目的 探究皮肤再生医疗技术（Moist exposed burn therapy/Moist exposed burn ointment，MEBT/MEBO）联合壮医解毒祛邪法通过调控Wnt/β-catenin、Hippo/YAP信号通路与血浆代谢产物间的交互效应促进慢性难愈合创面修复的机制。方法 SPF级SD雄性大鼠100只随机分为空白对照组、模型组、外治组、壮药组、联合组，每组20只。空白对照组仅建立全层皮肤缺损开放性创面，其余各组建立慢性难愈合创面模型。空白对照组、模型组正常饲养，外治组按皮肤再生医疗技术换药每日1次，壮药组使用壮药水煎剂溶液灌胃每日1次，联合组同时使用皮肤再生医疗技术换药及壮药水煎剂溶液灌胃每日1次。连续干预12天，在第1、4、8、12天取创面皮肤组织进行实时荧光定量PCR检测β-catenin、YAP1、MST1、Cyclin D1、Survivin的表达情况。在第12天取动脉血进行气相色谱-质谱检测。结果 经12天治疗后，联合组创面明显缩小，有效率优于模型组、外治组、壮药组（P<0.005）。各组大鼠β-catenin、YAP1、Cyclin D1、Survivin的表达随时间递推而增大，MST1的表达随时间递推而减小，差异均有统计学意义（P<0.05），其中联合组在调控各mRNA的表达方面均优于模型组、外治组、壮药组（P<0.05）。气相色谱-质谱检测结果显示各组大鼠血浆代谢产物均有不同程度的改善，其中联合组血浆代谢产物改善情况明显优于模型组、外治组、壮药组。结论 MEBT/MEBO联合壮医解毒祛邪法能通过调控Wnt/β-catenin、Hippo/YAP信号通路与血浆代谢产物间的交互效应，影响血管内皮细胞功能，更好地促进慢性难愈合创面修复。

Objective To explore the mechanism of MEBT/MEBO combined with Zhuang medicine detoxification to promote the healing of chronic refractory wounds by regulating the interaction between Wnt/β-catenin, Hippo/YAP signaling pathway and plasma metabolites.Methods 100 SPF male SD rats were randomly divided into blank control group, model group, external therapy group, Zhuang medicine group, combined group, with 20 rats in each group. The blank control group only established full-thickness skin defect open wound model, the other groups established chronic refractory wound model. Blank control group and model group were fed normally, external therapy group was given MEBT/MEBO dressing change once a day, Zhuang medicine group was given Zhuang decoction solution once a day, combined group was given MEBT/MEBO and Zhuang decoction solution once a day. The expression of β-catenin, YAP1, MST1, Cyclin D1 and Survivin was detected by RT-PCR at 1 d, 4 d, 8 d and 12 d after continuous intervention for 12 days. Arterial blood was collected on 12 d for GC-MS detection.Results After 12 days of intervention, the wound surface of the combined group was significantly reduced, and the effective rate was better than that of model group, external therapy group and Zhuang medicine group (P<0.005). The expression of β-catenin, YAP1, Cyclin D1 and Survivin increased recursively with time, while the expression of MST1 decreased recursively with time, with statistical significance (P<0.05). The combined group was superior to model group, external therapy group and Zhuang medicine group in regulating mRNA expression (P<0.05). The results of GC-MS showed that the plasma metabolites in each group were improved to varying degrees, and the improvement of plasma metabolites in combined group was significantly better than that in model group, external therapy group and Zhuang medicine group.Conclusion MEBT/MEBO combined with Zhuang medicine detoxification can affect the function of vascular endothelial cells by regulating the interaction between Wnt/β-catenin, Hippo/YAP signaling pathways and plasma metabolites, and better promote the repair of chronic refractory wounds.

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广西壮族自治区科技厅广西自然科学基金青年科学基金（2018GXNSFBA050018）：MEBT/MEBO联合壮医解毒祛邪法探究Wnt和Hippo通路的交互作用促进慢性难愈合创面修复的机制，负责人：何晓微；国家科学技术部重大项目（2017YFC1703903）：蒙、壮、朝、畲名老民族医药学术传承研究，负责人：哈斯巴根。