[1]陈宏,宋倩男,张伟,等.雷公藤甲素调节Nrf2/SLC7A11/GPX4信号通路对肺成纤维细胞及铁死亡的影响[J].陕西中医,2026,(2):166-170.[doi:DOI:10.3969/j.issn.1000-7369.2026.02.004]
　CHEN Hong,SONG Qiannan,ZHANG Wei,et al.Effect of triptolide regulating Nrf2/SLC7A11/GPX4 signaling pathway on lung fibroblasts and ferroptosis[J].,2026,(2):166-170.[doi:DOI:10.3969/j.issn.1000-7369.2026.02.004]
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雷公藤甲素调节Nrf2/SLC7A11/GPX4信号通路对肺成纤维细胞及铁死亡的影响

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2026年2期
页码:
166-170
栏目:
基础研究
出版日期:
2026-02-05

文章信息/Info

Title:
Effect of triptolide regulating Nrf2/SLC7A11/GPX4 signaling pathway on lung fibroblasts and ferroptosis
作者:
陈宏1; 宋倩男2; 张伟1; 沙德香2; 王文增2; 刘皓宇2; 金甲一2; 冯大庆1; 齐鑫2; 吴国航2
（1.黑龙江中医药大学附属第一医院，黑龙江 哈尔滨 150040；2.黑龙江中医药大学，黑龙江 哈尔滨 150040）
Author(s):
CHEN Hong1; SONG Qiannan2; ZHANG Wei1; SHA Dexiang2; WANG Wenzeng2; LIU Haoyu2; JIN Jiayi2; FENG Daqing1; QI Xin2; WU Guohang2
(1.First Affiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin 150040,China;2.Heilongjiang University of Chinese Medicine,Harbin 150040,China)
关键词:
雷公藤甲素; 转化生长因子-β1; 肺成纤维细胞; 铁死亡; Nrf2/SLC7A11/GPX4信号通路
Keywords:
Triptolide; TGF-β1; Pulmonary fibroblasts; Ferroptosis; Nrf2/SLC7A11/GPX4 signaling pathway
分类号:
R 282
DOI:
DOI:10.3969/j.issn.1000-7369.2026.02.004
文献标志码:
A
摘要:
目的：探究雷公藤甲素（TPL）抑制转化生长因子-β1（TGF-β1）诱导的肺成纤维细胞向肺肌成纤维细胞转化的作用机制，及调节Nrf2/SLC7A11/GPX4信号通路对铁死亡的影响。方法：C57BL/6小鼠肺成纤维细胞，经细胞培养，饥饿24 h后，给予不同处理。对照组不添加任何诱导及干预药物，模型组加入浓度为2.5 ng/ml的TGF-β1进行诱导处理，不同剂量TPL组在加入浓度为2.5 ng/ml的TGF-β1诱导的同时，分别加入雷公藤甲素低剂量（0.25 mg/kg）、雷公藤甲素中剂量（0.50 mg/kg）、雷公藤甲素高剂量（1.00 mg/kg）进行干预处理，在指定时间收取细胞。应用流式细胞术检测细胞凋亡率，胶原胶收缩法、细胞免疫荧光法等检测TPL抑制TGF-β1诱导的肺成纤维细胞转化指标的变化情况，应用Western blot法测定铁死亡通路相关基因Nrf2、溶质载体家族7成员11（SLC7A11）、GPX4的表达水平。结果：TPL能下调肺成纤维细胞转化过程中α-平滑肌肌动蛋白表达量（P＜0.05），同时能够有效抑制细胞肌丝的产生，并减弱肺成纤维细胞对胶原胶的收缩能力。与对照组比较，其余各组细胞凋亡率升高（P＜0.05）。与TGF-β1组比较，雷公藤甲素高剂量组、雷公藤甲素中剂量组和雷公藤甲素低剂量组细胞凋亡率降低（P＜0.05）。与雷公藤甲素中剂量组和雷公藤甲素低剂量组比较，雷公藤甲素高剂量组细胞凋亡率降低（P＜0.05）。TPL显著升高肺组织中Nrf2、GPX4和SLC7A11的表达水平（P＜0.05），且与雷公藤甲素中、低剂量组相比，雷公藤甲素高剂量组铁死亡相关指标Nrf2、GPX4、SLC7A11表达量更高（P＜0.05）。结论：TPL能抑制肺成纤维细胞转化，抑制TGF-β1诱导的肺成纤维细胞凋亡，TPL通过调节Nrf2/SLC7A11/GPX4信号通路抑制铁死亡并有效缓解小鼠肺纤维化。
Abstract:
Objective:To explore mechanism by which triptolide (TPL) inhibits transformation of lung fibroblasts into myofibroblasts induced by transforming growth factor-β1 (TGF-β1),and its effect on ferroptosis through regulating the Nrf2/SLC7A11/GPX4 signaling pathway.Methods:C57BL/6 mouse lung fibroblasts were cultured and starved for 24 hours,then subjected to different treatments.The control group was not supplemented with any inducing or interfering drugs.The model group were treated with TGF-β1 at a concentration of 2.5 ng/ml for induction.Different doses of TPL groups were treated with TGF-β1 at a concentration of 2.5 ng/ml for induction and were respectively supplemented with low-dose triptolide (0.25 mg/kg),medium-dose triptolide (0.50 mg/kg),and high-dose triptolide (1.00 mg/kg) for intervention.Cells were collected at the designated time.Flow cytometry was used to detect the apoptosis rate of cells,and collagen gel contraction and cell immunofluorescence methods were used to detect changes in the transformation indicators of lung fibroblasts induced by TGF-β1 inhibited by TPL.Western blot was used to determine the expression levels of Nrf2,solute carrier family 7 member 11 (SLC7A11),and GPX4,which were related to the ferroptosis pathway.Results:TPL could down-regulate the expression of α-smooth muscle actin during the transformation of lung fibroblasts (P＜0.05),and effectively inhibit production of myofilaments and weaken contraction ability of lung fibroblasts on collagen gel.Compared with the control group,the apoptosis rate of cells in the other groups increased (P＜0.05).Compared with the TGF-β1 group,the apoptosis rate of cells in the high-dose,medium-dose,and low-dose triptolide groups decreased (P＜0.05).Compared with the medium-dose and low-dose triptolide groups,the apoptosis rate of cells in the high-dose triptolide group decreased (P＜0.05).TPL significantly increased expression levels of Nrf2,GPX4,and SLC7A11 in lung tissue (P＜0.05),and the expression levels of Nrf2,GPX4,and SLC7A11 related to ferroptosis in the high-dose triptolide group were higher than those in the medium-dose and low-dose triptolide groups (P＜0.05).Conclusion:TPL can inhibit the transformation of lung fibroblasts,inhibit the apoptosis of lung fibroblasts induced by TGF-β1,and effectively alleviate pulmonary fibrosis in mice by regulating the Nrf2/SLC7A11/GPX4 signaling pathway and inhibiting ferroptosis.

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备注/Memo

备注/Memo:
中国博士后科学基金第13批特别资助项目（2020T130178）；黑龙江省自然科学基金资助项目（LH2023H074）;黑龙江省卫生健康委员会课题（20230202040115）
更新日期/Last Update: 2026-02-09