-
摘要: 糖尿病足溃疡患病人数逐年递增,糖尿病足溃疡难愈合,给国家及个人带来巨大负担。如何加速糖尿病足溃疡愈合成为研究的重点,但目前其难愈合机制尚未被完全阐明,各机制之间关联性不高,因此其临床标准化和精准化诊疗仍面临若干挑战。该文结合国内外临床研究与基础研究进展,围绕慢性炎症、细菌生物膜形成、高氧化应激、生长因子抑制、微循环障碍、晚期糖基化终末产物积累等导致糖尿病足溃疡难愈合的具体机制进行综述。Abstract: The number of patients with diabetic foot ulcer (DFU) has increased progressively year by year. Refractory DFU has brought great burden to the country and individuals. How to accelerate the healing of DFU has become the main emphasis of research. However currently, the mechanism of its refractory healing is not fully elucidated, and the correlation between the various mechanisms are not high. Therefore, its clinical standardization, and precise clinical diagnosis and treatment still face several challenges. Based on the progress of clinical research and basic research at home and abroad, this paper reviewed the specific mechanisms that lead to refractory DFU, with the focus on chronic inflammation, bacteria biofilm formation, high oxidative stress, growth factor inhibition, impaired microcirculation, and accumulation of advanced glycation end products.
-
Key words:
- Diabetic foot /
- Biofilms /
- Microcirculation /
- Wound repair /
- Chronic inflammation /
- Impaired healing /
- Mechanism
-
[1] JiangYF, WangXM, XiaL, et al. A cohort study of diabetic patients and diabetic foot ulceration patients in China[J]. Wound Repair Regen,2015,23(2):222-230. DOI: 10.1111/wrr.12263. [2] ArmstrongDG, WrobelJ, RobbinsJM. Guest Editorial: are diabetes-related wounds and amputations worse than cancer?[J]. Int Wound J,2007,4(4):286-287. DOI: 10.1111/j.1742-481X.2007.00392.x. [3] ArmstrongDG, LaveryLA, WrobelJS, et al. Quality of life in healing diabetic wounds: does the end justify the means?[J]. J Foot Ankle Surg,2008,47(4):278-282. DOI: 10.1053/j.jfas.2008.02.015. [4] LiuD, YangPL, GaoM, et al. NLRP3 activation induced by neutrophil extracellular traps sustains inflammatory response in the diabetic wound[J]. Clin Sci (Lond),2019,133(4):565-582. DOI: 10.1042/CS20180600. [5] LouiselleAE, NiemiecSM, ZgheibC, et al. Macrophage polarization and diabetic wound healing[J]. Transl Res,2021,236:109-116. DOI: 10.1016/j.trsl.2021.05.006. [6] JulierZ, ParkAJ, BriquezPS, et al. Promoting tissue regeneration by modulating the immune system[J]. Acta Biomater,2017,53:13-28. DOI: 10.1016/j.actbio.2017.01.056. [7] KalekarLA, RosenblumMD. Regulatory T cells in inflammatory skin disease: from mice to humans[J]. Int Immunol,2019,31(7):457-463. DOI: 10.1093/intimm/dxz020. [8] BusSA, LaveryLA, Monteiro-SoaresM, et al. Guidelines on the prevention of foot ulcers in persons with diabetes (IWGDF 2019 update)[J]. Diabetes Metab Res Rev,2020,36(Suppl 1):Se3269. DOI: 10.1002/dmrr.3269. [9] FalangaV. Wound healing and its impairment in the diabetic foot[J]. Lancet,2005,366(9498):1736-1743. DOI: 10.1016/S0140-6736(05)67700-8. [10] MaYG. Role of neutrophils in cardiac injury and repair following myocardial infarction[J]. Cells,2021,10(7):1676. DOI: 10.3390/cells10071676. [11] ThiamHR, WongSL, WagnerDD, et al. Cellular mechanisms of NETosis[J]. Annu Rev Cell Dev Biol,2020,36:191-218. DOI: 10.1146/annurev-cellbio-020520-111016. [12] 崔胜勇,刘琰,章雄. 巨噬细胞功能障碍与糖尿病慢性难愈创面的关系[J]. 中华烧伤杂志,2014,30(3):264-269. DOI: 10.3760/cma.j.issn.1009-2587.2014.03.019. [13] LucasT, WaismanA, RanjanR, et al. Differential roles of macrophages in diverse phases of skin repair[J]. J Immunol,2010,184(7):3964-3977. DOI: 10.4049/jimmunol.0903356. [14] AitchesonSM, FrentiuFD, HurnSE, et al. Skin wound healing: normal macrophage function and macrophage dysfunction in diabetic wounds[J]. Molecules,2021,26(16):4917. DOI: 10.3390/molecules26164917. [15] JettenN, VerbruggenS, GijbelsMJ, et al. Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo[J]. Angiogenesis,2014,17(1):109-118. DOI: 10.1007/s10456-013-9381-6. [16] RaiV, MoellmerR, AgrawalDK. The role of CXCL8 in chronic nonhealing diabetic foot ulcers and phenotypic changes in fibroblasts: a molecular perspective[J]. Mol Biol Rep,2022,49(2):1565-1572. DOI: 10.1007/s11033-022-07144-3. [17] LaroucheJ, SheoranS, MaruyamaK, et al. Immune regulation of skin wound healing: mechanisms and novel therapeutic targets[J]. Adv Wound Care (New Rochelle),2018,7(7):209-231. DOI: 10.1089/wound.2017.0761. [18] SmigielKS, ParksWC. Macrophages, wound healing, and fibrosis: recent insights[J]. Curr Rheumatol Rep,2018,20(4):17. DOI: 10.1007/s11926-018-0725-5. [19] RehakL, GiuratoL, MeloniM, et al. The immune-centric revolution in the diabetic foot: monocytes and lymphocytes role in wound healing and tissue regeneration-a narrative review[J]. J Clin Med,2022,11(3):889. DOI: 10.3390/jcm11030889. [20] LeeMKS, SreejitG, NagareddyPR, et al. Attack of the NETs! NETosis primes IL-1β-mediated inflammation in diabetic foot ulcers[J]. Clin Sci (Lond),2020,134(12):1399-1401. DOI: 10.1042/CS20200240. [21] ShoflerD, RaiV, MansagerS, et al. Impact of resolvin mediators in the immunopathology of diabetes and wound healing[J]. Expert Rev Clin Immunol,2021,17(6):681-690. DOI: 10.1080/1744666X.2021.1912598. [22] HallCW, MahTF. Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria[J]. FEMS Microbiol Rev,2017,41(3):276-301. DOI: 10.1093/femsre/fux010. [23] SunHM, PulakatL, AndersonDW. Challenges and new therapeutic approaches in the management of chronic wounds[J]. Curr Drug Targets,2020,21(12):1264-1275. DOI: 10.2174/1389450121666200623131200. [24] AfonsoAC, OliveiraD, SaavedraMJ, et al. Biofilms in diabetic foot ulcers: impact, risk factors and control strategies[J]. Int J Mol Sci,2021,22(15):8278. DOI: 10.3390/ijms22158278. [25] PasupuletiVR, ArigelaCS, GanSH, et al. A review on oxidative stress, diabetic complications, and the roles of honey polyphenols[J]. Oxid Med Cell Longev,2020,2020:8878172. DOI: 10.1155/2020/8878172. [26] DengLL, DuCZ, SongPY, et al. The role of oxidative stress and antioxidants in diabetic wound healing[J]. Oxid Med Cell Longev,2021,2021:8852759. DOI: 10.1155/2021/8852759. [27] PatelS, SrivastavaS, SinghMR, et al. Mechanistic insight into diabetic wounds: pathogenesis, molecular targets and treatment strategies to pace wound healing[J]. Biomed Pharmacother,2019,112:108615. DOI: 10.1016/j.biopha.2019.108615. [28] HinchliffeRJ, ForsytheRO, ApelqvistJ, et al. Guidelines on diagnosis, prognosis, and management of peripheral artery disease in patients with foot ulcers and diabetes (IWGDF 2019 update) [J]. Diabetes Metab Res Rev,2020,36(Suppl 1):Se3276. DOI: 10.1002/dmrr.3276. [29] GrennanD. Diabetic foot ulcers[J]. JAMA, 2019,321(1):114. DOI: 10.1001/jama.2018.18323. [30] 陆树良,谢挺,牛轶雯. 创面难愈机制研究——糖尿病皮肤的“微环境污染”[J]. 中华烧伤杂志,2008,24(1):3-5. DOI: 10.3760/cma.j.issn.1009-2587.2008.01.002. [31] GuoYY, LinC, XuP, et al. AGEs induced autophagy impairs cutaneous wound healing via stimulating macrophage polarization to M1 in diabetes[J]. Sci Rep, 2016,6:36416. DOI: 10.1038/srep36416. [32] KangYT, ZhengCL, YeJN, et al. Effects of advanced glycation end products on neutrophil migration and aggregation in diabetic wounds[J]. Aging (Albany NY),2021,13(8):12143-12159. DOI: 10.18632/aging.202924. [33] ChoH, BlatchleyMR, DuhEJ, et al. Acellular and cellular approaches to improve diabetic wound healing[J]. Adv Drug Deliv Rev,2019,146:267-288. DOI: 10.1016/j.addr.2018.07.019. [34] 付小兵. 不忘初心 牢记使命 努力把中国创面修复科建设好发展好[J]. 中华烧伤杂志,2020,36(1):1-4. DOI: 10.3760/cma.j.issn.1009-2587.2020.01.001. [35] 付小兵. 战时治烧伤,平时治创面:有关烧伤学科发展的一点思考[J]. 中华烧伤杂志,2018,34(7):434-436. DOI: 10.3760/cma.j.issn.1009-2587.2018.07.002. [36] LandénNX, LiDQ, StåhleM. Transition from inflammation to proliferation: a critical step during wound healing[J]. Cell Mol Life Sci,2016,73(20):3861-3885. DOI: 10.1007/s00018-016-2268-0. [37] SharifiS, HajipourMJ, GouldL, et al. Nanomedicine in healing chronic wounds: opportunities and challenges[J]. Mol Pharm,2021,18(2):550-575. DOI: 10.1021/acs.molpharmaceut.0c00346. [38] PougetC, Dunyach-RemyC, PantelA, et al. Biofilms in diabetic foot ulcers: significance and clinical relevance[J]. Microorganisms,2020,8(10):1580. DOI: 10.3390/microorganisms8101580. [39] EmingSA, WynnTA, MartinP. Inflammation and metabolism in tissue repair and regeneration[J]. Science,2017,356(6342):1026-1030. DOI: 10.1126/science.aam7928. [40] ZhangJJ, ZhouR, XiangCP, et al. Huangbai liniment accelerated wound healing by activating Nrf2 signaling in diabetes[J]. Oxid Med Cell Longev,2020,2020:4951820. DOI: 10.1155/2020/4951820. [41] YangWF, WeiQ, TongQ, et al. Traditional chinese medicine Tanreqing inhibits quorum sensing systems in pseudomonas aeruginosa[J]. Front Microbiol,2020,11:517462. [42] 王宁,鞠上. 缺血性糖尿病足创面的处理原则与方法[J]. 中国临床医生杂志,2021,49(12):1393-1396. DOI: 10.3969/j.issn.2095-8552.2021.12.003. [43] WangAP, LvGZ, ChengXB, et al. Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition)[J/OL]. Burns Trauma,2020,8:tkaa017[2022-02-27]. https://pubmed.ncbi.nlm.nih.gov/32685563/.DOI: 10.1093/burnst/tkaa017. [44] ForsytheRO, BrownriggJ, HinchliffeRJ. Peripheral arterial disease and revascularization of the diabetic foot[J]. Diabetes Obes Metab,2015,17(5):435-444. DOI: 10.1111/dom.12422.
点击查看大图
计量
- 文章访问数: 462
- HTML全文浏览量: 58
- PDF下载量: 103
- 被引次数: 0