盲肠结扎穿刺致豚鼠急性肺损伤及NF-κB活化阻断剂治疗作用研究  

The Therapy Effects of NF-κB Blocker on the Guinea Pigs of Acute Lung Injury Induced by Cecal Ligation-Peferation(CLP)

作　　者：李守明[1] 李岚[2] 刘志勇[3] 汪庆余[4] 邹音[1] 吴熙[1] 朱绿绮[1] 

机构地区：[1]江西省儿童医院,江西南昌330006 [2]江西医学院儿科系,江西南昌330006 [3]江西省劳卫所医学实验动物中心,江西南昌330006 [4]江西医学院第二附属医院,江西南昌330006

出　　处：《江西科学》2004年第4期255-259,264,共6页Jiangxi Science

摘　　要：研究和建立败血性急性肺损伤的动物模型,并观察联用NF＿κB活性阻断剂对肺损伤动物的治疗作用。方法:用盲肠结扎穿刺(CLP)法建立豚鼠急性肺损伤模型,同时经口给予布活芬167mg/kg和肌肉注射VitE174mg/kg,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)及肺组织病理观察,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,最后导致动物败血性休克,于2d左右出现大量死亡;给药组动物症状有所缓解,最终死亡率为60%,肺组织NF＿κB表达程度较模型组低。结论:利用CLP法可以在豚鼠上建立急性肺损伤模型,在肺损伤早期联合应用NF＿κB活化的阻断剂,有助于提高急性肺损伤(ALI)的存活率,减轻ALI症状。Objective To establish the animal model of septic acute lung injury (ALI) and to observe the therapeutic effects with the blocker of nuclear factor-kappaB (NF-κB). Method ALI animal model had been set up with CLP (cecal ligation-peferation), combinating with NF-κB blocker buprofen 167 mg/kg via mouth and Vitamin E (Tocopherol) 174 mg/kg via I.M. Artery blood gases, white cell count in peripheral blood, wet/dry weight ratio of the lungs were tested, pathologic morphometry and the cells marked with NF-κB of the lungs were observed. Results In 'CLP' animal model, tachypnea, crispation, irritation occurred gradually after 6 h, some foam sputum overflow from nose, respirtory distress, lassitude, less activity were observed after 16 h and which became much worse after 24 h, the presenting symptoms of ALI. The respiration rate ranging 100 to 140 times/min. The mortality was 10% with in 24 h,30% with in 24 h～40 h and 80% with in 40 h～56 h. Artery blood oxygen pressure (PaO2) obviously decreased after 12 h, it was deteriorating consistantly to less than 10 kPa after 24 h. White cell count in peripheral blood began to decrease after 12 h and obviously decreased after 24 h. The marked cells by NF-κB in the lungs were actively expressed. It led to septic shock and a large number of animals died around 2 days. The symptoms of the treatment group animals slightly relieved and the final mortality was 60%. The expression of NF-κB cell in treatment group was lower than that in the CLP model. Conclusion The animal model of ALI in Guinea pigs by CLP could be established. It benefits to relieve the symptom of ALI and to improve the survival rate, combination with NF-κB blockers at early stage of the ALI.

关 键 词：肺损伤 豚鼠 盲肠结扎穿刺(CLP) 核因子-ΚB 

分 类 号：R563.8[医药卫生—呼吸系统] R282.71[医药卫生—内科学]