point of BPD.Therefore,this study intends to construct a"new"BPD model of neonatal SD rats induced by hyperoxia to further explore the relationship between miR-34a and BPD,so as to provide new ideas for the diagnosis and treatment of neonatal BPD.Methods Eighty new Sprague Dawley?SD?rats were randomly divided into hyperoxia group?Fi0₂=60%?and air group?Fi0₂=21%?within 2 hours after birth.The rats in the hyperoxia group were placed in a sealed oxygen box,and the oxygen concentration was maintained at 60%.The air group was placed in the same indoor atmospheric air,and the rest of the feeding conditions were the same.The lung tissue samples of SD rats were extracted on the 1st,7th,14th and 21st day after birth,and the pathological changes of lung tissue were observed by hematoxylin-eosin?HE?staining.The radiative alveolar count?RAC?and the mean alveolar diameter?MAD?and the thickness of alveolar septum?AST?were measured.Quantitative Real-time PCR technique was used to detect the expression of miR-34a in lung tissue of rats in hyperoxia group and air group at different time points.Results 1.Compared with the rats in the air group,the rats in the hyperoxia group gradually showed slow response,poor glossiness,head tremor,perioral cyanosis,increased breathing after oxygen and dyspnea.The body weight of rats in the hyperoxia group on the 7th,14th and 21st day after birth was significantly lower than that in the air group?P<0.05?.2.With the prolongation of oxygen exposure,the number of alveoli decreased,the volume increased,the structure simplified,the alveolar cavity enlarged obviously and the alveolar septum thickened in the hyperoxia group.3.With the increase of age,the RAC of rats in the air group and the hyperoxia group increased gradually,and the RAC in the hyperoxia group on the 7th,14th and 21st day after birth was significantly lower than that in the air group?P<0.05?.MAD and AST decreased gradually with the prolongation of oxygen exposure time in the air group,while MAD and AST increased gradually in the hyperoxia group.Compared with the air group,MAD and AST in the hyperoxia group increased significantly on the 7th,14th and 21st day after birth,and the difference was statistically significant?P<0.05?.4.With the prolongation of oxygen exposure time,the expression of miR-34a in the lung tissue of both the air group and the hyperoxia group increased at first and then decreased.The expression level of miR-34a in the hyperoxia group was significantly higher than that in the air group on the 7th,14th and 21st day after birth,and the difference was statistically significant?P<0.05?.Conclusion 1.The"new"BPD model of newborn SD rats can be successfully established by continuous exposure to 60%hyperoxia.2.The expression of miR-34a was up-regulated in the lung tissue of the"new"BPD model of neonatal rats.3.miR-34a may play an important role in the occurrence and development of BPD.