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目的：评估紫朱软膏对糖尿病足溃疡患者的临床疗效及其对患者创面中性粒细胞胞外陷阱（NETs）及炎症因子NOD样受体基因家族P3(NLRP3)、白细胞介素1(IL?1)表达的影响。方法：选取2024年1～6月在上海中医药大学附属曙光医院接受治疗的92例糖尿病足溃疡患者，在采取基础治疗后，随机分为试验组和对照组，每组46例，试验组采用紫朱软膏外敷，对照组采用外喷贝复济（bFGF）并用凡士林纱布外敷治疗。治疗8周后，比较两组的溃疡愈合率、溃疡面积和溃疡深度。采集两组患者治疗后第3天和第7天脱落的溃疡组织标本，采用苏木素?伊红（H&E）染色、免疫荧光染色和免疫组化观察创面炎性细胞数、NETs数、NLRP3和IL?1的表达。结果：与本组治疗前相比，两组患者的溃疡面积和溃疡深度均明显降低（P<0.01）。治疗后试验组的溃疡愈合率明显高于对照组（P<0.01），试验组的溃疡面积、溃疡深度明显低于对照组（P<0.01）。与正常皮肤组织相比，两组患者创面的炎性细胞数、NETs数及NLRP3、IL?1表达均明显升高（P<0.01）。与治疗前相比，治疗后两组患者的创面炎性细胞数、NETs数及NLRP3、IL?1表达均明显降低（P<0.01）。与对照组相比，试验组在治疗3 d和7 d后创面炎性细胞数、NETs数、NLRP3和IL?1表达明显降低（P<0.01）。结论：紫朱软膏外用具有明显的临床疗效，能够促进糖尿病足溃疡愈合。其机制可能涉及抑制NETs形成以及炎症因子NLRP3和IL?1的表达。
Abstract：Objective: To evaluate the clinical efficacy of Zizhu Ointment in the treatment of diabetic foot ulcer and its effects on neutrophil extracellular traps(NETs) and the expression of inflammatory factors NLRP3 and IL?1 in wound tissues. Methods: A total of 92 diabetic foot ulcer patients treated at Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine from January to June 2024 were randomly divided into an experimental group and a control group, each consisting of 46 cases, after receiving basic treatment. The experimental group applied Zizhu Ointment topically, while the control group applied basic fibroblast growth factor(bFGF) spray and covered with Vaseline gauze for treatment. After 8 weeks of treatment, the ulcer healing rate, ulcer area and ulcer depth of both groups were compared. Specimens of ulcer tissue shed on the 3 rd and 7 th day after treatment from both groups were collected and observed for the number of inflammatory cells, NETs, and the expression of NL?RP3 and IL?1 in the wound using Hematoxylin?Eosin(H&E) staining, immunofluorescence staining, and immunohistochemistry. Results: Compared to before treatment in the same group, the ulcer area and ulcer depth in both groups were significantly reduced(P<0.01). After treatment, the ulcer healing rate in the experimental group was significantly higher than that in the control group(P<0.01), and the ulcer area, ulcer depth in the experimental group were significantly lower than those in the control group(P<0.01). Compared to normal skin tissue, the number of inflammatory cells, NETs, and the expression of NLRP3 and IL?1 in the wound tissues of both groups were significantly increased(P<0.01). Compared to before treatment, the number of inflammatory cells, NETs, NLRP3 and IL?1 expression in the wound of the two groups were significantly decreased after treatment(P<0.01). Compared to the control group, the number of inflammatory cells, NETs, and the expression of NLRP3 and IL?1 in the wound tissues of the experimental group were significantly reduced after 3 and 7 days of treatment(P<0.01). Conclusion: The external use of Zizhu Ointment in the treatment of diabetic foot ulcer has significant clinical efficacy and can promote the healing of diabetic foot ulcers. Its mechanism may involve the inhibition of NETs formation and the expression of inflammatory factors NLRP3 and IL?1.
1 Tang WH, Zhao YN, Cheng ZX, et al. Risk factors fordiabetic foot ulcers:A systematic review and meta?analy?sis[J].Vascular,2024, 32(3):661?669.
2 Kaka AS, Landsteiner A, Ensrud KE, et al. Risk pre?diction models for diabetic foot ulcer development or am?putation:A review of reviews[J]. J Foot Ankle Res,2023, 16(1):13.
3 Mcdermott K, Fang M, Boulton AJ, et al. Etiology, ep?idemiology, and disparities in the burden of diabetic footulcers[J]. Diabetes Care, 2023, 46(1):209?221.
4 Rastogi A, Goyal G, Kesavan R, et al. Long term out?comes after incident diabetic foot ulcer:Multicenterlarge cohort prospective study(EDI?FOCUS investiga?tors) epidemiology of diabetic foot complications study:Epidemiology of diabetic foot complications study[J]. Di?abetes Res Clin Pract, 2020, 162:108113.
5杨硕菲，陈亮，王浙宇，等.中性粒细胞陷阱网对糖尿病足临床愈合结局的预测价值[J].中国临床医学，2023, 30(1):24?30.Yang SF, Chen L, Wang ZY, et al. Predictive value ofneutrophil extracellular traps for clinical healing outcomeof diabetic foot ulcer[J]. Chin J Clin Med, 2023,30(1):24?30.
6 Zhu ZY, Zhou SZ, Li SC, et al. Neutrophil extracellu?lar traps in wound healing[J]. Trends Pharmacol Sci,2024, 45(31):1033?1045.
7 Yang SF, Gu ZC, Lu C, et al. Neutrophil extracellulartraps are markers of wound healing impairment in pa?tients with diabetic foot ulcers treated in a multidisci?plinary setting[J]. Adv Wound Care, 2020, 9(1):16?27.
8 Hidalgo A, Libby P, Soehnlein O, et al. Neutrophil ex?tracellular traps:From physiology to pathology[J]. Car?diovasc Res, 2022, 118(13):2737?2753.
9 Zhu SN, Yu Y, Ren Y, et al. The emerging roles ofneutrophil extracellular traps in wound healing[J]. CellDeath Dis, 2021, 12(11):984.
10 Heuer A, Stiel C, Elrod J, et al. Therapeutic targetingof neutrophil extracellular traps improves primary andsecondary intention wound healing in mice[J]. Front Im?munol, 2021, 12:614347.
11 Fu JN, Wu H. Structural mechanisms of NLRP3 inflam?masome assembly and activation[J]. Annu Rev Immu?nol, 2023, 41(1):301?316.
12 Heger LA, Schommer N, Van Bruggen S, et al. Neu?trophil NLRP3 promotes cardiac injury following acutemyocardial infarction through IL?1β production, VWFrelease and NET deposition in the myocardium[J]. SciRep, 2024, 14(1):14524.
13 Lee MK, Sreejit G, Nagareddy PR, et al. Attack of theNETs! NETosis primes IL?1β?mediated inflammationin diabetic foot ulcers[J]. Clin Sci, 2020, 134(12):1399?1401.
14 Yang SF, Feng Y, Chen L, et al. Disulfiram acceleratesdiabetic foot ulcer healing by blocking NET formationvia suppressing the NLRP3/Caspase?1/GSDMD path?way[J]. Translat Res, 2023, 254:115?127.
15樊炜静，王宏飞，杨宝钟，等.论煨脓长肉理论在慢性难愈性溃疡治疗中的应用[J].中国中医药信息杂志，2022, 29(11):138?140.Fan WJ, Wang HF, Yang BZ, et al. Application of thetheory of simmering pus and growing flesh in thetreatment of chronic refractory ulcer[J]. Chin J InfTradit Chin Med, 2022, 29(11):138?140.
16李文惠，杨晓，闫少庆，等.紫朱软膏干预糖尿病足愈合过程中细胞因子表达[J].中国老年学杂志，2020, 40(6):1159?1161.Li WH, Yang X, Yan SQ, et al. Changes of cytokinesin the healing process of diabetic foot and the effect ofZizhu ointment[J]. Chin J Gerontol, 2020, 40(6):1159?1161.
17樊炜静，王宏飞，杨宝钟，等.煨脓长肉中医外治方案治疗Wagner 2?3级糖尿病足溃疡的临床疗效[J].中国实验方剂学杂志，2022, 28(14):107?114.Fan WJ, Wang HF, Yang BZ, et al. Clinicalobservation on Wagner 2~3 diabetic foot ulcer treated byTCM external treatment scheme for Euriching pus fortissue growth[J]. Chin J Exp Tradit Med Formulae,2022, 28(14):107?114.
18韩强，柳国斌，严仕梦，等.紫朱软膏通过抑制炎症反应促进糖尿病足溃疡愈合的研究[J].海南医学院学报，2020, 26(21):1617?1624,1629.Han Q, Liu GB, Yan SM, et al. Zizhu ointmentpromote shealing of diabetic foot ulcers by inhibitinginflammatory reaction[J]. J Hainan Med Univ, 2020, 26(21):1617?1624,1629.
19黄仁燕，柳国斌.中医特色外治方案治疗Wagner2~4级糖尿病足溃疡临床观察[J].中华中医药杂志，2019,34(5):2117?2120.Huang RY, Liu GB. Clinical observation on thetreatment of Wagner Class 2?4 diabetic foot ulcer withcharacteristic external therapy scheme of traditionalChinese medicine[J]. China J Trad Chin Med Pharm,2019, 34(5):2117?2120.
20杨婷，邱祥，柳国斌.奚氏中医外科技术治疗糖尿病足溃疡180例临床疗效观察[J].天津中医药大学学报，2016,33(35):298?301.Yang T, Qiu X, Liu GB. The observation of the clinicaleffect of Xishi external treatment of traditional Chinesemedicine on diabetic foot ulcer[J]. J Tianjin Univ TraditChin Med, 2016,33(35):298?301.
21武宁.内科综合药物治疗糖尿病足效果观察[J].临床合理用药杂志，2020, 13(3B):135?136.Wu N. Observation on the effect of medicalcomprehensive medicine on diabetes foot[J]. Chin J ClinRational Drug Use, 2020, 13(3B):135?136.
22梅喜庆，杨萍萍，黎英豪.双黄液辅助治疗促进糖尿病足溃疡愈合的临床疗效观察[J].中华中医药杂志，2014, 29(9):3028?3030.Mei XQ, Yang PP, Li YH. Clinical observation ofShuanghuang Decoction′s adjuvant therapy on promotingthe healing of diabetic foot ulcer[J]. China J Tradit ChinMed Pharm, 2014, 29(9):3028?3030.
23中华医学会糖尿病学分会.中国2型糖尿病防治指南（2020年版）[J].中国实用内科杂志，2021, 41(8):668?695, 41(9):757?784.Chinese Diabetes Society. 2020 Chinese type 2 diabetesprevention and treatment comprehensive guide[J]. ChinJ Pract Intern Med, 2021, 41(8):668?695, 41(9):757?784.
24中国中西医结合学会周围血管病专业委员会.中西医结合防治糖尿病足中国专家共识（第1版）[J].血管与腔内血管外科杂志，2019, 5(5):379?402.Peripheral Vascular Disease Professional Committee ofChinese Association of Integrative Medicine. Chineseexpert consensus on the prevention and management ofdiabetic foot with integrative medicine(1st edition)[J]. JVasc Endovasc Surg, 2019, 5(5):379?402.
25 Huang W, Jiao J, Liu J, et al. MFG?E8 accelerateswound healing in diabetes by regulating"NLRP3inflammasome?neutrophil extracellular traps"axis[J].Cell Death Discov, 2020, 6(1):84.
26樊炜静，李文惠，卢慧敏，等.基于煨脓长肉理论探讨紫朱软膏通过NLRP3逆转糖尿病难愈性创面巨噬细胞胞葬逃逸的机制研究[J].中医药学报，2023, 51(11):29?35.Fan WJ, Li WH, Lu HM, et al. Exploring themechanism of hematite ointment to reverse themacrophage efferocytosis escape of diabetic refractorywound through NLRP3 based on the theory of weinongzhangrou[J]. Acta Chin Med Pharmacol, 2023, 51(11):29?35.
27黄仁燕，闫少庆，杨晓，等.紫朱软膏治疗非缺血型糖尿病足溃疡临床疗效及其对细胞免疫水平的影响[J].山东中医杂志，2022, 41(10):1096?1101.Huang RY, Yan SQ, Yang X, et al. Effect of ZizhuOintment on non?ischemic diabetic foot ulcer and cellularimmunity level[J]. Shandong J Tradit Chin Med, 2022,41(10):1096?1101.
28 Chen WW, Chen K, Xu ZX, et al. Neutrophil?to?lym?phocyte ratio and platelet?to?lymphocyte ratio predictmortality in patients with diabetic foot ulcers undergoingamputations[J]. Diabetes Metab Syndr Obes, 2021:821?829.
29 Altay FA, Kuzi S, Altay M, et al. Predicting diabeticfoot ulcer infection using the neutrophil?to?lymphocyte ra?tio:A prospective study[J]. J Wound Care, 2019, 28(9):601?607.
30 Liu D, Yang PL, Gao M, et al. NLRP3 activation in?duced by neutrophil extracellular traps sustains inflamma?tory response in the diabetic wound[J]. Clin Sci, 2019,133(4):565?582.
31 Ma XX, Liu QK, Kuai L, et al. The role of neutrophilsin diabetic ulcers and targeting therapeutic strategies[J].Int Immunopharmacol, 2023, 124:110861.
32 Ma HK, Yao WT, Peng B, et al. Mercury?containingpreparations attenuate neutrophil extracellular trap forma?tion in mice and humans through inhibiting the ERK1/2pathway[J]. J Ethnopharmacol, 2023:117421.
33马慧可，姚文涛，刘欣，等.紫草素对糖尿病小鼠中性粒细胞胞外诱捕网表达的影响[J].中国中西医结合外科杂志，2023, 29(3):377?382.Ma HK, Yao WT, Liu X, et al. Effects of Shikoninonthe expressionof neutrophils extracellular traps induced indiabetic mice[J]. Chin J Surg Integr Tradit WesternMed, 2023, 29(3):377?382.
34胡啸明，黄仁燕，韩强，等.紫朱软膏对急性创面愈合过程中IL?1β、MMP?9和TGF?β的作用及自噬相关性研究[J].中医药学报，2020, 48(11):1?9.Hu XM, Huang RY, Han Q, et al. Effect of ZizhuOintment on IL?1β, MMP?9 and TGF?β during acutewound healing and correlation of autophagy and wouldhealing[J]. Acta Chin Med Pharmacol, 2020, 48(11):1?9.
基本信息:
DOI：10.13210/j.cnki.jhmu.20250108.002
中图分类号:R259
引用信息:
[1]孙健,樊炜静,袁美杰,等.紫朱软膏治疗糖尿病足溃疡的临床疗效及对创面中性粒细胞胞外陷阱和NLRP3、IL-1表达的影响[J].海南医科大学学报,2026,32(01):1-9.DOI:10.13210/j.cnki.jhmu.20250108.002.
基金信息:
国家自然科学基金项目（82274528）; 浦东新区卫生健康委员会科研项目（PW2020E?4）~~
2025-01-09
2025-01-09
2025-01-09