基因组信息指导下仿刺参来源具有修复功能的活性肽的挖掘及活性评价

doi:10.3976/j.issn.1002-4026.20260052

摘要/Abstract

摘要： 伤口愈合是组织损伤后实现功能修复与恢复的关键生理过程，其核心涉及损伤所启动的一系列复杂生物学机制。受个体身体状况、创伤的面积大小与严重程度，以及是否并发感染等多种因素的影响，多数情况下伤口修复需要借助医疗手段进行干预。特别是慢性伤口的愈合过程，往往难以获得理想的治疗效果，所以会导致社会经济与医疗体系负担变得更加严重。与传统的药物相比，天然生物活性肽具有低副作用、低免疫性、低毒性、良好的生理功能、细胞通透性和生物多样性等特点，展现出了新一代愈合药物的潜力。作为开展创面愈合与组织再生研究的重要生物，海参具有极强再生特性，是开展伤口愈合与组织再生研究的重要模式生物。本研究以糙刺参（Stichopus horrens）来源的生长因子Sh-EGFl-1为探针，在仿刺参（Apostichopus japonicus）基因组中，借助Local Blast比对技术筛选获得1条同源序列DE37，然后通过化学合成的方式制备得到多肽。圆二色谱检测结果显示，DE37的二级结构占比例分别为：α螺旋3.7%、β折叠41.1%、转角21.5%、无规则卷曲33.6%。细胞实验结果显示，50 μmol/L 的 DE37 能有效推动 HaCaT 细胞的增殖与迁移；5 μmol/L 与 10 μmol/L 浓度的 DE37 均能够显著促进 L929 细胞的增殖及迁移过程，其中以 10 μmol/L 浓度组的促进作用最为显著，可显著促进 L929 细胞增殖，使其增殖率提高 39.39%；同时能加速细胞迁移，划痕愈合率提升 26.97%。进一步通过分子对接，推测了活性肽DE37与受体EGFR的结合口袋和关键氨基酸残基。

关键词: 防刺参, 活性肽, 细胞增殖, 细胞迁移, 分子对接

Abstract: Wound healing is a key physiological process for functional repair and recovery following tissue injury, involving a series of complex biological mechanisms initiated by damage. Affected by multiple factors such as the individual’s physical condition, wound size and severity, and the presence of concurrent infection, wound repair often requires medical intervention. In particular, the healing process of chronic wounds often fails to achieve ideal therapeutic outcomes, thereby placing an increasingly heavy burden on the socioeconomic systems and healthcare services. Compared with conventional drugs, natural bioactive peptides exhibit advantages such as low side effects, low immunogenicity, low toxicity, favorable physiological functions, good cell permeability, and high biodiversity, demonstrating great potential as next-generation healing agents. As an important organism for research on wound healing and tissue regeneration, sea cucumbers possess remarkable regenerative capabilities and serve as a valuable model organism for related studies. In this study, the growth factor Sh‑EGFl‑1 derived from Stichopus horrens was used as a probe to screen the genome of Apostichopus japonicus. A homologous sequence, DE37, was identified through local BLAST alignment and subsequently synthesized chemically. Circular dichroism spectroscopy revealed that the secondary structure of DE37 consisted of 3.7% α-helix, 41.1% β-sheet, 21.5% β-turn, and 33.6% random coil. Cell experiments showed that 50 µmol/L DE37 effectively promoted the proliferation and migration of HaCaT cells. DE37 at 5 µmol/L and 10 µmol/L significantly enhanced the proliferation and migration of L929 cells, with the 10 μmol/L group showing the most pronounced effect, increasing the proliferation rate by 39.39%. In addition, it accelerated cell migration, improving the wound healing rate by 26.97%. Further molecular docking was performed to predict the binding pocket and key amino acid residues involved in the interaction between the active peptide DE37 and the receptor EGFR.

Key words: Apostichopus japonicus, bioactive peptides, cell proliferation, cell migration, molecular docking

中图分类号:

Q516

陈鑫华, 王伟涛, 殷欣, 张立新, 孟艺伟, 夏雪奎. 基因组信息指导下仿刺参来源具有修复功能的活性肽的挖掘及活性评价[J]. 山东科学, 0, (): 1-.

CHEN Xinhua, WANG Weitao, YIN Xin, ZHANG Lixin, MENG Yiwei, XIA Xuekui. Genome-guided discovery and bioactivity evaluation of repair-promoting peptides from Apostichopus japonicus[J]. Shandong Science, 0, (): 1-.

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