Oral Administration of Linoleic Acid Induces New Vessel Formation and Improves Skin Wound Healing in Diabetic Rats

Introduction
Impaired wound healing has been widely reported in diabetes. Linoleic acid (LA) accelerates the skin wound healing process in non-diabetic rats. However, LA has not been tested in diabetic animals.
Objectives
We investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats.
Methods
Dorsal wounds were induced in streptozotocin-induced type-1 diabetic rats treated or not with LA (0.22 g/kg b.w.) for 10 days. Wound closure was daily assessed for two weeks. Wound tissues were collected at specific time-points and used to measure fatty acid composition, and contents of cytokines, growth factors and eicosanoids. Histological and qPCR analyses were employed to examine the dynamics of cell migration during the healing process.
Results
LA reduced the wound area 14 days after wound induction. LA also increased the concentrations of cytokine-induced neutrophil chemotaxis (CINC-2αβ), tumor necrosis factor-α (TNF-α) and leukotriene B4 (LTB4), and reduced the expression of macrophage chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). These results together with the histological analysis, which showed accumulation of leukocytes in the wound early in the healing process, indicate that LA brought forward the inflammatory phase and improved wound healing in diabetic rats. Angiogenesis was induced by LA through elevation in tissue content of key mediators of this process: vascular-endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2).
Conclusions
Oral administration of LA hastened wound closure in diabetic rats by improving the inflammatory phase and angiogenesis.

引言
糖尿病患者的伤口愈合受损已被广泛报道。亚油酸（Linoleic acid, LA）可加速非糖尿病大鼠的皮肤伤口愈合进程，但目前尚未在糖尿病动物模型中开展相关试验。

研究目的
本研究旨在探究口服纯亚油酸是否能够改善链脲佐菌素（streptozotocin）诱导的糖尿病大鼠的伤口愈合情况。

实验方法
本研究对链脲佐菌素诱导的1型糖尿病大鼠构建背部伤口模型，将大鼠分为两组，分别给予或不给予0.22 g/kg体重的LA，干预时长为10天。在后续两周内每日评估伤口闭合情况。于特定时间点采集伤口组织样本，用于检测脂肪酸组成，以及细胞因子、生长因子与类花生酸类物质的含量。采用组织学分析及实时荧光定量聚合酶链式反应（qPCR），探究伤口愈合过程中细胞迁移的动态变化。

实验结果
伤口造模14天后，LA干预组的伤口面积显著缩小。同时，LA干预可升高细胞因子诱导的中性粒细胞趋化因子2αβ（CINC-2αβ）、肿瘤坏死因子-α（TNF-α）及白三烯B4（LTB4）的浓度，并下调巨噬细胞趋化蛋白-1（MCP-1）与巨噬细胞炎症蛋白-1（MIP-1）的表达水平。结合组织学分析结果（可见愈合早期伤口部位存在白细胞聚集），上述结果表明LA可提前启动炎症期，改善糖尿病大鼠的伤口愈合效果。此外，LA可通过升高伤口组织中血管生成关键介质——血管内皮生长因子（VEGF）与血管生成素-2（ANGPT-2）的含量，诱导血管生成。

研究结论
口服LA可通过改善炎症期进程并促进血管生成，加速糖尿病大鼠的伤口闭合。