右美托咪定联合乌司他丁对内毒素血症大鼠肺组织炎性反应的影响  

Effects of dexmedetomidine-ulinastatin combination on inflammatory responses in lung tissues of endotoxic rats

作　　者：姜远旭[1,2] 徐世元[1] 陶明哲 张雪萍 赵伟[1] 周树勤[1] 

机构地区：[1] 南方医科大学附属珠江医院麻醉科, 广东 广州510280 [2] 深圳市人民医院麻醉科

出　　处：《中国急救医学》2014年第4期367-371,386,共6页Chinese Journal of Critical Care Medicine

摘　　要：目的：研究右美托咪定（Dexmedetomidine， DEX）联合乌司他丁（ulinastatin， UTI）对内毒素血症（ endotoxemia ）大鼠肺组织炎性反应的影响。方法健康雄性Wistar大鼠40只，随机分为五组：生理盐水对照组（ NS组）、LPS模型组（ L组）、右美托咪定治疗组（ L＋D组）、乌司他丁治疗组（ L＋U组）、右美托咪定＋乌司他丁治疗组（ L＋D＋U组）。 NS组股静脉给予5 mL/kg生理盐水；L组股静脉给予脂多糖（ LPS）10 mg/kg；L＋D组股静脉给予LPS 10 mg/kg，即刻持续输注右美托咪定1μg/（kg＆#183; h）；L＋U组股静脉给予LPS 10 mg/kg，即刻腹腔注射乌司他丁20000 U/kg；L＋D＋U组股静脉给予LPS后即刻股静脉持续输注右美托咪定1μg/（ kg＆#183; h）及腹腔注射乌司他丁20000 U/kg。分别在注射LPS或NS后6 h处死动物。检测肺组织肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、髓过氧化物酶（MPO）活性及细胞间黏附分子1（ICAM-1）、核因子-κB（NF-κB）的表达情况。 HE染色光镜下观察肺组织病理学变化。结果与NS组比较，L组肺组织TNF-α浓度、IL-1β浓度、IL-6浓度、MPO活性及ICAM-1、NF-κB表达明显升高。与L组比较，L＋D＋U组TNF-α浓度、IL-1β浓度、IL-6浓度、MPO活性及ICAM-1、NF-κB表达降低，而右美托咪定和乌司他丁单独治疗组没有明显变化。结论右美托咪定联合乌司他丁治疗通过抑制NF-κB的活性减轻内毒素血症大鼠肺组织炎性反应。Objective To investigate the effects of dexmedetomidine -ulinastatin combination on inflammatory responses in lung tissues of endotoxic rats .Methods Male Wistar rats were randomly divided into five groups： saline control group （ NS group ） was given saline （ 5 mL/kg, iv ） alone;endotoximea group （L group） was given LPS （10 mg/kg, over 10 mins）;dexmedetomidine-endotoxin group （ L＋D group） was treated identically to the endotoxemic group with the additional administration of dexmedetomidine [ infusion at 1μg/（ kg＆#183; h） ] immediately after LPS injection;ulinastatin-endotoxin group （ L＋U group） was treated identically to the endotoxemic group with the additional administration of ulinastatin （20 000 U/kg, ip） immediately after LPS injection; dexmedetomidine ＋ulinastatin -endotoxin group （ L ＋D ＋U group ） received dexmedetomidine [ infusion at 1 μg/（ kg＆#183; h ） ] and ulinastatin （20 000 U/kg, ip） immediately after LPS injection .Six hours after LPS or saline injection , rats were sacrificed and the lungs were removed for evaluation of histological characteristics and determination of the cytokine （ TNF-α, IL-1β, IL -6 ） concentrations , myeloperoxidase （ MPO ）＆amp;nbsp;activity.The pulmonary expression of intercellular adhesion molecule -1 （ ICAM -1 ） and nuclear factor-κappa B （ NF-κB） p65 was evaluated by immunohistochemistry and Western blotting .Results LPS induced marked lung histological injury and a significant increase in the cytokine （ TNF -α, IL-1β, IL-6） concentrations, myeloperoxidase （MPO） activity in the lung.All these effects were attenuated by dexmedetomidine -ulinastatin combination but not by dexmedetomidine or ulinastatin alone.The expression of ICAM -1 and NF -κB p65 was increased in the L group , and this enhancement of ICAM-1 and NF-κB p65 expression was much less in the L ＋D＋U group but not by L＋D or L ＋U alone.Conclusion Dexmedetomidine -ulinastatin combination inhibits inflammatory rea

关 键 词：右美托咪定 乌司他丁 内毒素血症 中性粒细胞 细胞因子 核因子-κB( NF-κB) 

分 类 号：R135.2[医药卫生—劳动卫生]