-
摘要: 糖尿病创面是糖尿病并发症,其难以愈合,易转为慢性创面。与普通创面愈合相比,糖尿病创面停留在炎症期,无法进入增殖期,原因为促炎性细胞因子比例增加造成炎症细胞比例失调,大量炎症因子堆积。炎症因子的产生、释放与细胞焦亡密切相关。细胞焦亡是一种炎症细胞程序性死亡方式。在炎症小体介导下,细胞焦亡通过典型与非典型炎症小体信号通路转导,造成细胞膜上形成孔隙,诱发细胞死亡,并在此过程中释放大量促炎性细胞因子,维持创面的炎症环境,阻碍糖尿病创面向增殖期、重塑期发展,从而抑制糖尿病创面愈合。该文就细胞焦亡机制及细胞焦亡对糖尿病创面的影响、抑制细胞焦亡在糖尿病创面治疗中的潜在意义以及存在的相关问题进行综述。Abstract: Diabetic wound is a complication of diabetes, which is difficult to heal and easy to turn into chronic wound. Compared with ordinary wound healing, diabetic wounds stay in the inflammatory stage and can not enter the proliferative stage. This is because the proportion of pro-inflammatory cytokines increases, leading to the imbalance of inflammatory cells and the accumulation of a large number of inflammatory factors. The production and release of inflammatory factors is closely related to pyroptosis. Pyroptosis is a kind of programmed death mode of inflammatory cells. Mediated by inflammasome, pyroptosis is transduced through typical and atypical inflammasome signaling pathways, resulting in the formation of pores on the cell membrane and inducing cell death. In this process, a large number of pro-inflammatory cytokines are released to maintain the inflammatory environment of wounds, hindering the development of diabetic wounds to the proliferative stage and remodeling stage, thus inhibiting the healing of diabetic wounds. This article reviews the mechanism of pyroptosis and its effect on diabetic wounds, the potential significance of inhibiting pyroptosis in the treatment of diabetic wounds, and the existing problems.
-
Key words:
- Pyroptosis /
- Inflammation /
- Cytokines /
- Diabetes complications /
- Wound healing /
- Inflammasome
-
参考文献
(37) [1] ChenL, GaoY, LiY, et al. Severe intermittent hypoxia modulates the macrophage phenotype and impairs wound healing through downregulation of HIF-2α[J]. Nat Sci Sleep, 2022,14:1511-1520. DOI: 10.2147/NSS.S382275. [2] WeiX, XieF, ZhouX, et al. Role of pyroptosis in inflammation and cancer[J]. Cell Mol Immunol, 2022,19(9):971-992. DOI: 10.1038/s41423-022-00905-x. [3] MandalR, BarrónJC, KostovaI, et al. Caspase-8: the double-edged sword[J]. Biochim Biophys Acta Rev Cancer, 2020,1873(2):188357. DOI: 10.1016/j.bbcan.2020.188357. [4] 金煦,万佳,段淑芳,等. 布鲁顿酪氨酸激酶在内毒素/脂多糖诱导烫伤小鼠肠道细胞焦亡中的作用[J]. 中华烧伤杂志,2021,37(6):546-554.DOI: 10.3760/cma.j.cn501120-20210119-00027. [5] WeiSQ, FengM, ZhangSD. Molecular characteristics of cell pyroptosis and its inhibitors: a review of activation, regulation, and inhibitors[J]. Int J Mol Sci, 2022,23(24):16115. DOI: 10.3390/ijms232416115. [6] ShiJJ, GaoW, ShaoF. Pyroptosis: gasdermin-mediated programmed necrotic cell death[J]. Trends Biochem Sci, 2017,42(4):245-254. DOI: 10.1016/j.tibs.2016.10.004. [7] ShiJ, ZhaoY, WangK, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death[J]. Nature, 2015,526(7575):660-665. DOI: 10.1038/nature15514. [8] DingY, DingX, ZhangH, et al. Relevance of NLRP3 inflammasome-related pathways in the pathology of diabetic wound healing and possible therapeutic targets[J]. Oxid Med Cell Longev, 2022,2022:9687925. DOI: 10.1155/2022/9687925. [9] SeokJK, KangHC, ChoYY, et al. Regulation of the NLRP3 inflammasome by post-translational modifications and small molecules[J]. Front Immunol, 2021,11:618231. DOI: 10.3389/fimmu.2020.618231. [10] ZuoY, ChenL, GuH, et al. GSDMD-mediated pyroptosis: a critical mechanism of diabetic nephropathy[J]. Expert Rev Mol Med, 2021,23:e23. DOI: 10.1017/erm.2021.27. [11] WuC, LuW, ZhangY, et al. Inflammasome activation triggers blood clotting and host death through pyroptosis[J]. Immunity, 2019,50(6):1401-1411.e4. DOI: 10.1016/j.immuni.2019.04.003. [12] HuangC, OgawaR. Role of inflammasomes in keloids and hypertrophic scars-lessons learned from chronic diabetic wounds and skin fibrosis[J]. Int J Mol Sci, 2022,23(12):6820. DOI: 10.3390/ijms23126820. [13] BrazilJC, QuirosM, NusratA, et al. Innate immune cell-epithelial crosstalk during wound repair[J]. J Clin Invest, 2019,129(8):2983-2993. DOI: 10.1172/JCI124618. [14] LiuD, YangP, 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. [15] DominicA, LeNT, TakahashiM. Loop between NLRP3 inflammasome and reactive oxygen species[J]. Antioxid Redox Signal, 2022,36(10/11/12):784-796. DOI: 10.1089/ars.2020.8257. [16] ZhouR, YazdiAS, MenuP, et al. A role for mitochondria in NLRP3 inflammasome activation[J]. Nature, 2011,469(7329):221-225. DOI: 10.1038/nature09663. [17] DongXH, HeY, YeF, et al. Vitamin D3 ameliorates nitrogen mustard-induced cutaneous inflammation by inactivating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway[J]. Clin Transl Med, 2021,11(2):e312. DOI: 10.1002/ctm2.312. [18] GustinA, KirchmeyerM, KoncinaE, et al. NLRP3 inflammasome is expressed and functional in mouse brain microglia but not in astrocytes[J]. PLoS One, 2015,10(6):e0130624. DOI: 10.1371/journal.pone.0130624. [19] OrlowskiGM, ColbertJD, SharmaS, et al. Multiple cathepsins promote pro-IL-1β synthesis and NLRP3-mediated IL-1β activation[J]. J Immunol, 2015,195(4):1685-1697. DOI: 10.4049/jimmunol.1500509. [20] SharmaBR, KannegantiTD. NLRP3 inflammasome in cancer and metabolic diseases[J]. Nat Immunol, 2021,22(5):550-559. DOI: 10.1038/s41590-021-00886-5. [21] PukstadBS, RyanL, FloTH, et al. Non-healing is associated with persistent stimulation of the innate immune response in chronic venous leg ulcers[J]. J Dermatol Sci, 2010,59(2):115-122. DOI: 10.1016/j.jdermsci.2010.05.003. [22] WangL, SongD, WeiC, et al. Telocytes inhibited inflammatory factor expression and enhanced cell migration in LPS-induced skin wound healing models in vitro and in vivo[J]. J Transl Med, 2020,18(1):60. DOI: 10.1186/s12967-020-02217-y. [23] MuX, WuX, HeW, et al. Pyroptosis and inflammasomes in diabetic wound healing[J]. Front Endocrinol (Lausanne), 2022,13:950798. DOI: 10.3389/fendo.2022.950798. [24] QingL, FuJ, WuP, et al. Metformin induces the M2 macrophage polarization to accelerate the wound healing via regulating AMPK/mTOR/NLRP3 inflammasome singling pathway[J]. Am J Transl Res, 2019,11(2):655-668. [25] ZhaoY, WangQ, YanS, et al. Bletilla striata polysaccharide promotes diabetic wound healing through inhibition of the NLRP3 inflammasome[J]. Front Pharmacol, 2021,12:659215. DOI: 10.3389/fphar.2021.659215. [26] SunX, WangX, ZhaoZ, et al. Paeoniflorin inhibited nod-like receptor protein-3 inflammasome and NF-κB-mediated inflammatory reactions in diabetic foot ulcer by inhibiting the chemokine receptor CXCR2[J]. Drug Dev Res, 2021,82(3):404-411. DOI: 10.1002/ddr.21763. [27] HuJJ, LiuX, XiaSY, et al. FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation[J]. Nat Immunol, 2020,21(7):736-745. DOI: 10.1038/s41590-020-0669-6. [28] HumphriesF, Shmuel-GaliaL, Ketelut-CarneiroN, et al. Succination inactivates gasdermin D and blocks pyroptosis[J]. Science, 2020,369(6511):1633-1637. DOI: 10.1126/science.abb9818. [29] LiuX, XiaS, ZhangZ, et al. Channelling inflammation: gasdermins in physiology and disease[J]. Nat Rev Drug Discov, 2021,20(5):384-405. DOI: 10.1038/s41573-021-00154-z. [30] PastarI, SawayaAP, MarjanovicJ, et al. Intracellular Staphylococcus aureus triggers pyroptosis and contributes to inhibition of healing due to perforin-2 suppression[J]. J Clin Invest, 2021,131(24):e133727. DOI: 10.1172/JCI133727. [31] AoX, YanH, HuangM, et al. Lavender essential oil accelerates lipopolysaccharide-induced chronic wound healing by inhibiting caspase-11-mediated macrophage pyroptosis[J]. Kaohsiung J Med Sci, 2023,39(5):511-521. DOI: 10.1002/kjm2.12654. [32] LiY, TuZ, ChenF, et al. Anti-inflammatory effect of Danhong injection through inhibition of GSDMD-mediated pyroptosis[J]. Phytomedicine, 2023,113:154743. DOI: 10.1016/j.phymed.2023.154743. [33] 欧泽林, 王珏, 时荣, 等. 负载焦亡抑制剂的活性氧响应性自组装纳米胶束对糖尿病大鼠全层皮肤缺损的影响[J]. 中华烧伤与创面修复杂志,2023,39(1):35-44.DOI: 1z0.3760/cma.j.cn501225-20221109-00483. [34] ZhongY, LuY, YangX, et al. The roles of NLRP3 inflammasome in bacterial infection[J]. Mol Immunol, 2020,122:80-88. DOI: 10.1016/j.molimm.2020.03.020. [35] VinaikR, AbdullahiA, BarayanD, et al. NLRP3 inflammasome activity is required for wound healing after burns[J]. Transl Res, 2020,217:47-60. DOI: 10.1016/j.trsl.2019.11.002. [36] WangX, BlancoLP, Carmona-RiveraC, et al. Effects of gasdermin D in modulating murine lupus and its associated organ damage[J]. Arthritis Rheumatol, 2020,72(12):2118-2129. DOI: 10.1002/art.41444. [37] LammertCR, FrostEL, BellingerCE, et al. AIM2 inflammasome surveillance of DNA damage shapes neurodevelopment[J]. Nature, 2020,580(7805):647-652. DOI: 10.1038/s41586-020-2174-3. -
图 1 炎症期糖尿病创面中细胞焦亡的作用机制
注：IL为白细胞介素,pro-IL为IL前体,NLRP3为核苷酸结合寡聚化结构域样受体蛋白3,caspase为胱天蛋白酶,pro-caspase为caspase前体,TXNIP为硫氧还蛋白相互作用蛋白；图中黑色箭头表示促进,蓝色箭头表示剪切,绿色箭头表示寡聚化
-
下载:
图(2)
计量
- 文章访问数: 133
- HTML全文浏览量: 26
- PDF下载量: 12
- 被引次数: 0
