CAJ | 학술논문

目的观察经中心静脉途径注入腺病毒转载的核转录因子-kB(NF-kB)抑制因子(IkB)基因对感染性急性肺损伤(ALI)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、ALI模型组、IkB治疗组，每组10只。IkB治疗组经中心静脉注入滴度为1×109 pfu腺病毒转载的IkB基因1 ml，假手术组和模型组注人生理盐水1 ml;然后模型组和IκB治疗组经尾静脉注入脂多糖(LPS，5 mg/kg)1ml复制ALI模型，假手术组则注入生理盐水1 ml。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)、白细胞介素-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±0.46;IL-6:540.28±100.78比214.45±61.37，均P＜0.05)；IkB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±0.38)；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)，IκB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)，IκB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、II-6含量，抑制NF-κB活化，减少肺水含量和肺泡塌陷以及肺实变，从而减轻肺损伤。
목적 관찰경중심정맥도경주입선병독전재적핵전록인자-kB(NF-kB)억제인자(IkB)기인대감염성급성폐손상(ALI)적치료작용。방법 안수궤수자표법장30지SD대서분위가수술조、ALI모형조、IkB치료조，매조10지。IkB치료조경중심정맥주입적도위1×109 pfu선병독전재적IkB기인1 ml，가수술조화모형조주인생리염수1 ml;연후모형조화IκB치료조경미정맥주입지다당(LPS，5 mg/kg)1ml복제ALI모형，가수술조칙주입생리염수1 ml。관찰7d후대서적동맥혈기분석，폐습/간중(W/D)비치，혈장종류배사인자-α (TNF-α)、백세포개소-6(IL-6)함량，폐조직NF-κBp65단백표체급광경하폐조직병리개변，병계산폐손상평분。결과 모형조사망1지대서，기여대서균존활。3조간pH치、동맥혈이양화탄분압(PaCO2)비교무명현차이；동맥혈양분압(PaO2)가수술조최고，모형조최저。모형조혈장TNF-α (μg/L)、IL-6(ng/L)함량명현고우가수술조(TNF-α：5.20±1.09비3.01±0.46;IL-6:540.28±100.78비214.45±61.37，균P＜0.05)；IkB치료조혈장TNF-α화IL-6함량명현저우모형조(TNF-α.3.70±0.96비5.20±1.09;IL-6:356.49±60.58비540.28±100.78，균P＜0.05)，기중TNF-α함량이회복지가수술조수평。폐W/D비치：가수술조최저(4.49±0.36)，모형조최고(5.78±0.43)，IκB치료조거중(5.33±0.38)；폐손상평분（분）：가수술조최저（0.17±0.41），모형조최고(2.29±0.76)，IκB치료조거중（1.57±0.53）；폐NF-κB면역조화평분（분）：가수술조최저(1.00±0.89)，모형조최고(9.43±1.13)，IκB치료조거중(4.00±1.15)；상술지표3조간량량비교차이균유통계학의의(균P＜0.05)。결론 경중심정맥도경주입선병독전재적IκB기인，가강저ALI대서혈중염증인자TNF-α、II-6함량，억제NF-κB활화，감소폐수함량화폐포탑함이급폐실변，종이감경폐손상。
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 (ALI) 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 ALI 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 mllipopolysaccharide (LPS, 5 ml/kg) through tail vein to reproduce model of ALI. On the other hand, the rats of sham group were given 1 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 factor-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±1.09vs. 3. 01±0. 46; IL-6: 540. 28±100. 78 vs. 214. 45±61.37, both P＜0. 05). The plasma content of TNF-αand IL-6 in IκB 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. 49±60. 58 vs. 540. 28±100.78, both P＜0. 05), and TNF-α content had restored to the level observed in sham group. The ratio of W/D of lung was lowest in sham group (4. 49±0. 36) and highest in ALI model group (5.78±0. 43), and that of IκB gene treatment group (5. 33±0. 38)was lower than that of ALI group. The score of lung injury was lowest in sham group (0. 17±0. 41) and highest in ALI model group (2. 29±0. 76), and that of IκB gene treatment group (1. 57±0. 53) was lower than that of ALI group. The scale of NF-κBp65 immunohistochemistry was lowest in sham group (1. 00±0. 89) and highest in ALI model group (9. 43± 1.13), and that of IκB gene treatment group (4. 00± 1.15)was lower than the latter. The differences of all the above parameters in three groups were statistically significant (all P＜0. 05). Conclusion Increased expression of IκB gene by an infusion of adenovirus borne IκB gene through central vein can lower the levels of pro-inflammatory factors, such as TNF-α and IL-6,restrain the NF-κB activation, reduce lung water, alleviate alveolar collapse and lung consolidation in ALI in rats, thus lung injury is ameliorated.