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

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. Key words: Acute lung injury ;  Nuclear factor-κB ;  Gene therapy ;  Inhibitor of nuclear factor-κB ;  Adenoviruses ;