CAJ | 학술논문

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· 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· 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。
목적：연구우미탁미정（Dexmedetomidine， DEX）연합오사타정（ulinastatin， UTI）대내독소혈증（ endotoxemia ）대서폐조직염성반응적영향。방법건강웅성Wistar대서40지，수궤분위오조：생리염수대조조（ NS조）、LPS모형조（ L조）、우미탁미정치료조（ L＋D조）、오사타정치료조（ L＋U조）、우미탁미정＋오사타정치료조（ L＋D＋U조）。 NS조고정맥급여5 mL/kg생리염수；L조고정맥급여지다당（ LPS）10 mg/kg；L＋D조고정맥급여LPS 10 mg/kg，즉각지속수주우미탁미정1μg/（kg· h）；L＋U조고정맥급여LPS 10 mg/kg，즉각복강주사오사타정20000 U/kg；L＋D＋U조고정맥급여LPS후즉각고정맥지속수주우미탁미정1μg/（ kg· h）급복강주사오사타정20000 U/kg。분별재주사LPS혹NS후6 h처사동물。검측폐조직종류배사인자-α（TNF-α）、백세포개소-1β（IL-1β）、백세포개소-6（IL-6）、수과양화물매（MPO）활성급세포간점부분자1（ICAM-1）、핵인자-κB（NF-κB）적표체정황。 HE염색광경하관찰폐조직병이학변화。결과여NS조비교，L조폐조직TNF-α농도、IL-1β농도、IL-6농도、MPO활성급ICAM-1、NF-κB표체명현승고。여L조비교，L＋D＋U조TNF-α농도、IL-1β농도、IL-6농도、MPO활성급ICAM-1、NF-κB표체강저，이우미탁미정화오사타정단독치료조몰유명현변화。결론우미탁미정연합오사타정치료통과억제NF-κB적활성감경내독소혈증대서폐조직염성반응。
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· 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· 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 ) 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 reaction in the lung tissues of endotoxic rats by suppressing NF -κB activation.