白色脂肪棕色化下调琥珀酸通过巨噬细胞极化的炎症调控促进糖尿病创面愈合的机制研究

糖尿病创面是慢性创面治疗的难点，其难以愈合的机制尚未明确。课题组前期研究发现：正常创面修复过程中存在皮下白色脂肪棕色化的现象，而糖尿病创面白色脂肪棕色化的过程受损，使用棕色化特异性的药物诱导，可显著促进糖尿病创面的愈合。随后的基因及代谢组学的研究发现：相较于普通创面，糖尿病创面存在琥珀酸代谢产物的异常聚集。据此我们推测：糖尿病创面局部高聚集的琥珀酸在白色脂肪被棕色化诱导后可被显著地下调，随后调节巨噬细胞的M2型极化可逆转创面持续性的慢性炎症水平，从而促进创面愈合。本研究拟采用细胞生物学技术、蛋白生化技术、代谢分子检测技术、病理检测等技术，研究白色脂肪棕色化诱导在糖尿病创面愈合中的作用机制，并探讨针对性诱导创面周围脂肪棕色化或下调局部琥珀酸浓度以治疗糖尿病创面的可行性及相关机制，为从代谢水平改善糖尿病创面的治疗提供新的思路。

Diabetic wound is one of the most difficultly treated chronic wounds and the mechanism of its delayed healing remain unclear. Our previous study found an interesting phenomenon that subcutaneous white fat would undergo browning during the process of normal wound repair, while it did not undergo browning in the diabetic wound. Medical induction of subcutaneous white fat browning in the diabetic wound can significantly promote the healing of it. The gene array and metabonomics analysis showed that there was an increasing accumulation of succinate in diabetic wounds compared with normal wounds. Therefore, we speculated that the high concentration ofsuccinate in normal wounds can be consumed by the browning adipose tissue, which drives local macrophages towards M2 polarization and reverses the chronic inflammation in wounds, while diabetic wounds fail. In this study, cell biology, protein biochemistry, metabonomics and pathological technology were used to study the role of white adipose tissue browning induction in diabetic wound healing, and to explore the feasibility and related mechanism of targeted induction of adipose tissue browning around the wound or down-regulation of local succinate concentration for the treatment of diabetic wound, aiming to provide new solutions for the treatment of diabetic wounds.