中国药物警戒 ›› 2026, Vol. 23 ›› Issue (7): 775-782.
DOI: 10.19803/j.1672-8629.20250922

• 基础与临床研究 • 上一篇    下一篇

黑布药膏对缺氧状态下瘢痕疙瘩成纤维细胞生长及线粒体凋亡的影响

马卉1, 李林昌2, 张天蕾1, 陈维文1,*, 郑海云3#   

  1. 1首都医科大学附属北京中医医院皮肤科,北京 100010;
    2北京市东城区东花市社区卫生服务中心,北京 100010;
    3中国中医科学院中医药科技合作中心,北京 100700
  • 收稿日期:2025-12-19 出版日期:2026-07-15 发布日期:2026-07-16
  • 通讯作者: #为共同通信作者。*陈维文,男,博士,主任医师,瘢痕疙瘩中西医治疗与机制研究。E-mail: chenweiwen@bjzhongyi.com
  • 作者简介:马卉,女,博士,主治医师,瘢痕疙瘩中西医治疗与机制研究。
  • 基金资助:
    国家自然科学基资助项目（82305247）

Effects of Heibu Ointment on the growth and mitochondrial apoptosis of keloid fibroblasts under hypoxia

Ma Hui1, Li Linchang2, Zhang Tianlei1, Chen Weiwen1,*, Zheng Haiyun3#   

  1. 1Department of Dermatology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China;
    2Donghua Market Community Health Service Center, Beijing 100010, China;
    3Science and Technology Collaborating Center for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
  • Received:2025-12-19 Online:2026-07-15 Published:2026-07-16

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摘要： 目的 探讨黑布药膏对缺氧状态下瘢痕疙瘩成纤维细胞（Keloid Fibroblasts,KFs）增殖、迁移、凋亡、缺氧诱导因子-1α（Hypoxia-Inducible Factor-1α,HIF-1α）及线粒体凋亡途径相关蛋白表达的影响。方法 利用人KFs细胞株进行细胞培养,将KFs分为常氧组,缺氧组,缺氧+黑布药膏提取物组（500、250、125、62.5、31.25 μg·mL-1）,每组培养24 h后,采用MTT实验检测KFs增殖情况并挑选后续实验干预浓度。然后将KFs分为常氧组、常氧+黑布药膏提取物组（125 μg·mL-1）、缺氧组、缺氧+黑布药膏提取物组（125 μg·mL-1）,利用MTT实验、流式细胞术、细胞划痕实验、免疫荧光及Western-Blot法检测黑布药膏提取物对缺氧状态下KFs增殖、凋亡、迁移、HIF-1α表达及线粒体凋亡途径相关蛋白（Bax、Bcl-2、Caspase-3）表达水平的影响。结果 与常氧条件相比,缺氧可显著增强KFs增殖能力（P<0.01）、抑制细胞凋亡（P<0.01）并促进其迁移（P<0.01）,同时上调HIF-1α荧光强度及蛋白表达（P<0.01）;在线粒体凋亡途径中,缺氧组Bax与Caspase-3表达降低（P<0.01）,而Bcl-2表达升高（P<0.01）。给予黑布药膏提取物干预后,与单纯缺氧组相比,KFs增殖受到抑制（P<0.01）、凋亡率提高（P<0.01）、迁移能力减弱（P<0.01）;同时,HIF-1α荧光强度与蛋白表达均下降（P<0.01）,且Bax、Caspase-3表达升高,Bcl-2表达降低（P<0.01）。结论 黑布药膏提取物可抑制缺氧状态下KFs增殖及迁移,诱导其凋亡,同时降低HIF-1α水平,激活线粒体凋亡途径,从而发挥消瘢作用。

关键词: 黑布药膏, 瘢痕疙瘩, 人瘢痕疙瘩成纤维细胞（KFs）株, 缺氧, 成纤维细胞, 线粒体凋亡

Abstract: Objective To investigate the effects of Heibu ointment on the proliferation, migration, apoptosis and expressions of hypoxia-inducible factor-1α (HIF-1α), and key proteins of the mitochondrial apoptotic pathway in keloid fibroblasts (KFs) under hypoxic conditions. Methods A human KFs cell line was cultured and divided into the following groups: normoxia, hypoxia, and hypoxia treated with Heibu ointment at concentrations of 500, 250, 125, 62.5, and 31.25 μg·mL-1. After 24 hours of culture, the MTT assay was performed to evaluate the proliferation of KFs and to select the optimal concentration for subsequent experiments. The KFs were then regrouped into normoxia, normoxia + 125 μg·mL-1 extract, hypoxia, and hypoxia + 125 μg·mL-1 extract. MTT assay, flow cytometry, scratch wound assay, immunofluorescence, and Western blot were used to evaluate the effects of the extract on the proliferation, apoptosis, migration and HIF-1α expression of KFs, and on the protein levels of key mitochondrial apoptosis factors (Bax, Bcl-2, Caspase-3). Results Compared with normoxic conditions, hypoxia significantly enhanced KFs’ proliferation (P<0.01), suppressed apoptosis (P<0.01), and promoted cell migration (P<0.01) while upregulating both the fluorescence intensity and protein expression of HIF-1α (P<0.01). Within the mitochondrial apoptotic pathway, hypoxia downregulated the expression levels of Bax and Caspase-3 (P<0.01) while upregulating Bcl-2 expressions (P<0.01). Treatment with Heibu ointment inhibited KFs’ proliferation (P<0.01), increased the apoptosis rate (P<0.01), and reduced migratory capacity P<0.01) compared to the hypoxia alone group. Concurrently, this ointment decreased both HIF-1α fluorescence intensity and protein expressions (P<0.01), elevated the expression levels of Bax and Caspase-3, but lowered Bcl-2 expression (P<0.01). Conclusion Our findings indicate that Heibu ointment can exert anti-scarring effects by inhibiting proliferation/migration, inducing apoptosis, downregulating HIF-1α, and activating the mitochondrial apoptotic pathway in hypoxic KFs.

Key words: Heibu Ointment, Keloid, Human Keloid Fibroblasts (KFs) Line, Hypoxia, Fibroblasts, Mitochondrial Apoptosis

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