【摘要】 目的观察NF-κB活化阻断剂是否对盲肠结扎穿刺所致豚鼠急性肺损伤具有防治作用,探讨NF-κB活化阻断剂防治肠源性肺损伤的机制。方法用盲肠结扎穿刺(CLP)法建立豚鼠急性肺损伤模型,同时经口给予布洛芬167 mg/kg和肌内注射维生素E 174 mg/kg预防和治疗,结合动脉血气分析、外周血白细胞计数、肺湿重/干重比值(W/D)及肺组织病理变化,免疫组化方法研究肺组织NF-κB的活化。结果CLP组动物在6 h后开始缓慢出现症状,呼吸急促100~110次/min(正常呼吸80~95次/min),蜷缩,对外界刺激敏感;16 h有少量泡沫状分泌物由鼻腔溢出,呼吸变得窘迫,倦怠,卧伏,不喜活动;24 h呼吸窘迫十分显著,泡沫状分泌物(带血性)由鼻腔溢出明显增多,呼吸频率为100~140次/min;CLP 24 h内死亡率可达10%,24~40 h死亡数可达30%,40~56 h死亡数可达80%。动脉血氧分压(Pa02)在12 h开始明显下降,24 h以后有恶化趋势,Pa02持续低于10 kPa,外周血白细胞计数从12 h开始降低,24 h明显降低。术后24 h已经表现出急性肺损伤。肺组织NF-κB表达活跃。动物于2 d左右出现大量死亡;给药组动物治疗和预防症状有缓解,预防组的最终死亡率为40%,治疗组为60%,肺组织NF-κB表达程度均较模型组低。结论在肺损伤早期联合应用NF-κB活化阻断剂进行预防,有助于提高ALI的存活率,能减缓肠源性肺损伤的发生和进展,减轻急性肺损伤症状,进而发挥阻止病程向多器官功能衰竭发展的重要作用,这种作用机制可能是通过抑制NF-κB活化实现的。更多还原

【Abstract】 Objective To investigate whether NF-κB blocker exerts preventive and therapeutic effects on animal models of acute lung injury（ALI）and to explore the mechanisms of theraputic action of the blocker of nuclear factor-kappaB（NF-κB） on enterogenic acute lung injury.Method The acute lung injury（ALI） animal model was created by cecal ligationperforation（CLP）.160 guinea-pigs were included in this study and randomly divided into the following groups:（1）CLP model group（n=40）;（2）The prevention group（n=40）: CLP model plus buprofen,a NF-κB blocker,in a dose of 167 mg/kg,p.o.and Vitamin E（Tocopherol） in a dose of 174mg/kg,i.m.,administred 15 days before operation;（3） The treatment group（n =40）: CLP model plus the drugs administered twice before operation and 6 h,12 h,18 h after operation.（4） Sham CLP group（n = 40）.Artery blood gases,peripheral blood leukocytes count,wet/dry weight ratio of the lungs were tested,and cells with NF-κB expression in the lungs were assessed by morphometry.Results\ In the CLP model,tachypnea,crispation,irritation occurred gradually after 6 h,some foam sputum overflowed from the nose,respirtory distress,lassitude,poor activity were observed after 16 h and even worsen after 24 h,all presented symptoms of ALI.The respiration rate ranged from 100 to 140 times/min.The mortality was 10% within 24 h,30% at 24 h～40 h and 80% at 40 h～56 h.Artery blood oxygen pressure（PaO₂） was obviously decreased after 12 h and was deteriorating and decreased to less than 10 kPa after 24 h.Peripheral blood leukocytes count began to decrease after 12 h and considerably decreased after 24 h.NF-κB expressing cells were present in the lungs.It led to septic shock and a large number of animals died around 2 days.The symptoms of the treatment group animals showed to be slightly relieved and the final mortality was 60%.The number of NF-κB expressing cells in the treatment group was lower than that in the CLP model.Conclusion The treatment with NF-κB blocker showed benefits to relieve ALI symptoms,to decelerate the enterogenic ALI process,to prevent the disease course progressing to multiple system organ failure（MSOF） and to improve the survival rate.Treatment combined with NF-κB blockers at the early stage of ALI may be an effective measure and likely to be realized through the activation of NF-κB.更多还原