大黄素通过NF-κB信号通路改善香烟烟雾提取物诱导的人支气管上皮细胞损伤  

Emodin via the NF-κB signaling pathway ameliorate human bronchial epithelial cell injury induced by cigarette smoke extract

作　　者：王欢 张暮盈 WANG Huan;ZHANG Muying(Department of Pulmonary Disease,Xi′an Hospital of Traditional Chinese Medicine,Xi′an,Shanxi 710021,China;Respiratory and Critical Care Medicine,Affiliated Hospital of Shanxi University of Traditional Chinese Medicine,Xianyang,Shanxi 712000,China)

机构地区：[1]西安市中医医院肺病科,陕西西安710021 [2]陕西中医药大学附属医院呼吸与危重症医学科,陕西咸阳712000

出　　处：《临床肺科杂志》2025年第3期383-389,共7页Journal of Clinical Pulmonary Medicine

摘　　要：目的探讨大黄素对香烟烟雾提取物(CSE)诱导的人支气管上皮细胞损伤的作用及机制。方法培养人支气管上皮细胞16HBE,使用CSE和不同剂量的大黄素处理细胞,分成对照组、模型组(使用CSE进行诱导)、大黄素低剂量组(CSE诱导+20μg/mL大黄素)、大黄素中剂量组(CSE诱导+40μg/mL大黄素)、大黄素高剂量组(CSE诱导+80μg/mL大黄素);CCK8实验检测细胞活力;ELISA试剂盒检测SOD、MDA、TNF-α、IL-6水平;流式细胞术检测细胞凋亡情况;铁离子试剂盒检测细胞铁离子水平;Western Blot检测铁死亡相关蛋白GPX4以及NF-κB信号通路相关蛋白P65和p-P65蛋白表达。结果与对照组比较,模型组细胞活力显著下降(P<0.001),细胞培养液上清中MDA、IL-6、TNF-α以及细胞中细胞凋亡率及铁离子水平明显升高(P<0.001),细胞中GPX4蛋白水平降低(P<0.001),p-P65蛋白表达升高(P<0.001);与模型组比较,大黄素低、中、高剂量组均可增加细胞活力(P<0.05或P<0.001),降低细胞培养液上清中MDA、IL-6、TNF-α及细胞中细胞凋亡率和铁离子水平(P<0.01或P<0.001),促进GPX4蛋白表达(P<0.05或P<0.001),抑制p-P65蛋白表达(P<0.001),以上作用呈剂量依赖性。结论大黄素可能通过抑制NF-κB信号通路抑制CSE诱导的16HBE氧化应激、炎症反应、凋亡和铁死亡,提高细胞活力,进而改善CSE诱导的慢阻肺。Objective To investigate the effect and mechanism of emodin on human bronchial epithelial cell injury induced by cigarette smoke extract(CSE).Methods Cultured human bronchial epithelial cells 16HBE,treated with CSE and different doses of emodin,and they were divided into control group,model group(CSE induction),emodin low-dose group(CSE induction+20μg/mL emodin),emodin medium-dose group(CSE induction+40μg/mL emodin),and emodin high-dose group(CSE induction+80μg/mL emodin).Cell viability was detected by CCK8 assay.The levels of SOD,MDA,TNF-α,and IL-6 were detected by the ELISA kit.The apoptosis was detected by flow cytometry.Iron ion level was detected by the iron ion kit.Western blot analysis of iron death-related protein GPX4 and NF-κB signaling pathway-related proteins P65 and p-P65 protein expression were detected.Results Compared with the control group,the cell viability in the model group was significantly decreased(P<0.001),MDA,IL-6,TNF-α in the supernatant of the cell culture medium,apoptosis rate and iron ion level in the cells were significantly increased(P<0.001),and the GPX4 protein level in the cells was decreased(P<0.001),p-P65 protein expression was increased(P<0.001);Compared with model group,emodin low-dose,medium-dose and high-dose groups could increase the cell viability(P<0.05 or P<0.001),decrease MDA,IL-6,TNF-αin cell culture medium supernant,apoptosis rate and iron ion level in cells(P<0.01 or P<0.001),promote GPX4 protein expression(P<0.05 or P<0.001),and inhibit p-P65 protein expression(P<0.001)in a dose-dependent manner.Conclusion Emodin may inhibit 16HBE oxidative stress,inflammation,apoptosis,and iron death induced by CSE through the inhibition of NF-κB signaling pathway,improve cell viability,and thus ameliorating CSE-induced COPD.

关 键 词：大黄素 慢性阻塞性肺疾病 NF-ΚB信号通路 支气管上皮细胞 

分 类 号：R563.9[医药卫生—呼吸系统]