Zhang Li-na, Ai Yu-hang, Gong Hua, Dai Xin-gui, Peng Liu, Liu Zhi-yong, Zhao Shuang-ping
Department of Intensive Care Unit, Central South University, Changsha, Hunan, China.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2011 Sep;23(9):559-62.
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.
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: 1×10(9)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 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 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.
The rats in three groups survived, except 1 rat died in ALI model group.Blood pH and partial pressure of arterial carbon dioxide (PaCO(2)) showed no obviously differences among three groups. Partial pressure of arterial oxygen (PaO(2) ) 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: 540.28±100.78 vs. 214.45±61.37, both P<0.05). The plasma content of TNF-α and 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 ).
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.
观察经中心静脉注入携带核因子-κB（NF-κB）抑制剂IκB基因的腺病毒对大鼠感染性急性肺损伤（ALI）的治疗作用。
采用随机数字表法，将30只无特定病原体的Sprague-Dawley（SD）大鼠随机分为三组：假手术组、ALI模型组、IκB基因治疗组，每组10只。IκB基因治疗组大鼠经中心静脉注入1 ml携带IκB基因的腺病毒（滴度：1×10⁹ pfu），假手术组和ALI模型组大鼠经中心静脉注入1 ml生理盐水。随后，ALI模型组和IκB基因治疗组大鼠经尾静脉给予1 ml脂多糖（LPS，5 mg/kg）以复制ALI模型。另一方面，假手术组大鼠经尾静脉给予1 ml生理盐水。7天后测定血气分析、肺组织湿/干重比（W/D）、血浆肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）含量以及肺组织中NF-κBp65蛋白表达，显微镜下观察肺组织病理生物学变化并计算肺损伤评分。
三组大鼠均存活，ALI模型组有1只大鼠死亡。三组间血pH值和动脉血二氧化碳分压（PaCO₂）无明显差异。动脉血氧分压（PaO₂）假手术组最高，ALI模型组最低。ALI模型组血浆TNF-α（μg/L）和IL-6（ng/L）含量明显高于假手术组（TNF-α：5.20±1.09 vs. 3.01±0.46；IL-6：540.28±100.78 vs. 214.45±61.37，均P<0.05）。IκB基因治疗组血浆TNF-α和IL-6含量明显低于ALI模型组（TNF-α：3.70±0.96 vs. 5.20±1.09，IL-6：356.49±60.58 vs. 540.28±100.78，均P<0.05），且TNF-α含量已恢复至假手术组水平。肺组织W/D比值假手术组最低（4.49±0.36），ALI模型组最高（5.78±0.43），IκB基因治疗组（5.33±0.38）低于ALI组。肺损伤评分假手术组最低（0.17±0.41），ALI模型组最高（2.29±0.76），IκB基因治疗组（1.57±0.53）低于ALI组。NF-κBp65免疫组化评分假手术组最低（1.00±0.89），ALI模型组最高（9.43±1.13），IκB基因治疗组（4.00±1.15）低于后者。上述三组各项参数差异均有统计学意义（均P<0.05）。
经中心静脉注入携带IκB基因的腺病毒使IκB基因表达增加，可降低TNF-α和IL-6等促炎因子水平，抑制NF-κB活化，减少肺水含量，减轻大鼠ALI时的肺泡塌陷和肺实变，从而改善肺损伤。
