Dong Yunxian, Lv Dongming, Zhao Zirui, Xu Zhongye, Hu Zhicheng, Tang Bing
Department of Burn and Plastic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Front Bioeng Biotechnol. 2022 May 24;10:892015. doi: 10.3389/fbioe.2022.892015. eCollection 2022.
Hypertrophic scar (HS) is a fibrotic cutaneous disease with few effective therapies. Lycorine is a drug with pro-apoptotic ability and anti-fibrosis potential. This study aimed to test whether lycorine could trigger the apoptosis of hypertrophic scar fibroblasts (HSFs) to inhibit HS formation. The proapoptotic and anti-fibrosis effects of lycorine on the viability and apoptosis of human primary HSFs and their reactive oxygen species (ROS) production as well as a rabbit ear model of HS were determined by CCK-8, flow cytometry, Western blot, immunofluorescence, transwell migration, collagen gel contraction assays. Lycorine treatment selectively decreased the viability of HSFs, and induced their apoptosis, but not normal fibroblasts (NFs). Lycorine treatment increased the relative levels of Bax and cleaved PARP expression, cytochrome C cytoplasm translocation, but decreased Bcl-2, caspase-3 and caspase-9 expression, the mitochondrial membrane potential (MMP) in HSFs. Lycorine inhibited the migration and contraction of HSFs, and reduced the expression of collagen I, collagen III and α-SMA. Mechanistically, lycorine treatment stimulated high levels of ROS production, leading to apoptosis of HSFs while treatment with NAC, a ROS inhibitor, significantly mitigated or abrogated the pro-apoptotic and antifibrotic activity of lycorine in HSFs. Moreover, lycorine treatment mitigated the severity of HS in rabbit ears by inducing fibroblast apoptosis. These results indicate that lycorine has a potent anti-fibrotic activity and is a potential drug for intervention of HS.
肥厚性瘢痕（HS）是一种纤维化皮肤病，有效治疗方法较少。石蒜碱是一种具有促凋亡能力和抗纤维化潜力的药物。本研究旨在测试石蒜碱是否能触发肥厚性瘢痕成纤维细胞（HSFs）凋亡以抑制HS形成。通过CCK-8、流式细胞术、蛋白质免疫印迹、免疫荧光、Transwell迁移、胶原凝胶收缩试验，测定石蒜碱对人原代HSFs活力和凋亡的促凋亡及抗纤维化作用、其活性氧（ROS）生成以及HS兔耳模型的相关情况。石蒜碱处理选择性降低了HSFs的活力并诱导其凋亡，但对正常成纤维细胞（NFs）无此作用。石蒜碱处理增加了HSFs中Bax和裂解的PARP表达、细胞色素C的细胞质转位的相对水平，但降低了Bcl-2、半胱天冬酶-3和半胱天冬酶-9的表达以及线粒体膜电位（MMP）。石蒜碱抑制了HSFs的迁移和收缩，并降低了I型胶原、III型胶原和α-平滑肌肌动蛋白（α-SMA）的表达。机制上，石蒜碱处理刺激产生高水平的ROS，导致HSFs凋亡，而用ROS抑制剂NAC处理可显著减轻或消除石蒜碱对HSFs的促凋亡和抗纤维化活性。此外，石蒜碱处理通过诱导成纤维细胞凋亡减轻了兔耳HS的严重程度。这些结果表明石蒜碱具有强大的抗纤维化活性，是干预HS的一种潜在药物。
