柴胡皂苷D抑制TGF-β1诱导的人胚肺成纤维细胞系HFL1纤维化相关蛋白的表达

doi:10.16352/j.issn.1001-6325.2026.02.0241

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (2): 241-249.doi: 10.16352/j.issn.1001-6325.2026.02.0241

柴胡皂苷D抑制TGF-β1诱导的人胚肺成纤维细胞系HFL1纤维化相关蛋白的表达

闵锐^1*, 李妲¹, 徐豫湘²

湖南中医药大学第一附属医院 1.呼吸科; 2.风湿免疫科,湖南长沙 410007

收稿日期:2025-03-04 修回日期:2025-06-23 出版日期:2026-02-05 发布日期:2026-01-21
通讯作者: ^* m856458@163.com
基金资助:
长沙市自然科学基金(kq2202455)

Saikosaponin D inhibits TGF-β1-induced expression of fibrosis-related proteins in HFL1 human fetal lung fibroblasts

MIN Rui^1*, LI Da¹, XU Yuxiang²

1. Department of Respiratory Medicine; 2. Department of Rheumatology and Immunology, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410007, China

Received:2025-03-04 Revised:2025-06-23 Online:2026-02-05 Published:2026-01-21
Contact: ^* m856458@163.com

摘要/Abstract

摘要： 目的探究柴胡皂苷D(SSD)对特发性肺纤维化(IPF)的治疗作用。方法将人胚肺成纤维细胞系(HFL1)分为对照组、模型组(TGF-β1 5 ng/mL)以及SSD干预模型组(2.5/5/10 μmol/L)和阳性对照组(20 nmol/L雷帕霉素)。通过CCK8法检测细胞增殖;Western blot检测细胞纤维化和细胞焦亡相关蛋白质表达;RT-qPCR检测纤维化相关基因表达;LDH释放实验检测细胞损伤;流式细胞术检测细胞凋亡情况;免疫荧光技术检测细胞焦亡相关蛋白表达水平;通过显微镜观察细胞焦亡情况。结果与对照组相比,TGF-β1显著促进HFL1细胞增殖(P＜0.05);与模型组相比,SSD呈浓度依赖性抑制细胞增殖(P＜0.05)。与对照组相比,模型组mTORC1/4E-BP1通路关键蛋白及焦亡相关蛋白表达显著升高(P＜0.05);与模型组相比,SSD组上述蛋白表达均显著降低(P＜0.05)。与对照组相比,模型组fibronectin、collagen I、IL-1β和IL-18 mRNA表达显著升高(P＜0.05);与模型组相比,SSD治疗组上述基因表达显著降低(P＜0.05)与对照组相比,模型组LDH释放显著增加(P＜0.05);与模型组相比,SSD组LDH释放显著减少(P＜0.05)。免疫荧光检测:与对照组相比,模型组Ki67和vimentin表达显著升高(P＜0.05);与模型组相比,SSD治疗组Ki67和vimentin表达显著降低(P＜0.05)。结论 SSD可能降低细胞焦亡和纤维化相关蛋白表达,减少炎性因子释放,从而减轻TGF-β1诱导的肺纤维化进程。

关键词: 柴胡皂苷D, 细胞焦亡, 肺纤维化

Abstract: Objective To investigate the therapeutic effects of saikosaponin D (SSD) on idiopathic pulmonary fibrosis(IPF). Methods Human fetal lung fibroblasts HFL1 cells were divided into control, model (TGF-β1, 5 ng/mL), SSD intervention (2.5/5/10 μmol/L), and positive control (rapamycin, 20 nmol/L) groups. Cell proliferation was assessed by CCK-8 assay; the expression of fibrosis- and pyroptosis-related protein were determined by Western blot; the expression of fibrosis-related genes was measured by RT-qPCR; cell damage was evaluated by LDH release assay; apoptosis was examined by flow cytometry; pyroptosis-related protein level was detected by immunofluorescence method and pyroptosis was observed by microscopy. Results Compared with the control group, TGF-β1 significantly promoted HFL1 cell proliferation (P＜0.05); compared with the model group, SSD inhibited cell proliferation in a concentration-dependent manner (P＜0.05). Compared with the control group, the expression of key proteins in the mTORC1/4E-BP1 pathway and pyroptosis-related proteins was significantly increased in the model group (P＜0.05); compared with the model group, their expression was significantly decreased in the SSD-treated groups (P＜0.05). Compared with the control group, the mRNA expression of fibronectin, collagen I, IL-1β, and IL-18 was significantly increased in the model group (P＜0.05); compared with the model group, their expression was significantly decreased after SSD treatment (P＜0.05). Compared with the control group, LDH release was significantly increased in the model group (P＜0.05); compared with the model group, it was significantly decreased in the SSD-treated groups (P＜0.05). Immunofluorescence showed that the expression of Ki67 and vimentin was significantly increased in the model group compared with the control group (P＜0.05), and was significantly decreased after SSD treatment compared with the model group (P＜0.05). Conclusions SSD alleviates TGF-β1-induced pulmonary fibrosis by inhibiting pyroptosis, reducing fibrotic protein expression and suppressing inflammatory cytokine release.

Key words: saikosaponin D, pyroptosis, pulmonary fibrosis

中图分类号:

R285.5

闵锐, 李妲, 徐豫湘. 柴胡皂苷D抑制TGF-β1诱导的人胚肺成纤维细胞系HFL1纤维化相关蛋白的表达[J]. 基础医学与临床, 2026, 46(2): 241-249.

MIN Rui, LI Da, XU Yuxiang. Saikosaponin D inhibits TGF-β1-induced expression of fibrosis-related proteins in HFL1 human fetal lung fibroblasts[J]. Basic & Clinical Medicine, 2026, 46(2): 241-249.

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柴胡皂苷D抑制TGF-β1诱导的人胚肺成纤维细胞系HFL1纤维化相关蛋白的表达

Saikosaponin D inhibits TGF-β1-induced expression of fibrosis-related proteins in HFL1 human fetal lung fibroblasts

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