经中心静脉途径注入腺病毒转载的核转录因子-κB抑制因子基因治疗大鼠感染性急性肺损伤  

The experiment study of treatment of infectious acute lung injury by intravenous administration of adenovirus borne inhibitor of nuclear factor-κB gene in rat

作　　者：张丽娜[1] 艾宇航[1] 龚华[1] 戴新贵[1] 彭鎏[1] 刘志勇[1] 赵双平[1] 

机构地区：[1]中南大学湘雅医院ICU,湖南长沙410008

出　　处：《中国危重病急救医学》2011年第9期559-562,共4页Chinese Critical Care Medicine

基　　金：湖南省自然科学基金资助项目（05JJ40046）

摘　　要：目的观察经中心静脉途径注入腺病毒转载的核转录因子-κB（NF-κB）抑制因子（1wB）基因对感染性急性肺损伤（ALl）的治疗作用。方法按随机数字表法将30只SD大鼠分为假手术组、ALl模型组、IgB治疗组，每组10只。InB治疗组经中心静脉注入滴度为1×10^9pfu腺病毒转载的I”B基因1ml，假手术组和模型组注入生理盐水1ml；然后模型组和IgB治疗组经尾静脉注入脂多糖（LPS，5mg／kg）1ml复制ALI模型，假手术组则注人生理盐水1m1。观察7d后大鼠的动脉血气分析，肺湿／干重（W／D）比值，血浆肿瘤坏死因子-α（TNF-α）、自细胞介素-6（IL-6）含量，肺组织NF-κBp65蛋白表达及光镜下肺组织病理改变，并计算肺损伤评分。结果模型组死亡1只大鼠，其余大鼠均存活。3组间pH值、动脉血二氧化碳分压（PaCO2）比较无明显差异；动脉血氧分压（PaO2）假手术组最高，模型组最低。模型组血浆TNF-α（μg／L）、IL-6（ng／L）含量明显高于假手术组（TNF-α：5．20±1．09比3．01土0．46；IL-6：540．28±100．78比214．45±61．37，均P〈0．05）；IgB治疗组血浆TNF-α和IL-6含量明显低于模型组（TNF-α：3．70±0．96比5．20±1．09；IL-6：356．49±60．58比540．28±100．78，均P〈0．05），其中TNF-α含量已恢复至假手术组水平。肺W／D比值：假手术组最低（4．49±0．36），模型组最高（5．78±0．43），IκB治疗组居中（5．33±0．a8）；肺损伤评分（分）：假手术组最低（0．17±0．41），模型组最高（2．29±0．76），IKB治疗组居中（1．57±0．53）；肺NF-κB免疫组化评分（分）：假手术组最低（1．00±0．89），模型组最高（9．43±1．13），IxB治疗组居中（4．00±1．15）；上述指标3组间两两比较差异均有统计学意义（均P〈0．05）。结论经中心静脉途径注入腺病毒转载的IκB基因，可降低ALI大鼠血中炎症因子TNF-α�Objective To observe the effects of adenovirus borne IκB gene, an inhibitor of nuclear factor-κB （NF-κB）, infused via central vein, to treat infectious acute lung injury （ALl） in rats. Methods According to random number table method, 30 pathogen-free Sprague-Dawley （SD） rats were randomly divided into three groups： sham group, ALI model group, IκB gene treatment group, with 10 rats in each group. The rats of IκB gene treatment group were infused 1 ml adenovirus borne IκB gene （titre： 1 × 109 pfu）, the rats of sham group and ALl model group were infused 1 ml normal saline through central vein. Subsequently, the rats of ALI model group and the IκB gene treatment group were given 1 ml lipopolysaccharide （LPS, 5 ml/kg） through tail vein to reproduce model of ALI. On the other hand, the rats of sham group were given I ml normal saline through tail vein. Blood gas analysis, the ratio of wet to dry weight （W/D） of lung, plasma contents of tumor necrosis faetor-α （TNF-α） and interleukin-6 （IL-6）, and protein expression of NF-κBp65 in lung tissue were determined, the pathobiological changes in lung tissue were microscopically observed and the scores of lung injury were calculated after 7 days. Results The rats in three groups survived, except 1 rat died in ALI model group. Blood pH and partial pressure of arterial carbon dioxide （PaCO2） showed no obviously differences among three groups. Partial pressure of arterial oxygen （PaO2） was highest in sham group and the lowest in ALI model group. The plasma content of TNF-α （μg/L） and IL-6 （ng/L） in ALI model group were obviously higher than those in sham group （TNF-α： 5.20±1.09 vs. 3. 01±0.46 IL-6： 540. 281100.78 vs. 214.45±61.37, both P〈0.05）. The plasma content of TNF-α and IL-6 in IeB gene treatment group were obviously lower than those in ALI model group （TNF-α： 3.70± 0. 96 vs. 5.20±1.09, IL-6： 356. 491±60. 58 vs. 540. 28±100. 78, both P〈0. 05）, and TNF-α content had restored to

关 键 词：肺损伤 急性 核转录因子-ΚB 基因治疗 核转录因子-κB抑制因子 腺病毒 

分 类 号：R563[医药卫生—呼吸系统]