常山酮通过CD4/NF-κB通路调控LPS诱导的大鼠急性肺损伤免疫系统紊乱

摘要

目的:探究常山酮(Halofuginone,HF)对脂多糖(Lipopolysaccharide,LPS)诱导的大鼠急性肺损伤(Acute lung injury,ALI)免疫系统紊乱的作用及机制.方法:用LPS复制大鼠ALI模型并腹腔注射HF,HE染色检测肺病理损伤情况, TUNEL 检测凋亡小体数量,ELISA检测炎症因子含量,流式细胞术检测CD14含量,Western blot检测CD14/NF-κB通路蛋白的表达.结果:HF可改善LPS诱导的肺组织损伤,并能显著抑制ALI大鼠凋亡小体的形成;同时,HF可显著抑制LPS诱导的炎症因子(IL-1β、IL-6、IL-18)的分泌;此外,HF能明显减少ALI大鼠外周血CD14+细胞含量;HF还可显著下调CD14/NF-κB通路标记蛋白(CD14、TLR4、NF-κB p65)的表达.结论:HF可通过CD14/NF-κB通路调控LPS诱导的大鼠ALI免疫系统紊乱.%Objective:To evaluate the regulatory effectsand underlying mechanism of halofuginone (HF) on lipopolysaccharide (LPS)-induced immune disorder of acute lung injury (ALI) in rat. Methods: Rats were treated with LPS and HF. Subsequently,HE staining was performed for pulmonarypathological lesion,apoptosis bodies were calculated by TUNEL assay,the levels of inflammatory factors were confirmed by ELISA assay and the level of CD14 was measured by flow cytometry. Protein levels were determined by Western blot. Results: Treatment of HF dose-dependently alleviated LPS-induced pulmonary injury and inhibited the formation of apoptosis bodies significantly. Meanwhile,HF notably inhibited inflammation of ALI rats,as demonstrated by decreased IL-1β,IL-6 and IL-18. Furthermore,postconditioning with HF markedly decreased CD14+cells. Moreover,HF dose-dependently attenuated the promotive effects of LPS on CD14,TLR4 and NF-κB p65. Conclusion: HF regulates LPS-induced immune disorder of ALI in rat via CD14/NF-κB pathway.