牛骨胶原低聚肽通过调控PI3K/AKT/mTOR信号通路促进术后伤口愈合的作用及机制研究

Poor wound healing is common symptoms after surgery, the incidence of which is 7%. Recent studies have found that the PI3K/Akt/mTOR signaling pathway, which is susceptible to nutritional signals, plays an important role in wound healing. Oligopeptides of bovine bone collagen are a kind of small molecular biological active peptides, which can effectively supplement the enteral nutrition, improve the body immunity, and have the potential of promoting wound healing. In our previous studies, we found that Oligopeptides of bovine bone collagen enhanced the tensile strength of skin, reduced the remaining area of the wound, and had beneficial effects on the wound healing after surgery in mice. However, the possible mechanism is still unknown. The present study was divided into two parts including human experiment and cell experiment. Primarily, we evaluate the effects of oligopeptides of bovine bone collagen on postoperative wound healing in patients with gastrointestinal surgery. Next, we observe the effects of oligopeptides of bovine bone collagen on fibroblasts which are the main cells repairing the wound. The aim of the present study is to evaluate the effect of oligopeptides of bovine bone collagen on wound healing and the possible mechanism of the PI3K/AKT/mTOR signaling pathway. The present study is to provide important scientific evidence for promoting the clinical nutritional support in the process of postoperative wound healing.

伤口愈合不良是外科手术后常见的并发症之一，发生率达7%。最新的研究发现PI3K/Akt/mTOR信号通路在伤口愈合过程中发挥着重要作用，且其容易受到营养信号的影响。牛骨胶原低聚肽是一种小分子生物活性肽，可以有效的补充肠内营养，提高机体免疫力，具有促进伤口愈合的潜力。课题组前期研究结果发现牛骨胶原低聚肽可增强小鼠皮肤抗张力强度，缩小伤口剩余面积，具有良好的促进术后伤口愈合的作用，但其具体机制尚不清楚。本项目拟采用人群实验和细胞实验相结合的方法，首先探讨牛骨胶原低聚肽对胃肠道手术患者术后伤口愈合的干预效果，其次观察牛骨胶原低聚肽对伤口愈合的主要修复细胞—成纤维细胞功能的影响，以综合评价牛骨胶原低聚肽对术后伤口愈合的促进作用和以PI3K/AKT/mTOR信号通路为靶点的作用机制。本项目的顺利开展将为术后临床营养支持和伤口愈合不良的防治提供重要科学依据。

伤口愈合不良是外科手术后常见的并发症之一，发生率达7%。课题组前期研究结果发现牛骨胶原低聚肽可增强小鼠皮肤抗张力强度，缩小伤口剩余面积，具有良好的促进术后伤口愈合的作用，但其具体机制尚不清楚。本项目通过临床手术人群试验观察牛骨胶原低聚肽对术后患者伤口愈合情况、营养学指标、炎症因子的干预效果，同时通过细胞实验观察其对成纤维细胞的细胞增殖和迁移、氧化应激、炎症因子、胶原代谢及PI3K/AKT/mTOR信号通路的影响。人群试验结果发现牛骨胶原低聚肽可以有效提高术后患者前白蛋白水平，降低炎症水平，提升术后伤口甲级愈合率。细胞试验发现牛骨胶原低聚肽可以有效提高成纤维细胞活性，减少细胞凋亡；划痕实验结果显示牛骨胶原低聚肽可以有效促进成纤维细胞迁移；同时牛骨胶原低聚肽可提高细胞上清液中羟脯氨酸浓度和细胞中转化生长因子-β（TGF-β）表达水平，从而发挥其调节胶原代谢的作用；牛骨胶原低聚肽还可有效抑制炎症因子ICAM-1的蛋白表达，提高超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性，降低丙二醛（MDA）含量；另外，牛骨胶原低聚肽可以有效激活成纤维细胞中PI3K/AKT/mTOR信号传导通路。本项目研究结果为牛骨胶原低聚肽作为一种安全有效的促伤口愈合的食源性营养制剂提供了实验依据，也为术后临床营养支持和伤口愈合不良的防治提供一定的理论依据。