Intervention Effect Of Dexamethasone For Bronchopulmonary Dysplasia And The Expression Of NF-κBp65and TNF-a In Neonatal Rats Caused By Intrauterine Infection

Objectives：Now more and more people think intrauterine infection is close to the neonatalof bronchial lung hypoplasia[1].This study through injecting the lipopolysaccharide(LPS) into the pregnant rat abdominal cavity to make the model of intrauterineinfection, To study the expression of the NF-κ Bp65,TNF-α,in newborn rats’lungtissue which have bronchopulmonary dysplasia caused by intrauterine infection, Toevaluate the intervention effect of dexamethasone on bronchopulmonary dysplasia inneonatal rats caused by intrauterine infection.Methods:1. Experimental groups:30pregnant17d rats were randomly divided intonormal saline control group (group NS), lipopolysaccharide group (group LPS) anddexamethasone intervention group (group DEX), each group had10pregnant rats.LPS group of pregnant rats are injected of LPS in350μ g/kg through abdominalcavity on the Seventeenth, Eighteenth day for2consecutive days, DEX group ofpregnant rats are injected of LPS in350μ g/kg through abdominal cavity on theSeventeenth,18days for2consecutive days,0.5mg/kg of dexamethasone is injectedto abdominal cavity after injecting of lip polysaccharide1h.NS group of pregnant ratsare injected of the same volume of normal saline at the same time point.2. Sample collection: Random out of2pregnant rats from three groups aftermodeling, removed their placenta, uterine fixed in4%neutral formalin for HEstaining after executed. The neonatal rats natural birth were weighted afterdecapitation according to p1，p3，p7and p14four time points, rapid thoracotomy inlung tissue and taken out, washed with physiological saline, weighted it after surfacewater of lung tissue was dried by paper, then fixed lung tissue placed in4%neutralformalin for HE and immunohistochemical staining.3. Experimental method: observed pathological changes in uterus, placenta ofpregnant rats of each group by HE staining; detected three groups of neonatal rats’ body weight, lung weight. Lung index (lung weight/body weight); Staining the Lungtissue with HE; Counting the radial alveolar count (RAC) of the1d,3d,7d after thenewborn rats birth under microscope; Detected the expression of nuclear factor-κBp65(NF-κ Bp65) and tumor necrosis factor alpha (TNF-α) in lung tissue after thenewborn rats birth of the1d,3d,7d by Immunohistochemistry.Result：1.30pregnant rats were normal eat and activities, no deaths occurred in them,Pregnant rats delivery, group NS received70(70/72) rats; group LPS received70(62/69) rats; group DEX received63(63/67) rats; After Intrauterine infection：thematernal Placental and uterine pathology shows signs of vascular congestion, edema,neutrophil infiltration. The control group of placental and uterine detection showed noobvious inflammatory reaction.2.The pathological changes of lung tissue: After Intrauterine infection：Thepathology of the neonatal lung characterized by fewer alveoli，less septa at p3, feweralveoli and thicken septa at p14.，The pathology of the neonatal lung of DEX groupwas similar to LPS group, but the degree of ease. The radial alveolar count of LPSgroup was decreased than the control group at p3，p7and p14(P<0.05), Afterintervention of dexamethasone: The radial alveolar count of was increased than theLPS group at p3，p7and p14(P<0.05).Three groups of neonatal rats lung tissueshowed no obvious pulmonary fibrosis.3.After Intrauterine infection： the body weight and the lung weight wasincreased at p1，p3，p7and p14(P<0.05). The body weight and the lung weight ofDEX group was increased at p1，p3，p7and p14(P<0.05) compared with LPS group.4. The expression of NF-κ Bp65and TNF-α of LPS group in lung tissue inneonatal rats was increased at p1，p3，p7and p14(P<0.01) compared with the controlgroup. There was a positive correlation between the expression of NF-κ Bp65andTNF-α（r=0.975， P<0.01）.5. DEX group compared with LPS group: The expression of NF-κ Bp65andTNF-α of in lung tissue in neonatal rats was decreased at p1，p3，p7and p14(P<0.01).There was a positive correlation between both decreased（r=0.967，P<0.01）. Conclusion:1. Intraperitoneal injection of LPS resulted in maternal uterine and placentalvascular congestion, edema, infiltration of neutrophils, to establish the model ofintrauterine infection of pregnant mice. After Intrauterine infection： the bodyweight,the lung weight and Lung index was decreased，The pathology of the neonatallung characterized by fewer alveoli，less septa and thicken septa，The radial alveolarcount was decreased which is similar to the BPD，which indicates that the intrauterineinfection t impaired alveolar development, was one of the important reasons forBPD.2. After Intrauterine infection：the expression of NF-κ Bp65and TNF-α in lungtissue in neonatal rats was increased after birth，Prompt cytokine response plays animportant role in the neonatal rat bronchial pulmonary dysplasia by intrauterineinfection.3. After Intrauterine infection and intervention of dexamethasone: the expressionof NF-κ Bp65and TNF-α in lung tissue in neonatal rats had a consisted trend. therewas a positive correlation between them, Prompt There was a synergistic effectbetween NF-κ Bp65and TNF-α in neonatal rats of bronchopulmonary dysplasiainduced by intrauterine infection.4. After used dexamethasone in intrauterine infection early: the expression ofNF-κ Bp65and TNF-α in lung tissue in neonatal rats was decreased, the pathologyof the neonatal lung was abated, the radial alveolar count was decreased and the bodyweight and the lung weight were increased. Dexamethasone plays a protective role inneonatal rats of bronchopulmonary dysplasia induced by intrauterine infection.