基于线粒体代谢与巨噬细胞极化的关系探讨回阳生肌方治疗慢性皮肤溃疡的效应机制

The restoring yang and promoting granulation method is applied to treat chronic skin ulcer by invigorating the spleen, invigorating the kidney, improving the Yang qi, and improving the image of the cold, and the restoring yang and promoting granulation method represented the internal control method. Continuous inflammation of chronic skin ulcer is an important factor affecting the healing process. In this process, macrophages are the key cells to regulate chronic inflammation of the skin.In chronic wounds, macrophages become significantly more m1-type, causing a persistent inflammatory response, while m2-type polarization decreases, leading to delayed wound healing. Macrophages under the external environment stimulation, mitochondria in glycolysis is extremely into M1, and mitochondrial oxidative phosphorylation is extremely into M2 type, the metabolic characteristics of mitochondria, which directly determines the phenotype of macrophage polarization. So the project adopts the systemic intervention, from the Angle of the mitochondrial metabolism and macrophage polarization, observe estoring yang and promoting granulation decoction to the influence of wound repair via mice model, and explore the effect mechanismof the treatment, so as to promote the importance of systemic intervention in chronic skin ulcer, and provide a scientific basis for the clinical application.

回阳生肌法，是健脾补肾、温补阳气，改善阴寒之象而治疗慢性皮肤溃疡的一种治法，回阳生肌方为内治法的代表方。慢性皮肤溃疡创面的持续炎症是影响愈合的重要因素，在这一过程中，巨噬细胞是调控皮肤慢性炎症愈合的关键细胞。慢性创面中，巨噬细胞极化为M1型显著增多，引起炎症反应持续存在，而M2型极化减少，导致创面愈合延迟。巨噬细胞在外界环境刺激下，线粒体进行糖酵解则极化为M1型，而线粒体进行氧化磷酸化则极化为M2型，这种线粒体的代谢特征，直接决定了巨噬细胞极化的表型。故本项目采用回阳生肌方进行全身干预，从线粒体代谢与巨噬细胞极化的角度，观察内服回阳生肌方对慢性伤口小鼠模型创面修复的影响，探讨回阳生肌方对慢性皮肤溃疡阴证的效应机制，提升全身干预在慢性皮肤溃疡中的重要性，为回阳生肌法的临床应用提供科学依据。

慢性皮肤溃疡创面迁延难愈，发病率升高，造成严重的经济和精神负担。回阳生肌法，是健脾补肾、温补阳气，改善阴寒之象而治疗慢性皮肤溃疡的一种治法，回阳生肌方为内治法的代表方。慢性皮肤溃疡创面的持续炎症是影响愈合的重要因素，在这一过程中，巨噬细胞是调控皮肤慢性炎症愈合的关键细胞。慢性创面中，巨噬细胞极化为M1型显著增多，引起炎症反应持续存在，而M2型极化减少，导致创面愈合延迟。巨噬细胞在外界环境刺激下，线粒体进行糖酵解则极化为M1型，而线粒体进行氧化磷酸化则极化为M2型，这种线粒体的代谢特征，直接决定了巨噬细胞极化的表型。故本项目采用回阳生肌方进行全身干预，通过糖尿病小鼠慢性皮肤创面，证实回阳生肌汤可上调骨髓、外周血、创面局部M2型巨噬细胞来促进创面愈合；通过体外实验，证实回阳生肌汤提取物可抑制LPS+IFN-γ诱导的RAW264.7巨噬细胞向M1型极化，促进向M2型极化，其通过激活STAT6信号通路发挥作用，并促进巨噬细胞线粒体能量代谢，明确回阳生肌方调节慢性皮肤溃疡巨噬细胞线粒体代谢和定向分化的作用，阐明中医“健脾补肾、回阳生肌”的效应机制，提升全身干预在慢性皮肤溃疡中的重要性，为回阳生肌法的临床应用提供科学依据。