Study On The Relationship Between NF-κB-Regulated HO-1 And The Oxidative Stress Factors And The Development Of Meconium Aspiration Syndrome

【Background and Purpose】Meconium aspiration syndrome(MAS)is one of the major clinical problems faced in the neonatal period,an inflammatory neonatal lung disease that can lead to severe respiratory failure with potentially fatal consequences in term and overdue infants,and the pathogenesis of MAS is not well understood due to the complex composition of meconium.In this study,we investigated the link between the regulatory NF-κB pathway and HO-1 and related oxidative stress factors Drp-1 and PGC-1α to explore the pathogenesis of meconium aspiration pneumonia and provide a reference and theoretical basis for its diagnosis and treatment.【Methods】Part Ⅰ: Sixty SD neonatal rats,male and female,were divided into saline group,meconium aspiration syndrome model group,NF-κB inhibitor SN50 low,medium and high concentration group,10 rats in each group,and the rest were reserved.The neonatal rat meconium aspiration pneumonia model was prepared by tracheal exposure with 2 ml/kg of saline in the trachea as the control group,and 2 ml/kg of meconium suspension in the trachea of the remaining groups.Part Ⅱ: At 24 h after successful modeling,the saline group and the model group were not treated with NF-κB inhibitors,and the NF-κB inhibitor SN50 low,medium and high concentration groups were injected intraperitoneally with 100 ul each of 10 μg/ml,30 μg/ml and 60 μg/ml concentrations of SN50.6 h later,all groups were executed and removed.Part Ⅲ:(1)Immunohistochemistry to detect the expression of p65,HO-1,PGC-1α,Drp-1 in lung tissues before and after treatment with NF-κB inhibitor in five groups;(2)Western Blot immunoblot to detect the expression of p65,HO-1,PGC-1α,Drp-1 protein in lung tissues before and after treatment with NF-κB inhibitor in five groups.【Results】1.Intratracheal tube injection of 2 ml/kg of meconium suspension in neonatal rats caused the corresponding lung injury.2.There was a trend of increasing protein expression levels of p65 and Drp-1 and decreasing protein expression levels of HO-1 and PGC-1α in the lung tissue of the animals in the fetal fecal aspiration syndrome model group compared with the saline control group.3.After intraperitoneal injection of different concentrations of SN50 in neonatal rats with meconium aspiration syndrome,the protein expression levels of p65 and Drp-1in neonatal rat lung tissue were significantly down-regulated,and the protein expression levels of HO-1 and PGC-1α were gradually up-regulated in a concentration-dependent manner with SN50.【Conclusion】1.A model of meconium aspiration pneumonia in neonatal rats was successfully prepared by tracheal exposure and intratracheal injection of 2 ml/kg of meconium suspension,which provides a good basis for the study of meconium aspiration pneumonia and related basic research.2.Meconium inhalation can activate NF-κB pathway,activate and up-regulate nuclear stain p65 and Drp-1 expression,and down-regulate HO-1 and PGC-1α protein expression level.3.With the increase of SN50 concentration,the expression of p65 and Drp-1 in the lung tissue of neonatal rats with meconium aspiration syndrome was down-regulated,and its protein decreased most obviously at the SN50 of 60 μg/ml,while the proteins of HO-1 and PGC-1α were gradually up-regulated in dependence on the SN50 concentration.4.In this study,the changes in the expression levels of HO-1,Drp-1,and PGC-1αwere clarified by injecting SN50 into neonatal rats with SD meconium aspiration syndrome model to inhibit the lung inflammation caused by NF-κB pathway,which provides a reference for clarifying the mechanism of pneumonia in neonatal meconium aspiration syndrome,thus opening up a new way to study the treatment of neonatal meconium aspiration syndrome;it is intended for early intervention of It is proposed to provide a basis for early intervention of neonatal meconium aspiration pneumonia and treatment of lung tissue inflammation.