[关键词]
[摘要]
研究了一种由小麦低聚肽、海洋鱼皮胶原低聚肽等组成的复合肽对小鼠全层皮肤缺损模型的愈合作用及其机制。成功构建小鼠全层皮肤缺损伤口模型后给予复合肽干预,在治疗后第4、14天,取小鼠背部皮肤分别进行HE染色观察伤口病理变化,CD34免疫荧光观察组织的血管生成情况。利用超高效液相色谱与质谱联用进行血清代谢组学检测,进行代谢轮廓分析和OPLS-DA分析和京都基因与基因组百科全书(KEGG)综合分析。在造成创伤后的第4、6、8天,复合肽组的伤口愈合率分别达到了为59%、74.1%、80.9%,明显超过模拟组;此外复合肽组的肉芽组织更加成熟,CD34阳性细胞的荧光数目也有所增长。在复合肽组中筛选出14个差异代谢物上调,20个差异代谢物下调;KEGG分析显示复合肽组在牛磺酸和次牛磺酸代谢、精氨酸和脯氨酸代谢、初级胆汁酸生物合成等6条通路中显著富集。该复合肽可以显著缩短小鼠全厚皮肤缺损伤口的修复时间,可能是通过促进毛细血管生成,促进蛋白的合成来加速伤口愈合。
[Key word]
[Abstract]
A mouse full-thickness skin defect model was established to analyze the healing effect of a composite peptide comprising wheat oligopeptide and marine fish skin collagen oligopeptide. On the 4th and 14th days after the intervention, pathological changes in the wound were assessed by subjecting the skin taken from the back of mice to H&E staining; the extent of angiogenesis was determined based on CD34 expression (estimated by immunofluorescence). Serum metabolomic profiles were obtained using ultra-high-performance liquid chromatography and mass spectrometry to screen for differential metabolites whose expression was significantly altered. Metabolic profile analysis, OPLS-DA analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. On the 4th, 6th, and 8th days after the injury, the wound healing rates in the composite-peptide group reached 59%, 74.1%, and 80.9% respectively, which were significantly higher than those observed in the model group. Furthermore, the granulation tissue continued to mature, and higher counts of CD34-positive cells were observed in the composite-peptide group. Metabolomic analysis showed that among differentially expressed metabolites in the composite-peptide group, 14 were upregulated and 20 were downregulated. KEGG pathway analysis showed that the composite peptides were significantly enriched for six pathways, i.e., taurine and hypotaurine metabolism, arginine and proline metabolism, and primary bile acid biosynthesis (compared to the model group). Thus, composite peptides can reduce the repair time of full-thickness skin defects in mice, possibly by promoting capillary formation and protein biosynthesis to accelerate wound healing.
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[基金项目]
南昌市高层次科技创新人才“双百计划”(批准号:〔2022〕321)