【目的】 基于核因子E2相关因子2（Nrf2）/血红素氧合酶1（HO-1）/核苷酸结合域样受体蛋白3（NLRP3）信号通路探讨益 气解毒生肌方治疗难治性糖尿病足湿热毒盛证的作用机制。【方法】 选取 2021年 2月至 2023年 2月海口市中医医院收治的难 治性糖尿病足湿热毒盛证患者80例，采用随机数字表法将患者随机分为对照组和观察组，每组各40例。对照组给予西医常 规治疗，观察组在对照组的基础上联合益气解毒生肌方治疗，疗程为4周并随访6个月。观察2组患者不同时间段的创面闭 合指数及治疗前后中医证候积分和血清白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、晚期糖基化终末产物（AGEs）、Nrf2、 HO-1、NLRP3水平的变化情况，并比较2组患者的临床疗效和复发率。【结果】（1）疗效方面，治疗4周后，观察组的总有效 率为 95.00%（38/40），对照组为 77.50%（31/40），组间比较（χ2检验），观察组的疗效明显优于对照组（P＜0.05）。（2）创面闭合 指数方面，2组组内不同时间段的创面闭合指数比较，均表现为治疗4周后>治疗3周后>治疗2周后>治疗1周后（P＜0.05）； 组间比较，观察组在治疗1～4周后的创面闭合指数均大于对照组（P＜0.05）。（3）中医证候积分方面，治疗后，2组患者的疮 面疼痛、疮面周围灼热、口渴、小便黄、大便干、溃疡等中医证候积分均较治疗前降低（P＜0.05），且观察组对各项中医证 候积分的降低幅度均明显优于对照组（P＜0.01）。（4）实验室指标方面，治疗后，2 组患者的血清 IL-6、TNF-α、AGEs、 NLRP3 水平均较治疗前降低（P＜0.05），血清 Nrf2、HO-1 水平均较治疗前升高（P＜0.05），且观察组对血清 IL-6、TNF-α、 AGEs、NLRP3水平的降低幅度及对血清Nrf2、HO-1水平的升高幅度均明显优于对照组（P＜0.05或P＜0.01）。（5）复发情况方 面，随访 6 个月，观察组的复发率为 6.45%（2/31），明显低于对照组的 29.63%（8/27），组间比较，差异有统计学意义（P＜ 0.05）。【结论】 在西医常规治疗基础上联合益气解毒生肌方治疗难治性糖尿病足湿热毒盛证患者疗效确切，可有效缓解临床 症状，加快创面闭合，降低复发率，其机制可能与下调 IL-6、TNF-α、AGEs、NLRP3水平，上调 Nrf2、HO-1水平，通过 Nrf2/HO-1/NLRP3信号通路减轻氧化应激和炎症反应有关。

Objective To investigate the mechanism of Yiqi Jiedu Shengji Formula in treating refractory diabetic foot with damp-heat toxin excess syndrome based on the nuclear factor E2-related factor 2（Nrf2）/heme oxygenase- 1（HO-1）/NOD-like receptor protein 3（NLRP3） signaling pathway. Methods Eighty patients with refractory diabetic foot of damp-heat toxin excess type admitted to Haikou Traditional Chinese Medicine Hospital between February 2021 and February 2023 were selected. They were randomly divided into a control group and an observation group using a random number table method，with 40 patients in each group. The control group received conventional western medical treatment， while the observation group received Yiqi Jiedu Shengji Formula in addition to the conventional treatment. The treatment course was 4 weeks，followed by a 6-month follow-up. The wound closure index at different time points，TCM syndrome scores，and serum levels of interleukin-6（IL-6）， tumor necrosis factor-alpha （TNF-α），advanced glycation end products （AGEs），Nrf2，HO-1，and NLRP3 were observed before and after treatment. Clinical efficacy and recurrence rates were compared between the two groups. Results （1） Regarding efficacy，after 4 weeks of treatment，the total effective rate was 95.00% （38/40） in the observation group and 77.50% （31/40） in the control group. Intergroup comparison （by chi-square test） showed that the efficacy in the observation group was significantly superior to that in the control group （P＜ 0.05）.（2）Regarding the wound closure index，intragroup comparisons at different time points in both groups showed that the index was increased with the treatment time：after 4 weeks of treatment > after 3 weeks > after 2 weeks > after 1 week （P＜0.05）. Intergroup comparisons revealed that the wound closure index in the observation group was greater than that in the control group at 1 to 4 weeks after treatment （P＜0.05）.（3） Regarding TCM syndrome scores，after treatment，scores for wound pain，peri-wound burning sensation，thirst，yellow urine， dry stool，and ulceration decreased compared to before treatment in both groups （P＜0.05）. The reduction in all TCM syndrome scores in the observation group was significantly greater than that in the control group （P＜0.01）. （4） Regarding laboratory indicators， after treatment， serum levels of IL-6， TNF- α， AGEs， and NLRP3 decreased compared to before treatment in both groups （P＜0.05）， while serum levels of Nrf2 and HO-1 increased （P＜0.05）. The reductions in serum IL-6，TNF-α，AGEs，and NLRP3 levels and the increases in serum Nrf2 and HO-1 levels in the observation group were significantly greater than those in the control group （P＜ 0.05 or P＜0.01）.（5） Regarding recurrence，during the 6-month follow-up，the recurrence rate was 6.45% （2/31） in the observation group， significantly lower than the 29.63% （8/27） in the control group， with a statistically significant difference between the groups （P＜0.05）. Conclusion The combination of Yiqi Jiedu Shengji Formula with conventional western medical treatment is effective for patients with refractory diabetic foot of damp-heat toxin excess type. It can effectively alleviate clinical symptoms，accelerate wound closure，and reduce the recurrence rate. Its mechanism may be related to downregulating IL-6，TNF-α，AGEs，and NLRP3 levels，upregulating Nrf2 and HO-1 levels， and thereby mitigating oxidative stress and inflammatory responses via the Nrf2/HO-1/NLRP3 signaling pathway.

R259.872

海南省卫生健康行业科研项目（编号：20A200076）