盐酸戊乙奎醚对胸部创伤-失血性休克复苏致大鼠急性肺损伤时NF-κB和AP-1活性的影响  

Effects of penehyclidine hydrochloride on activities of NF-κB and AP-1 during actue lung injury induced by blunt chest trauma-hemorrhagic shock and resuscitation in rats

作　　者：吴晓静[1] 冷燕[1] 高文蔚[2] 赵博[1] 薛锐[1] 詹丽英[1] 夏中元[1] 

机构地区：[1]武汉大学人民医院麻醉科,430060 [2]武汉大学人民医院重症医学科,430060

出　　处：《中华麻醉学杂志》2015年第6期751-754,共4页Chinese Journal of Anesthesiology

摘　　要：目的 探讨盐酸戊乙奎醚对胸部创伤-失血性休克复苏致大鼠急性肺损伤时NF-κB和激活蛋白-1（AP-1）活性的影响.方法 SPF级健康雄性SD大鼠30只,体重250～ 300 g,8周龄,采用随机数字表法,将其分为3组（n=10）：假手术组（S组）、胸部创伤-失血性休克复苏组（THSR组）和盐酸戊乙奎醚组（PHCD组）.胸部创伤-失血性休克复苏致急性肺损伤模型：将砝码（300 g）于95cm高处自由落体,撞击大鼠心前区,5 min后经股动脉放血,使MAP在15 min内降至35～45 mmHg,并维持60 min,然后进行复苏.PHCD组于失血性休克60 min时静脉注射盐酸戊乙奎醚2 mg/kg.于模型制备后6h,取血样,测定血清TNF-α浓度;随后取肺组织,测定肺含水量;采用比色法测定髓过氧化物酶（MPO）活;凝胶电泳迁移率变化分析法测定NF-κB和AP-1的活性;光镜下观察肺组织病理学结果;进行支气管肺泡灌洗,测定肺通透指数（LPI）.结果 与S组比较,THSR组和PHCD组肺含水量、LPI和血清TNF-α浓度、肺组织MPO、NF-κB和AP-1活性升高（P＜0.05）;与THSR组比较,PHCD组肺含水量、LPI和血清TNF-α浓度、肺组织MPO、NF-κB和AP-1活性降低（P＜0.05）.PHCD组肺组织病理学损伤较THSR组减轻.结论 盐酸戊乙奎醚可能通过抑制肺组织NF-κB和AP-1的活性,从而减轻胸部创伤-失血性休克复苏致大鼠急性肺损伤.Objective To investigate the effects of penehyclidine hydrochloride on activities of nuclear factor kappa B （NF-kB） and activator protein-1 （AP-1） during actue lung injury induced by blunt chest trauma-hemorrhagic shock and resuscitation （HSR） in rats.Methods Thirty male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly assigned into 3 equal groups （n =10 each） using a random number table：sham operation group （group S）,blunt chest trauma-HSR group （group THSR） and penehyclidine hydrochloride group （group PHCD）.The model of actue lung injury induced by blunt chest trauma-HSR was induced by dropping a 300 g weight onto a precordium in anesthetized rats.Blood was withdrawn via the femoral artery 5 min later until MAP was decreased to 35-45 mmHg within 15 min and maintained at this level for 60 min,followed by resuscitation.In PHCD group,PHCD 2 mg/kg was injected intravenously at 60 min after hemorrhagic shock.At 6 h after the model was established,blood samples were obtained for measurement of concentrations of tumor necrosis factor-alpha （TNF-α） in serum.The lungs were then removed for determination of lung water content,myeloperoxidase （MPO） activaty （by colorimetric assay）,NF-κB and AP-1 activaties （using electrophoretic mobility shift assay） in lung tissues,and for microscopic examination of pathologic changes （under light microscope）.The left lung was lavaged,and lung permeability index （LPI） was calculated.Results Compared with S group,lung water content,LPI,serum TNF-α level and activites of MPO,NF-κB and AP-1 were significantly increased in THSR and PHCD groups.Compared with THSR group,lung water content,LPI,serum TNF-α concentrations and activites of MPO,NF-κB and AP-1 were significantly decreased in PHCD group.The pathological damage to lung tissues was significantly reduced in PHCD group as compared with THSR group.Conclusion PHCD can inhibit activities of NF-κB and AP-1 in lung tissues,thus mitigating acute lung injury induced b

关 键 词：核因子ΚB 转录因子AP-1 胆碱能拮抗剂 胸部损伤 休克 出血性 呼 吸窘迫综合征 成人 

分 类 号：R614[医药卫生—麻醉学]