关键词: 慢性烧伤创面, 脂质体凝胶, 油酸, 创面愈合, 炎症反应, 氧化应激, 细胞增殖

Abstract: BACKGROUND: Oleic acid can regulate inflammation and immune responses, and has the potential to repair skin wounds. Oleic acid has a short retention time at the lesion. It is prone to self oxidation and deterioration in the air, and suitable drug carriers are needed to fully exert the therapeutic effect of oleic acid. 
OBJECTIVE: To investigate the efficacy of oleic acid-liposome gel in the treatment of chronic burn wounds.  
METHODS: Oleic acid liposome solution was prepared by thin film dispersion method, and then dissolved in Poloxamer gel matrix to prepare oleic acid-liposome gel. (1) In vitro experiment: Oleic acid-liposome gel solution was prepared by adding different volumes of oleic acid-liposome gel into cell medium (volume ratio: 1:3, 1:9, 1:27, respectively). Alma-blue reagent was used to detect the effects of different concentrations of oleic acid-liposome gel on the proliferation of human keratinocytes and human fibroblasts. Crystal violet staining was used to observe cell morphology. (2) In vivo experiment: The animal model of chronic burn wounds was established by using full-thickness burn of SD rat back skin combined with local subcutaneous injection of epirubicin. The 30 successfully modeled rats were randomly divided into five groups with six rats in each group. The wounds of oleic acid liposome gel group, oleic acid group, liposome gel group, positive control group and negative control group were applied with gauze of oleic acid liposome gel, oleic acid, liposome gel, recombinant human epidermal growth factor gel and normal saline. The dressing was changed once every other day. A total of 16 doses were administered. The wound healing was observed.
RESULTS AND CONCLUSION: (1) In vitro experiments: Alma-blue reagent detection and crystal violet staining showed that oleic acid liposome gel solution with volume ratio of 1:9 could promote the proliferation of human keratinocytes and human fibroblasts. (2) In vivo experiment: The wound healing time of the oleic acid liposome gel group was shorter than that of the other four groups (P < 0.01), and the wound healing rate at 4, 8, 12, 16, and 20 days was higher than that of the other four groups (P < 0.01). After administration, hematoxylin-eosin staining showed epithelialization and healing of wounds in all five groups, and the epidermal thickness of oleic acid liposome gel group was the closest to normal skin and better than the other four groups. Immunohistochemical staining showed that the expressions of cytokeratin 10, tumor protein 63, α-smooth muscle actin, collagen I, tumor necrosis factor α, interleukin 6, malonaldehyde, and superoxide dismutase in oleic acid liposome gel group were closest to those in normal skin, and superior to those in other four groups. On days 12 and 32 of administration, the expressions of tumor necrosis factor α, interleukin 6, malondialdehyde, and superoxide dismutase in wound homogenate supernatant in oleic acid liposome gel group were closest to those in normal skin, and superior to those in other four groups. (3) The results showed that oleic acid liposome gel could promote the proliferation of keratinocytes and fibroblasts, reduce inflammation and oxidative stress injury, and promote the healing of chronic burn wounds. 

Key words: chronic burn wound, liposome gel, oleic acid, wound healing, inflammatory reaction, oxidative stress, cell proliferation