五虫通络丸治疗痰瘀阻络型糖尿病下肢血管病变的前瞻性随机安慰剂对照临床研究

A Prospective, Randomized, Placebo-Controlled Clinical Study of Wuchong Tongluo Pill in the Treatment of Diabetic Lower Extremity Vascular Disease with Phlegm-Blood Stasis Obstructing Collaterals Pattern

摘要: 目的：糖尿病下肢血管病变(LEAD)是2型糖尿病常见慢性并发症，也是导致糖尿病患者截肢的重要原因；痰瘀阻络型为其临床常见证型，但目前尚缺乏高质量中医药随机对照研究证据。本研究旨在评价五虫通络丸联合基础治疗对痰瘀阻络型LEAD患者的临床疗效。方法：采用前瞻性、单中心、随机、安慰剂对照设计，纳入2023年9月至2024年12月就诊的痰瘀阻络型LEAD患者82例，随机分为实验组与对照组，各41例。实验组给予基础治疗联合五虫通络丸，对照组给予基础治疗联合中药安慰剂。比较两组治疗前后足背经皮氧分压(TcPO2)、踝肱指数(ABI)、糖代谢指标(FBG、2 hPG、HbA1c)、血液流变学指标及中医证候总积分变化，并采用Pearson相关性热力图分析各指标间关联。结果：实验组TcPO2改善幅度显著优于对照组(16.5→37.8 mmHg vs 15.5→32.7 mmHg, p < 0.001)；ABI组间差异具有统计学意义(1.011 vs 0.957, p = 0.0066)；2 hPG变化量组间差异极显著(p < 0.001)，FBG和HbA1c差异无统计学意义；全血中切粘度、全血低切粘度及红细胞聚集指数三项指标实验组改善均显著优于对照组(均p < 0.001)；中医证候总积分实验组中位变化量约−12分，显著优于对照组的约−4分(p < 0.001)；相关性分析提示血糖控制、血液流变学与微循环灌注指标间存在多维度协同变化。结论：五虫通络丸可显著改善痰瘀阻络型LEAD患者的下肢微循环灌注、血管功能、血液流变学状态及中医证候，且安全性良好。未来需开展多中心、大样本、长疗程研究，并结合湿实验深入探讨其作用机制。

Abstract: Objective: Diabetic lower extremity vascular disease (LEAD) is a common chronic complication of type 2 diabetes mellitus and a major cause of amputation in patients with diabetes. The phlegm-blood stasis obstructing collaterals pattern is a common clinical pattern; however, high-quality evidence from randomized controlled trials of traditional Chinese medicine interventions is still lacking. This study aimed to evaluate the clinical efficacy of Wuchong Tongluo Pill combined with basic therapy in patients with LEAD of the phlegm-blood stasis obstructing collaterals pattern. Methods: A prospective, single-center, randomized, placebo-controlled design was adopted. Eighty-two patients with LEAD of the phlegm-blood stasis obstructing collaterals pattern who visited the hospital between September 2023 and December 2024 were enrolled and randomly divided into an experimental group and a control group, with 41 cases in each group. The experimental group received basic therapy combined with Wuchong Tongluo Pill, while the control group received basic therapy combined with a Chinese herbal placebo. Changes in transcutaneous oxygen pressure of the dorsum of the foot (TcPO2), ankle-brachial index (ABI), glucose metabolic indices (FBG, 2 hPG, and HbA1c), hemorheological indices, and total TCM syndrome score were compared between the two groups before and after treatment. Pearson correlation heatmaps were used to analyze the associations among the indices. Results: The improvement in TcPO2 in the experimental group was significantly greater than that in the control group (16.5→37.8 mmHg vs 15.5→32.7 mmHg, p < 0.001). The between-group difference in ABI was statistically significant (1.011 vs 0.957, p = 0.0066). The between-group difference in the change in 2 hPG was highly significant (p < 0.001), while no statistically significant differences were observed in FBG or HbA1c. The improvements in whole blood viscosity at middle shear rate, whole blood viscosity at low shear rate, and erythrocyte aggregation index in the experimental group were all significantly greater than those in the control group (all p < 0.001). The median change in the total TCM syndrome score in the experimental group was approximately −12 points, which was significantly better than approximately −4 points in the control group (p < 0.001). Correlation analysis suggested multidimensional coordinated changes among glycemic control, hemorheological indices, and microcirculatory perfusion indices. Conclusion: Wuchong Tongluo Pill can significantly improve lower-limb microcirculatory perfusion, vascular function, hemorheological status, and TCM syndrome in patients with LEAD of the phlegm-blood stasis obstructing collaterals pattern, with a good safety profile. Future multicenter, large-sample, long-course studies combined with wet experiments are needed to further explore its mechanism of action.