NF-κB活化阻断剂对盲肠结扎穿刺所致豚鼠急性肺损伤的预防与治疗  

Preventive and Therapeutic Effects of NF-κB on Guinea-pig Acute Lung Injury Model Induced By Cecal Ligation-Perforation(CLP)

作　　者：李守明[1] 刘志勇[2] 李岚[3] 陈霞[1] 连惠红[1] 汪庆余[4] 张淑正[1] 邹音[1] 吴熙[1] 朱绿绮[1] 李翠昌[1] 

机构地区：[1]江西省儿童医院,南昌330006 [2]江西省劳动卫生职业病防治研究所实验动物中心 [3]江西医学院儿科系 [4]江西医学院第二附属医院病理科

出　　处：《中国比较医学杂志》2006年第2期89-92,I0002,共5页Chinese Journal of Comparative Medicine

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167mg／kg和肌内注射维生素E174mg／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／下重比值（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6h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；16h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；24h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；CLP24h内死亡率可达10％，24-40h死亡数可达30％，40～56h死亡数可达80％。动脉血氧分压（PaO2）在12h开始明显下降，24h以后有恶化趋势，PaO2持续低于10kPa，外周血白细胞计数从12h开始降低，24h明显降低。术后24h已经表现出急性肺损伤。肺组织NF-κB表达活跃。动物于2d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。Objective To investigate whether NF-κB blocker exerts preventive and therapeutic effects on animal models of acute lung injury（ALl）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 ligation-perforation （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 women 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 ceils 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%. Tbe number of NF-κB expressing cells in the treatment group was lower than that in the CLP mode

关 键 词：NF-κB活化阻断剂 肺损伤 败血性 豚鼠 盲肠结扎穿刺 

分 类 号：R392[医药卫生—免疫学]