[关键词]
[摘要]
目的 探讨肉桂酸对糖尿病小鼠创面愈合及创口修复细胞迁移的影响。方法 将16只雄性db/db小鼠随机分为模型组和肉桂酸(10 mg/kg)组,建立切除性创面夹板模型,另取6只C57BL/6J小鼠作为对照组。连续给药16 d,每2天观察创面愈合程度;给药结束后对皮肤组织进行病理组织学和免疫荧光染色,检测小鼠创面愈合与组织形态学变化和创面血管密度。根据创面愈合的过程,采用不同细胞系进行体外实验。qRT-PCR检测肉桂酸对巨噬细胞炎症因子表达的影响;Matrigel基质胶成管法、划痕实验、qRT-PCR检测肉桂酸对创口修复细胞包括人脐静脉内皮细胞、小鼠成纤维细胞和人角质形成细胞的成管能力、迁移能力、分化能力的影响。结果 给药16 d后,肉桂酸显著加快糖尿病小鼠伤口愈合速度,提高体内微血管密度和创面周围再上皮化率及肉芽组织厚度。肉桂酸可显著降低巨噬细胞炎症因子表达,提高创口修复细胞的迁移能力。结论 肉桂酸通过抑制过度炎症反应,促进创口修复细胞迁移,促进血管生成和胶原沉积,加速糖尿病小鼠创面愈合。
[Key word]
[Abstract]
Objective To investigate the effect of cinnamic acid on wound healing and wound repair cell migration in diabetic mice. Methods A total of 16 male db/db mice were randomly divided into model group and cinnamic acid (10 mg/kg) group, an excisional wound splint model was established, and six C57BL/6J mice were taken as control group. Drugs were continuously administration for 16 d, the degree of wound healing was observed every two days; After administration, histopathology and immunofluorescence staining were performed on skin tissue to detect wound healing, tissue morphological changes and wound vascular density in mice. According to the process of wound healing, different cell lines were used for in vitro experiments. qRT-PCR was used to detect the effect of cinnamic acid on the expression of inflammatory factors in macrophages; Matrix gel tube formation method, scratch assay, qRT-PCR were used to detect the effect of cinnamic acid on tube-forming, migration and differentiation abilities of wound repair cells including human umbilical vein endothelial cells, mouse fibroblasts and human keratinocytes. Results After 16 d of administration, cinnamic acid significantly accelerated wound healing in diabetes mice, increased microvessel density, periwound re-epithelialisation rate and granulation tissue thickness in vivo. Cinnamic acid could significantly reduce the expression of inflammatory factors in macrophages and improve the migration ability of wound repair cells. Conclusion Cinnamic acid can accelerate wound healing in diabetes mice by inhibiting excessive inflammatory reaction, promoting migration of wound repair cells, promoting angiogenesis and collagen deposition.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金资助项目(82174205);国家自然科学基金资助项目(82274135);天津市教委科研计划项目(2021ZD026)