Qian Huan, Zhang Lei, Wang Chen, Zhang Mengwen, Wen Li, Zhao Wenxia
Department of Plastic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Nursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Int Immunopharmacol. 2025 Feb 20;148:114181. doi: 10.1016/j.intimp.2025.114181. Epub 2025 Jan 28.
Keloids are abnormal scars formed due to fibroblast dysfunction and excessively deposited extracellular matrix (ECM). Despite the unclear process leading to the occurrence of keloids, several studies have demonstrated that histamine and its H1 receptor can effectively regulate fibroblast functions, contributing to keloid formation. Chlorpheniramine maleate (CPM) as a first-generation H1 antihistamine has been widely applied in symptomatic treatment of allergic conditions but its effects on keloids are unknown. This study holds the objective of exploring its effect on keloids. Cell Counting Kit-8 (CCK-8), apoptosis, cell cycle and migration assays were conducted to determine the effects of CPM on human keloid fibroblasts (KFs), with its therapeutic effect evaluated by constructing a keloid model in nude mice. RNA sequencing analysis, ELISA, western blotting and immunohistochemistry assisted in examining the anti-keloid mechanism of CPM. It was observed that CPM inhibited the proliferation and migration of KFs, promoted apoptosis of KFs, and blocked the G0/G1 phase of KFs. Moreover, local intralesional injection of CPM into nude mice keloid model significantly reduced keloid scars. According to RNA sequencing analysis, the gene expression of IL-6 and JAK-STAT signaling pathway were both negatively related in CPM group versus the control group. According to the in vivo and vitro experiment results, the anti-keloid activity of CPM was attributed to its inhibitory effect on the IL-6/JAK1/STAT3 signal pathway. In summary, CPM holds great potential for localized treatment of keloids.
瘢痕疙瘩是由于成纤维细胞功能障碍和细胞外基质（ECM）过度沉积而形成的异常瘢痕。尽管导致瘢痕疙瘩发生的过程尚不清楚，但多项研究表明，组胺及其H1受体可有效调节成纤维细胞功能，促进瘢痕疙瘩的形成。马来酸氯苯那敏（CPM）作为第一代H1抗组胺药已广泛应用于过敏性疾病的对症治疗，但其对瘢痕疙瘩的影响尚不清楚。本研究旨在探讨其对瘢痕疙瘩的影响。采用细胞计数试剂盒-8（CCK-8）、凋亡、细胞周期和迁移实验来确定CPM对人瘢痕疙瘩成纤维细胞（KFs）的影响，并通过在裸鼠中构建瘢痕疙瘩模型来评估其治疗效果。RNA测序分析、酶联免疫吸附测定（ELISA）、蛋白质免疫印迹法和免疫组织化学辅助检测CPM的抗瘢痕疙瘩机制。结果发现，CPM抑制KFs的增殖和迁移，促进KFs的凋亡，并阻断KFs的G0/G1期。此外，向裸鼠瘢痕疙瘩模型局部病灶内注射CPM可显著减少瘢痕疙瘩。根据RNA测序分析，CPM组与对照组相比，白细胞介素-6（IL-6）的基因表达和JAK-STAT信号通路均呈负相关。根据体内和体外实验结果，CPM的抗瘢痕疙瘩活性归因于其对IL-6/JAK1/STAT3信号通路的抑制作用。综上所述，CPM在瘢痕疙瘩的局部治疗方面具有巨大潜力。
