摘要
目的:探讨姜黄素调节MAPK/NF-κB信号通路对急性呼吸窘迫综合征(ARDS)小鼠发挥保护作用。方法:BALB/C小鼠随机分为对照组、模型组、姜黄素(200mg/kg)组、茴香霉素(MAPK激活剂,20mg/kg)组、姜黄素(200mg/kg)+茴香霉素(20mg/kg)组,每组12只,模型组和药物干预组小鼠通过气管滴注脂多糖来建立ARDS模型,对照组小鼠气管滴注等量生理盐水,分组干预各组小鼠3d后检测其肺功能指标:用力肺活量(FVC)、呼气峰流值(PEF)、氧合指数(oxygenation index,OI);检测各组小鼠肺泡灌洗液(BALF)中炎性细胞数;HE染色检测各组小鼠肺组织病理形态并进行病理评分;ELISA法检测各组小鼠BALF与血清炎性细胞相关因子TNF-α、IL-1β、IL-10、IL-13水平;蛋白免疫印迹法检测各组小鼠肺组织MAPK/NF-κB通路蛋白表达。结果:与对照组比较,模型组小鼠炎性细胞数、肺组织病理评分、TNF-α与IL-1β水平、p-p38 MAPK/p38 MAPK、p-NF-κB p65/NF-κB p65显著升高(P<0.05),FVC、PEF、OI、IL-10与IL-13水平显著降低(P<0.05)。与模型组比较,姜黄素组小鼠炎性细胞数、肺组织病理评分、TNF-α与IL-1β水平、p-p38 MAPK/p38 MAPK、p-NF-κB p65/NF-κB p65降低(P<0.05),FVC、PEF、OI、IL-10与IL-13水平升高(P<0.05);茴香霉素组小鼠炎性细胞数、肺组织病理评分、TNF-α与IL-1β水平、p-p38 MAPK/p38 MAPK、p-NF-κB p65/NF-κB p65升高(P<0.05),FVC、PEF、OI、IL-10与IL-13水平降低(P<0.05)。与姜黄素组比较,姜黄素+茴香霉素组小鼠炎性细胞数、肺组织病理评分、TNF-α与IL-1β水平、p-p38 MAPK/p38 MAPK、p-NF-κB p65/NF-κB p65升高(P<0.05),FVC、PEF、OI、IL-10与IL-13水平降低(P<0.05)。结论:姜黄素可通过阻止MAPK/NF-κB信号激活而抑制ARDS小鼠炎症,进而减轻其肺组织炎性损伤,改善其肺功能,最终对其发挥明显肺保护作用。
Objective:To investigate the protective effects of curcumin on acute respiratory distress syndrome(ARDS)in mice by regulating the MAPK/NF-κB signaling pathway.Methods:BALB/C mice were randomly divided into five groups:control group,model group,curcumin group(200mg/kg),anisomycin group(MAPK activator,20mg/kg),and curcumin(200mg/kg)+anisomycin(20mg/kg)group,with 12 mice per group.ARDS models were established in the model and drug intervention groups via intratracheal instillation of lipopolysaccharide(LPS),while the control group received an equal volume of normal saline.After 3 days of intervention,the following were measured:lung function indices-forced vital capacity(FVC),peak expiratory flow(PEF),and oxygenation index(OI);inflammatory cell count in bronchoalveolar lavage fluid(BALF);histopathological changes and lung injury scores in lung tissues via HE staining;levels of TNF-α,IL-1β,IL-10,and IL-13 in BALF and serum using ELISA;and MAPK/NF-κB pathway protein expression in lung tissues via Western blotting.Results:Compared with the control group,the model group showed significantly increased inflammatory cell count,lung injury score,TNF-αand IL-1βlevels,and p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 ratios(P<0.05),while FVC,PEF,OI,IL-10,and IL-13 levels were significantly decreased(P<0.05).Compared with the model group,the curcumin group had reduced inflammatory cell count,lung injury score,TNF-αand IL-1βlevels,and p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 ratios(P<0.05),along with increased FVC,PEF,OI,IL-10,and IL-13 levels(P<0.05).The anisomycin group,compared to the model group,exhibited further increases in inflammatory markers and reductions in lung function indices.Co-administration of curcumin and anisomycin negated the protective effects observed in the curcumin group alone.Conclusion:Curcumin inhibits the activation of the MAPK/NF-κB signaling pathway,reducing inflammation,mitigating lung tissue damage,and improving lung function in ARDS mice,thereby exerting a significant protective effect on the lungs.
作者
胡畔
张卓
HU Pan;ZHANG Zhuo(Hubei Hospital of Traditional Chinese Medicine,Hubei Wuhan 430001,China)
出处
《河北医学》
CAS
2024年第10期1621-1627,共7页
Hebei Medicine
基金
湖北省武汉市中医药科研项目,(编号:NO.WZ22C58)。
作者简介
通讯作者:张卓。
