摘要
目的 评价脂氧素A4受体激动剂BML-111对大鼠失血性休克复苏诱发急性肺损伤的影响.方法 健康雄性SD大鼠32只,体重200 ～ 250 g,6～8周龄,采用随机数字表法,将其分为4组（n=8）：假手术组（S组）、失血性休克复苏组（HSR组）、BML-111组和BML-111＋脂氧素A4受体拮抗剂BOC-2组（BOC-2组）.通过放血制备失血性休克模型,休克维持30 min,然后回输放出的血液及2倍放血量的乳酸钠林格氏液进行复苏.BOC-2组在放血前腹腔注射BOC-2（50 μg/kg）,BML-111组和BOC-2组在复苏开始时腹腔注射BML-111（1 mg/kg）.复苏结束后2h处死大鼠,收集支气管肺泡灌洗液（BALF）,进行中性粒细胞计数.取肺组织,用于观察肺组织病理学结果,测定湿/干重比值（W/D比值）、IL-1β和IL-6含量、丝裂原活化蛋白激酶（MAPK）磷酸化水平.结果 与S组比较,HSR组BALF中性粒细胞计数、肺组织W/D比值、IL-1β和IL-6、MAPK磷酸化水平升高（P＜0.05）；与HSR组比较,BML-111组BALF中性粒细胞计数、肺组织W/D比值、IL-1β、IL-6和MAPK磷酸化水平降低（P＜0.05）；与BML-111组比较,BOC-2组BALF中性粒细胞计数、肺组织W/D比值、IL-1β、IL-6和MAPK磷酸化水平升高（P＜0.05）.结论 BML-111可减轻大鼠失血性休克复苏诱发急性肺损伤,其机制与抑制MAPK通路激活从而减轻肺组织炎性反应有关.
Objective To evaluate the effect of lipoxin A4 receptor agonist BML-111 on acute lung injury induced by hemorrhagic shock and resuscitation in rats.Methods Thirty-two healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 200-250 g,were randomized into 4 groups （n =8 each） using a random number table：sham operation group （S group）,hemorrhagic shock/resuscitation group （HSR group）,BML-111 group,and BML-111 plus BOC-2 （lipoxin A4 receptor antagonist） group （BOC-2 group）.The animals were anesthetized with 2% pentobarbital sodium 80 mg/kg,tracheostomized and mechanically ventilated.Left common carotid artery was cannulated for blood-letting and fluid infusion.Hemorrhagic shock was induced according to the method described by Kochanek et al.MAP was reduced to 35-45 mmHg and maintained at this level for 30 min.The animals were then resuscitated for 30 min with infusion of the blood withdrawn and lactated Ringer＆#39; s solution 2 times the volume of blood withdrawn.In BML-111 and BOC-2 groups,BML-111 （1 mg/kg） was injected intraperitoneally at the beginning of resuscitation.In BOC-2 group,BOC-2 （50 μg/kg） was injected intraperitoneally before blood-letting.The rats were sacrificed at 2 h after completion of resuscitation.Bronchoalveolar lavage fluid （BALF） was collected for determination of neutrophil count.Lungs were excised for microscopic examination of the pathological changes and for determination of wet/dry lung weight ratio （W/D ratio）,contents of interleukin-1 （IL-1β） and IL-6,and phosphorylation of mitogen-activated protein kinase （MAPK）.Results Compared with group S,the neutrophil count in BALF,W/D ratio,contents of IL-1β and IL-6,and phosphorylation of MAPK were significantly increased in HSR group （P 〈 0.05）.The neutrophil count in BALF,W/D ratio,contents of IL-1β and IL-6,and phosphorylation of MAPK were significantly lower in BML-111 group than in HSR group,and higher in BOC-2 group than in BML-111 group （P 〈 0.05）.Conclusion BML-111 can att
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2014年第1期90-93,共4页
Chinese Journal of Anesthesiology
基金
国家自然基金重点项目（30930089）
卫生部临床重点学科项目（2010-47）
关键词
受体
脂氧素
休克
失血性
呼吸窘迫综合征
成人
Receptors,lipoxin
Shock,hemorrhagic
Respiratory distress syndrome,adult
