穿心莲内酯对脂多糖诱导的小鼠急性肺损伤中NF-κB信号通路的影响  

Effect of andrographolide on NF-κB signal pathway in lipopolysaccharide-induced acute lung injury in mice

作　　者：管弦[1] 朱涛[1] 王导新[1] 

机构地区：[1]重庆医科大学附属第二医院呼吸科,重庆400010

出　　处：《中国生物制品学杂志》2013年第4期524-527,共4页Chinese Journal of Biologicals

基　　金：国家自然科学基金(30971303)

摘　　要：目的探讨穿心莲内酯(Andrographolide,AP)对脂多糖(Lipopolysaccharide,LPS)诱导的小鼠急性肺损伤(Acute lung injury,ALI)中NF-κB信号通路的影响。方法将雄性C57BL/6小鼠随机分为3组:空白对照组、LPS组和AP+LPS组。AP+LPS组腹腔内注射10 mg/kg的AP,空白对照组腹腔内注射等体积的NS,2次/d,连续3 d,第3天注射后2 h,LPS组和AP+LPS组气管内雾化吸入LPS(1 mg/kg),空白对照组气管内雾化吸入等剂量的NS,12 h后处死小鼠,开胸取肺,10%甲醛溶液固定,随后进行石蜡切片及常规HE染色,光镜下观察各组小鼠肺组织的病理学变化;免疫组化法观察肺组织中血管细胞黏附分子-1(Vascular cell adhesion molecule-1,VCAM-1)蛋白的表达;Western blot法检测肺组织中磷酸化抑制蛋白IκB(Phospho-inhibitor ofκB,p-IκBα)和p-NF-κB(P65)蛋白的表达。结果 LPS组小鼠肺损伤明显,有明显的炎症反应;AP+LPS组小鼠肺损伤明显减轻,炎症细胞浸润明显减少。与LPS组相比,AP+LPS组小鼠肺组织中VCAM-1蛋白的表达明显抑制;p-IκBα和p-NF-κB(P65)蛋白的表达明显降低(P<0.05)。结论 AP可通过抑制磷酸化的IκBα的降解及P65单体的磷酸化来调节NF-κB通路,从而减轻小鼠肺损伤的炎症变化。Objective To investigate the effect of andrographolide（AP） on nuclear factor（NF）-κB signal pathway in lipopolysaccharide（LPS）-induced acute lung injury（ALI） in mice.Methods Male C57BL / 6 mice were randomly divided into blank control,LPS and AP ＋ LPS groups.The mice in AP ＋ LPS group were injected i.p.with 10 mg / kg AP,while those in blank control group with normal saline（NS） at an equal volume,twice a day for 3 d.Two hours after the last injection,the mice in LPS and AP ＋ LPS groups treated with LPS（1 mg / kg） by intratracheal atomizing inhalation,while those in blank control group with NS at an equal volume.The mice in various groups were killed 12 h after atomizing inhalation,of which the lungs were fixed with 10% formaldehyde solution,prepared into paraffin sections,stained with HE,and observed for pathological change under light microscope.The expression of vascular cell adhesion molecule-1（VCAM-1） in lung tissue was observed by immunohistochemical assay,while those of phosphor-inhibitor of κB（p-IκBα） and p-NF-κB（P65） by Western blot.Results Obvious lung injury and inflammatory reaction were observed in LPS group.However,both lung injury and inflammatory cell infiltration were relieved significantly in AP ＋ LPS group.As compared with those in LPS group,the expression of VCAM-1 in lung tissue of mice in AP ＋ LPS group was inhibited,while the expression levels of p-IκBα and p-NF-κB（P65） decreased significantly（P 〈0.05）.Conclusion AP regulated the NF-κB pathway by inhibiting the degradation of phosphorylated IκBα and phosphorylation of P65 monomer so as to relieve the inflammatory change in mice with lung injury.

关 键 词：穿心莲内酯 脂多糖 急性肺损伤 NF-ΚB信号通路 

分 类 号：R563[医药卫生—呼吸系统]