Effect of BML-111 on NF-κB pathway during acute lung injury induced by hemorrhagic shock and resuscitation in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of BML-111 on NF-κB pathway during acute lung injury induced by hemorrhagic shock and resuscitation in rats.Methods Thirty-two adult male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 4 groups (n =8 each) using a random number tablesham operation group (group S),hemorrhagic shock and resuscitation group (group HSR),BML-111 group,and BML-111 + BOC-2 (lipoxin A4 receptor antagonist) group (group BOC-2).The animals were anesthetized with intraperitoneal pentobarbital sodium.Hemorrhagic shock was induced by blood letting and maintained for 30 min.The animals were then resuscitated for 30 min by infusion of the shed blood and lactated Ringer's solution.In group BOC-2,BOC-2 (50 μg/kg) was injected intraperitoneally before blood letting.In BML-111 and BOC-2 groups,BML-111 (1 mg/kg) was injected intraperitoneally at the beginning of resuscitation.The rats were sacrificed at 2 h after the end of resuscitation and lungs were removed for determination of pathological changes,myeloperoxidase (MPO) activity,intercellular adhesion molecule-1 (ICAM-1) expression (by immunohistochemistry),tumor necrosis factor-alpha (TNF-α) content (by ELISA),and NF-κB p65 and IκB-α expression (by Western blot).Results Compared with group S,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and IκB-α expression was down-regulated in group HSR.Compared with group.HSR,the MPO activity,ICAM-1 expression,and TNF-α content were significantly decreased,NF-κB p65 expression was down-regulated,IκB-α expression was up-regulated,and pathological changes of lung were attenuated in group BML-111.Compared with group BML-111,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and lκB-α expression was down-regulated,and pathological changes of lung were aggravated in group BOC-2.Conclusion BML-1 11 inhibits activation of NF-κB pathway and inflammatory responses,thus mitigating acute lung injury induced by hemorrhagic shock and resuscitation in rats.