Yue Han, Zhang Xiaoling, Zhao Zhiyi, Gong Song, Shao Shiying
Division of Endocrinology, Tongji Hospital, Huazhong University of Science & Technology, Wuhan, 430030, PR China; Branch of National Clinical Research Center for Metabolic Diseases, Hubei, PR China.
Division of Endocrinology, Tongji Hospital, Huazhong University of Science & Technology, Wuhan, 430030, PR China; Branch of National Clinical Research Center for Metabolic Diseases, Hubei, PR China.
Int Immunopharmacol. 2025 Feb 6;147:114050. doi: 10.1016/j.intimp.2025.114050. Epub 2025 Jan 10.
Recent studies demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RA) have promising prospects in promoting wound healing. In this study, we intend to investigate the pro-healing effect and potential molecular mechanism of topical administration of GLP-1RA liraglutide on wounds in normoglycemic mice. Two full-thickness wounds were created on the back of the C57BL/6 mice. The "lower" wounds were topically infiltrated with liraglutide every day after injury; while the "upper" wounds were infiltrated with saline solution. Wound area was measured daily during the 10-day study period. The wound tissue was stained with H&E and immunofluorescence. Western blotting was performed to detect the markers in macrophages. The results showed that topical administration of liraglutide resulted in a rapid reduction of wound size. The capillary density and the expression of vascular endothelial growth factor (VEGF)-A were significantly increased in liraglutide-treated wounds. Findings from immunofluorescence and Western blotting revealed that liraglutide promoted phenotypic polarization of macrophages from M1 to M2. We further identified that M2a macrophages predominantly presented in the early and middle stages of inflammation phase and M2d macrophages presented in the middle and late stages. Our study suggested that GLP-1RA liraglutide could promote wound healing in normoglycemic mice, which is partly attributed to the modulation of the macrophage polarization from M1 subtype to M2 subtype.
近期研究表明，胰高血糖素样肽-1受体激动剂（GLP-1RA）在促进伤口愈合方面具有广阔前景。在本研究中，我们旨在探讨局部应用GLP-1RA利拉鲁肽对正常血糖小鼠伤口的促愈合作用及潜在分子机制。在C57BL/6小鼠背部制造两个全层伤口。“下方”伤口在受伤后每天局部注射利拉鲁肽；而“上方”伤口注射盐溶液。在为期10天的研究期间每天测量伤口面积。对伤口组织进行苏木精-伊红染色和免疫荧光染色。进行蛋白质免疫印迹法检测巨噬细胞中的标志物。结果显示，局部应用利拉鲁肽可使伤口大小迅速减小。利拉鲁肽处理的伤口中毛细血管密度和血管内皮生长因子（VEGF）-A的表达显著增加。免疫荧光和蛋白质免疫印迹法的结果表明，利拉鲁肽可促进巨噬细胞从M1型向M2型的表型极化。我们进一步确定，M2a巨噬细胞主要出现在炎症期的早期和中期，M2d巨噬细胞出现在中期和后期。我们的研究表明，GLP-1RA利拉鲁肽可促进正常血糖小鼠的伤口愈合，这部分归因于其对巨噬细胞从M1亚型向M2亚型极化的调节作用。
