中国临床医学2024，Vol.31Issue(5)：724-733,10.DOI:10.12025/j.issn.1008-6358.2024.20240828
乙醛脱氢酶2调控巨噬细胞M2型极化促进创面愈合
Aldehyde dehydrogenase 2 promotes wound healing by regulating M2 macrophage polarization
摘要
Abstract
Objective To verify the role of aldehyde dehydrogenase 2(ALDH2)in wound healing and to explore the underlying mechanisms.Methods A murine excisional wound model was developed and mice were randomly assigned to control group and Alda-1(ALDH2 agonist)group.Wound healing rate and activity of ALDH2 were measured.Masson staining was used to observe the collagen fiber content,and immunohistochemistry was used to detect the expression of ALDH2 and α-smooth muscle actin(α-SMA).The expression of collagen typeⅠandⅢ(Col-Ⅰ,Col-Ⅲ),and the number of F4/80,inducible nitric oxide synthase(iNOS)and CD206 positive(F4/80+,iNOS+,CD206+)cells were analyzed using immunofluorescences.Furthermore,interleukin(IL)-4-stimulated RAW264.7 cells were treated with Alda-1 or CVT-10216(an ALDH2 inhibitor)in vitro.The proportion of F4/80+CD206+cells were analyzed using flow cytometry.Anti-inflammatory and pro-inflammatory cytokines were examined using ELISA.The expression of protein associated with the AKT/mTOR pathway were detected via western blotting.Results Compared with control group,the wound healing rate of mice in the Alda-1 group was significantly improved,and the expression of Col-Ⅰ,Col-Ⅲ,and α-SMA in the wound surface increased.Although the number of F4/80+cells in wounds did not significantly differ,there was a decrease in iNOS+cells and an increase in CD206+cells.In vitro,compared to IL-4 group,IL-4+Alda-1 group exhibited an increased proportion of F4/80+CD206+macrophages and higher levels of anti-inflammatory factors,alongside a reduction in levels of pro-inflammatory factors.Conversely,IL-4+CVT-10216 group demonstrated a decreased proportion of F4/80+CD206+macrophages,lower levels of anti-inflammatory factors with a concomitant increase in pro-inflammatory factors.Additionally,the protein expressions of p-AKT and p-mTOR were significantly elevated in IL-4+Alda-1 group and diminished in IL-4+CVT-10216 group.Conclusion ALDH2 induces M2 macrophage polarization via AKT/mTOR pathway to promote wound healing in mice.关键词
创面愈合/巨噬细胞极化/乙醛脱氢酶2/Alda-1Key words
wound healing/macrophage polarization/aldehyde dehydrogenase 2/Alda-1分类
医药卫生引用本文复制引用
张思敏,亓发芝..乙醛脱氢酶2调控巨噬细胞M2型极化促进创面愈合[J].中国临床医学,2024,31(5):724-733,10.基金项目
国家自然科学基金(82172212).Supported by National Natural Science Foundation of China(82172212). （82172212）
