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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。
Objective To investigate whether the activation of NF-κB plays a role in the prevention and treatment of guinea pig acute lung injury induced by cecal ligation and to explore the mechanism of NF-κB activating blockade in preventing and treating gut-derived lung injury. Methods A guinea pig model of acute lung injury was established by cecal ligation and puncture (CLP). At the same time, ibuprofen 167 mg / kg and intramuscular injection of vitamin E 174 mg / kg were given for prevention and treatment. Combined with arterial blood gas analysis, peripheral blood leukocyte count , Lung wet weight / dry weight ratio (W / D) and lung histopathological changes, immunohistochemistry method to study the activation of NF-κB in lung tissue. Results The animals in CLP group started to show symptoms slowly after 6 hours, with shortness of breath being 100-110 beats / min (normal breath of 80-95 beats / min), curled up and sensitive to external stimuli. A small amount of foamy secretions were spilled over the nasal cavity , Respiratory distress, fatigue, lying, do not like activity; 24 h respiratory distress is very significant, foam secretions (bloody) increased significantly from the nasal cavity, respiratory rate was 100 to 140 beats / min; CLP within 24 h Mortality rate of up to 10%, 24 ~ 40 h deaths up to 30%, 40 ~ 56 h deaths up to 80%. The arterial partial pressure of oxygen (Pa02) began to decline significantly at 12 h, and then worsen after 24 h. The Pa02 was continuously lower than 10 kPa. The peripheral blood leukocyte count decreased from 12 h and decreased significantly at 24 h. Acute lung injury has been demonstrated at 24 h after surgery. Lung tissue NF-κB expression is active. A large number of animals died on the 2nd day. The treatment group and the prevention symptom were relieved in the treatment group. The final mortality rate was 40% in the prevention group and 60% in the treatment group. The expression of NF-κB in the lung tissue was lower than that in the model group. Conclusions The combination of NF-κB activation blockers in the early stage of lung injury may help to improve the survival rate of ALI, reduce the incidence and progression of intestinal-derived lung injury, reduce the symptoms of acute lung injury, The role of organ failure in the development of an important role, this mechanism may be through the inhibition of NF-κB activation.