尼达尼布对脂多糖致大鼠ARDS的NF-κB表达及支气管肺泡灌注液中PCⅢ水平的影响

Effects of Nintedanib on NF-κB expression in lung tissue and PCⅢ level in bronchoalveolar lavage fluid induced by lipopolysaccharide-induced ARDS in rats

目的:尼达尼布对脂多糖致大鼠急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)的核转录因子(nuclear factorκB,NF-κB)表达及支气管肺泡灌注液中Ⅲ型前胶原(procollagen typeⅢ,PCⅢ)水平的影响。方法:选择健康SD大鼠40只,将其随机分成对照组、A组、B组以及C组,每组均为10只。A组、B组及C组大鼠造模成功。对照组、A组大鼠仅注入生理盐水,B组大鼠早期在实验第7天给予尼达尼布,C组大鼠早期在实验第14天给予尼达尼布。观察4组大鼠的肺组织NF-κB表达水平、血浆β内啡肽(β-enkorphin,β-EP)及支气管肺泡灌注液中PCⅢ水平等。结果:各组之间的肺组织NF-κB阳性细胞表达率、血浆β-EP存在明显差异,具有统计学意义(F=18.493、14.581,P<0.05)。与对照组相比,A组、B组和C组的肺组织NF-κB阳性细胞表达率明显、血浆β-EP更高,差异有统计学意义(t=35.826、25.272、26.975,22.384、8.795、12.876,P<0.05),与A组相比,B组、C组的肺组织NF-κB阳性细胞表达率、血浆β-EP明显更低,差异有统计学意义(t=16.273、9.019,8.574、12.890,P<0.05),与B组相比,C组患者的肺组织NF-κB阳性细胞表达率、血浆β-EP明显更高,差异有统计学意义(t=5.711,5.692,P<0.05)。在第7、第14及第28天,4组之间存在明显差异(P<0.05)。与对照组相比,A组、B组及C组的第7、第14及第28天的PCⅢ含量明显更高,差异有统计学意义(P<0.05),与A组相比,B组、C组第7、第14及第28天的PCⅢ含量明显更低,差异有统计学意义(P<0.05),与B组相比,C组第7、第14及第28天的PCⅢ含量明显更高,差异有统计学意义(P<0.05)。结论尼达尼布对脂多糖致ARDS大鼠具有良好的保护作用,其机制可能与降低NF-κB表达、支气管肺泡灌注液中PCⅢ水平有关。

Objective： To observe effects of Nintedanib on NF-κB expression in lung tissue and PCⅢ level in bronchoalveolar lavage fluid induced by lipopolysaccharide-induced ARDS in rats. Methods： A total of 40 healthy SD rats were randomly divided into control group, group A, group B and group C, with 10 rats in each group. Rats in group A, group B and group C were successful in modeling. Rats in control group and group A were injected with saline only. Rats in group B were treated with Nintedanib at 7 days and rats in group C were treated with Nintedanib at 14 days. The expression of NF-κB in lung tissue, the level of β-EP in plasma and the level of PCⅢ in bronchoalveolar perfusion fluid were observed. Results： There were significant differences in the expression of NF-κB positive cells and plasma β-EP among groups （ F =18.493, 14.581, P 〈0.05）. Compared with the control group, the expression of NF-κB positive cells and plasma β-EP in group A, group B and group C were significantly higher than those in control group （ t =35.826, 25.272, 26.975, 22.384, 8.795, 12.876, P 〈0.05）. Compared with group A, the expression of NF-κB positive cells and plasma β-EP in group B and group C were significantly lower than those in group A （ t =16.273, 9.019, 8.574, 12.890, P 〈0.05）. Compared with group B, the expression of NF-κB positive cells and plasma β-EP in group C were significantly higher than those in group B （ t =5.711,5.692, P 〈0.05）. There was a significant difference between the 4 groups on the 7th, 14th and 28th days （ P 〈0.05）. Compared with the control group, PCⅢ levels in the 7th, 14th and 28th days in group A, group B and group C were significantly higher （ P 〈0.05）. Compared with group A, group B, group C, the content of PCⅢ on the 7th day, the 14th day and the 28th day in group C was significantly higher （ P 〈0.05）. Conclusion： Nintedanib on lipopolysaccharide-induced ARDS rats has a good protective effect, and its mechanism may be related to the reduction of NF-κB expression in bronchoalveolar perfusion solution PCⅢ level.