中国组织工程研究2024，Vol.28Issue(29)：4620-4627,8.DOI:10.12307/2024.584
氧化苦参碱水凝胶通过激活角化细胞Nrf2/HO-1通路促进创面愈合
Oxymatrine hydrogel promotes wound healing by activating Nrf2/HO-1 pathway in keratinocytes
摘要
Abstract
BACKGROUND:Inflammation and oxidative stress contribute to the barriers of regeneration in chronic wound.Oxymatrine has various biological activities,such as anti-oxidation,anti-inflammation and so on,which may have the potential effect of promoting wound healing. OBJECTIVE:To investigate the effect of oxymatrine on wound healing and the protective effect on H2O2-induced oxidative stress injury in human keratinoid cell line HaCaT cells. METHODS:(1)In vivo experiment:Hyaluronic acid methacryloyl hydrogels containing 0,0.05,0.1,0.2 g/L oxymatrine were prepared.A full-layer skin defect model with a diameter of 12 mm was made in the back of 75 diabetic mice and randomly divided into five groups for intervention,with 15 mice in each group.The wounds of the model group were bandaged and fixed.The wounds of the hydrogel group were covered with hyaluronic acid methacryloyl hydrogel.The wounds of the low-dose,moderate-dose and high-dose oxymatrine groups were covered with hyaluronic acid methacryloyl hydrogel containing 0.05,0.1,and 0.2 g/L oxymatrine,respectively,and then bandaged and fixed after light curing.Relevant indicators were detected within 14 days.(2)In vitro experiment:Human keratinocyte line HaCaT was divided into five groups.The normal group was cultured conventionally.H2O2 group and low-,moderate-and high-concentration oxymatrine groups were treated with H2O2 for 4 hours,and then the medium was replaced with medium containing 0,0.05,0.1,and 0.2 g/L oxymatrine,respectively,and the relevant indexes were detected after 24 hours of culture. RESULTS AND CONCLUSION:(1)In vivo experiment:Compared with the model group,the wound healing rate of mice in the hydrogel group had no significant change.The wound healing rate of mice in the low-,moderate-and high-dose oxymatrine group was increased at 7 and 14 days after treatment(P<0.05).Pathological observation of wound section 14 days after treatment showed that compared with the model group,the thickness of regenerated epidermal layer,the number of microvessels,and collagen deposition in the moderate-and high-dose oxymatrine groups were increased(P<0.05).Western blot assay analysis of wound samples 7 days after surgery showed that compared with the model group,the protein expressions of tumor necrosis factor α and interleukin 6 in the moderate-and high-dose oxymatrine groups were decreased(P<0.05).(2)In vitro experiment:CCK8 assay,EdU and Ki67 staining showed that compared with the H2O2 group,the cell proliferation ability of the moderate-and high-concentration oxymatrine groups was significantly increased(P<0.05).Compared with the H2O2 group,mitochondrial membrane potential was increased(P<0.05)and reactive oxygen species content was decreased(P<0.05)in the moderate-and high-concentration oxymatrine groups.Western blot assay results showed that compared with the H2O2 group,the expression levels of Nrf2 nuclear protein,Nrf2 total protein,HO-1 protein,and superoxide dismutase 1 protein were increased in the high-concentration oxymatrine group(P<0.05).(3)These findings confirm that oxymatrine can alleviate oxidative stress damage in HaCat cells and accelerate wound healing by upregulating the levels of Nrf2 and HO-1 protein.关键词
氧化苦参碱/水凝胶/抗氧化/创面愈合/Nrf2/HO-1信号通路/HaCat细胞Key words
oxymatrine/hydrogel/antioxidant/wound healing/Nrf2/HO-1 signaling pathway/HaCat cell分类
医药卫生引用本文复制引用
刘璐,刘淑丹,刘晓丹,杨丽,凌晨,海小明,马会明,陈冬梅..氧化苦参碱水凝胶通过激活角化细胞Nrf2/HO-1通路促进创面愈合[J].中国组织工程研究,2024,28(29):4620-4627,8.基金项目
国家自然科学基金地区项目(81960355),项目负责人:陈冬梅 （81960355）
宁夏自治区自然科学基金项目(2022AAC03500),项目负责人:陈冬梅 （2022AAC03500）
宁夏回族自治区重点研发计划项目(2022BEG03147),项目负责人:刘淑丹 National Natural Science Foundation of China,No.81960355(to CDM) （2022BEG03147）
Natural Science Foundation of Ningxia Hui Autonomous Region,No.2022AAC03500(to CDM) （to CDM）
Key Research&Development Plan Project of Ningxia Hui Autonomous Region,No.2022BEG03147(to LSD) （to LSD）
