薯蓣皂苷减轻脂多糖诱导的急性肺损伤中的炎症反应、氧化应激和Th17/Treg细胞失平衡

Dioscin alleviates inflammatory response,oxidative stress and Th17/Treg cell imbalance in lipopolysaccharide induced acute lung injury

目的探索薯蓣皂苷对脂多糖(lipopolysaccharide,LPS)诱导的大鼠急性肺损伤的潜在保护作用及其生物学机制。方法用LPS(5 mg/kg)诱导大鼠急性肺损伤模型,随后给予100 mg/kg或400 mg/kg薯蓣皂苷治疗3 d。治疗结束后,通过肺组织学变化、肺水肿水平、氧化应激水平、标志性细胞因子、免疫细胞标记物表达的变化评估薯蓣皂苷的干预效果。结果LPS刺激后,大鼠肺组织肺泡壁增厚,充血和中性粒细胞浸润显著,并伴有肺水肿,氧化应激水平增强,同时促炎细胞因子增加而抑炎细胞因子水平下降,应用薯蓣皂苷可改善上述变化。同时,薯蓣皂苷可抑制LPS诱导的Th17细胞特异性转录因子维甲酸相关孤核受体γt水平上升和上调Treg细胞标记叉头框蛋白P3表达。结论薯蓣皂苷可能通过抗炎、抗氧化和抑制Th17/Treg细胞失平衡减轻LPS引起的大鼠急性肺损伤。

Objective To explore the potential protective effect and biological mechanism of dioscin on lipopolysaccharide(LPS)-induced acute lung injury in rats.Methods A rat model of acute lung injury was induced by LPS(5 mg/kg),then,100 mg/kg or 400 mg/kg of dioscin was administered for 3 days.After treatment,the effect of dioscin intervention was evaluated by the changes of lung histology,pulmonary edema level,oxidative stress level,the expression of landmark cytokines and immune cell markers.Results After LPS stimulation,the alveolar walls of rat lung tissue were thickened,with remarkable congestion and neutrophil infiltration,accompanied by pulmonary edema,enhanced oxidative stress,and increased pro-inflammatory cytokines and decreased anti-inflammatory cytokines;however,dioscin could improve the above changes.Meanwhile,dioscin down-regulated the expression of Th17 cell specific transcription factor retinoic acid-related orphan receptorγt(RORγt)and up-regulated the expression of Treg cell mark forkhead box P3(Foxp3).Conclusion Dioscin reduces LPS-induced acute lung injury in rats may by anti-inflammatory,antioxidant,inhibiting RORγt expression and promoting Foxp3 expression.