Ultrasound Guided Intra-amniotic Instillation Of Pulmonary Surfactant Combined With Ambroxol For The Prevention Of Lung Injury In Preterm Rabbits

Background: Preterm infants,whose lungs are immature and lack of pulmonary surfactant(PS),often lead to lung injury,which is the biggest challenge after birth.Ensuring pulmonary ventilation is a prerequisite for survival in preterm infants.Exogenous PS replacement therapy and prenatal maternal medication to promote fetal lung maturity are currently the most common methods for the prevention of lung injury.However,intracheal administration of PS and prenatal glucocorticoids have some side effects,making their safeties controversial.Ultrasound guided intra-amniotic instillation of PS and prenatal ambroxol hydrochloride(AH)for the prevention of lung injury in preterm infants have been reported in recent years,but the effectiveness of the two methods remains an area of concern and needs more researches.What’s more,whether the combination of them can better prevent lung injury has yet to be studied.Objective: To investigate the effects of ultrasound guided intra-amniotic instillation of pulmonary surfactant,prenatal ambroxol hydrochloride and combined use of the two methods for the prevention of lung injury in preterm rabbits.Methods: Twenty pregnant New Zealand rabbits were randomly divided into four groups as follows: ultrasound guided intra-amniotic instillation of pulmonary surfactant before cesarean section(PS group),prenatal ambroxol hydrochloride(AH group),ultrasound guided intra-amniotic instillation of pulmonary surfactant before cesarean section combined with prenatal ambroxol hydrochloride(PS+AH group)and Control group.On the 27 th day of pregnancy,fetuses were removed by cesarean section.The birth weight and the survival time of the preterm rabbits were recorded.Lung tissue sections were taken for HE staining to observe the degree of lung injury and pathological score.The bronchoalveolar lavage fluid was collected to detecte the concentration of IL-6 and dipalmitoyl phosphatidylcholine(DPPC)by ELISA or HPLC.And the expression level of pulmonary surfactant-associated protein A(SP-A)in lung tissue was detected by immunohistochemistry.Results:1.Prenatal administration of PS or AH had no significant effect on the birth weight of preterm rabbits(P>0.05),but significantly prolonged the survival time(P<0.05).2.Pathological changes of lung injury were observed in preterm rabbits of Control group.The pathological score of lung injury in PS+AH group was the lowest among the four groups(P<0.05).3.The concentration of IL-6 in Control group was significantly increased,while the concentration of IL-6 in PS+AH group was the lowest(P<0.05).4.Compared with the Control group,the DPPC content in the bronchoalveolar lavage fluid of PS group,AH group and PS + AH group was significantly increased.Among them,the DPPC content of PS +AH group increased most significantly(P<0.05).5.Prenatal administration of PS or AH increased the expression of SP-A in lung tissue,especially in PS+AH group(P<0.05).Conclusions:1.Ultrasound guided intra-amniotic instillation of pulmonary surfactant and prenatal administration of ambroxol hydrochloride can effectively reduce the expression of inflammatory cytokines IL-6,upregulate the content of DPPC and SP-A,so as to prolong the survival time of preterm rabbits,improve lung morphological features and therefore play a role in the prevention of lung injury in preterm rabbits.2.Combination of ultrasound guided intra-amniotic instillation of pulmonary surfactant and prenatal administration of ambroxol hydrochloride for the prevention of lung injury in preterm rabbits is more useful than using either method alone.