中药新药与临床药理2025,Vol.36Issue(11):1849-1860,12.DOI:10.19378/j.issn.1003-9783.2025.11.004
炎调方通过调控NF-κB/LncRNA-Miat信号通路抑制肺泡Ⅱ型上皮细胞过度自噬减轻肠缺血再灌注引起的肺损伤
Yan Tiao Formula Attenuates Intestinal Ischemia-Reperfusion-Induced Lung Injury by Suppressing Excessive Autophagy in Alveolar Type Ⅱ Epithelial Cells via Regulating the NF-κB/LncRNA-Miat Signaling Pathway
摘要
Abstract
Objective To investigate the mechanism by which Yan Tiao Formula inhibits excessive autophagy in alveolar type Ⅱ epithelial cells(AEC Ⅱ)and alleviates acute lung injury induced by intestinal ischemia-reperfusion(IIR),with a focus on the NF-κB/long non-coding RNA myocardial infarction-associated transcript(LncRNA-Miat)signaling pathway.Methods An in vitro hypoxia-reoxygenation model was established and treated with Yan Tiao Formula.A stable NF-κB knockdown cell line was generated using lentiviral transfection,with knockdown efficiency confirmed by Western Blot and quantitative real-time PCR(RT-qPCR).Protein and mRNA expression levels were detected by Western Blot and RT-qPCR,respectively.Autophagy was assessed by monodansylcadaverine(MDC)staining.Results Compared with the negative control(shNC)group,the shNF-κB group showed significantly reduced NF-κB protein and mRNA expression(P<0.001,P<0.000 1).Compared with the control group,the hypoxia-reoxygenation group exhibited enhanced autophagy(P<0.01,P<0.001)and increased LC3II protein expression(P<0.05).Compared with the hypoxia-reoxygenation group,the Yan Tiao Formula group and Yan Tiao Formula+hypoxia-reoxygenation group showed significantly suppressed autophagy(P<0.05,P<0.01,P<0.001)and decreased LC3II and p62 protein expression(P<0.05,P<0.01).Compared with the control group,the hypoxia-reoxygenation group exhibited elevated NF-κB mRNA and protein levels,as well as LncRNA-Miat mRNA expression(P<0.05,P<0.01).Compared with the hypoxia-reoxygenation group,the Yan Tiao Formula group and Yan Tiao Formula+hypoxia-reoxygenation group showed reduced NF-κB mRNA and protein levels,as well as LncRNA-Miat mRNA expression(P<0.05,P<0.01,P<0.001).After NF-κB knockdown,the shNC+hypoxia-reoxygenation group showed increased autophagy in AEC II(P<0.05)and elevated LC3II protein expression(P<0.05)compared with the shNC group.In contrast,the shNF-κB group and shNF-κB+hypoxia-reoxygenation group exhibited reduced autophagy in AEC II(P<0.05,P<0.01,P<0.001)and decreased LC3II protein expression(P<0.05)compared with the shNC+hypoxia-reoxygenation group.The shNC+hypoxia-reoxygenation group also showed increased LncRNA-Miat mRNA expression compared with the shNC group(P<0.05),while the shNF-κB group and shNF-κB+hypoxia-reoxygenation group showed decreased LncRNA-Miat mRNA expression compared with the shNC+hypoxia-reoxygenation group(P<0.05,P<0.01).Conclusion Yan Tiao Formula attenuates acute lung injury following IIR by inhibiting excessive autophagy in AEC II through the NF-κB/LncRNA-Miat signaling pathway.关键词
炎调方/NF-κB/LncRNA-Miat信号通路/肺泡Ⅱ型上皮细胞/过度自噬/肠缺血再灌注/急性肺损伤Key words
Yan Tiao Formula/NF-κB/LncRNA-Miat signaling pathway/AEC Ⅱ/excessive autophagy/intestinal ischemia-reperfusion/acute lung injury分类
医药卫生引用本文复制引用
陈天阳,严佳,诸炳骅,唐昱天,韩丹,方荣,王倩..炎调方通过调控NF-κB/LncRNA-Miat信号通路抑制肺泡Ⅱ型上皮细胞过度自噬减轻肠缺血再灌注引起的肺损伤[J].中药新药与临床药理,2025,36(11):1849-1860,12.基金项目
国家自然科学基金项目(82074156). (82074156)