切换至 "中华医学电子期刊资源库"

中华普通外科学文献(电子版) ›› 2024, Vol. 18 ›› Issue (04) : 300 -304. doi: 10.3877/cma.j.issn.1674-0793.2024.04.013

综述

NLRP3炎性小体在急性胰腺炎中作用的研究进展
李嘉兴1, 孙乙文1, 李文星1,()   
  1. 1. 030001 太原,山西医科大学第二医院普通外科
  • 收稿日期:2023-11-10 出版日期:2024-08-01
  • 通信作者: 李文星
  • 基金资助:
    山西省自然科学研究面上项目(20210302123261)

Advances in the role of NLRP3 inflammasome in acute pancreatitis

Jiaxing Li1, Yiwen Sun1, Wenxing Li1,()   

  1. 1. Department of General Surgery, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China
  • Received:2023-11-10 Published:2024-08-01
  • Corresponding author: Wenxing Li
引用本文:

李嘉兴, 孙乙文, 李文星. NLRP3炎性小体在急性胰腺炎中作用的研究进展[J/OL]. 中华普通外科学文献(电子版), 2024, 18(04): 300-304.

Jiaxing Li, Yiwen Sun, Wenxing Li. Advances in the role of NLRP3 inflammasome in acute pancreatitis[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2024, 18(04): 300-304.

急性胰腺炎是一种与炎性反应密切相关的消化系统疾病。NOD样受体蛋白3 (NLRP3)炎性小体是一种蛋白质复合物,在炎症风暴发生、炎性状态的调节中起着至关重要的作用,其通过激活氧化应激、调节肠道菌群和驱动细胞焦亡等,影响急性胰腺炎的发生、发展和结局转归,有望成为急性胰腺炎诊断的生物标志物及治疗新靶点。现就NLRP3炎性小体与急性胰腺炎的关系以及其相互影响机制的研究现状作一综述。

Acute pancreatitis (AP) is a gastrointestinal disease closely associated with inflammatory response. The NLRP3 inflammasome is a protein complex, which plays a crucial role in the development of inflammatory storms and the regulation of inflammatory states. NLRP3 inflammasome affects the occurrence, development and outcome of AP by activating oxidative stress, regulating intestinal flora and driving cellular pyroptosis, and it is expected to become a biomarker and therapeutic target for the diagnosis of AP. The current state of research on the relationship between NLRP3 inflammasome and AP and the mechanism of their interaction are summarized.

图1 NLRP3炎性小体的经典途径、非经典途径和替代途径 NLRP3包含三个主要结构:中心核苷酸结合域、富含亮氨酸重复序列和Pyrin结构域。经典途径(左)是由TLRs受体识别PAMPs/DAMPs(包括LSP、ATP、微生物毒素、细菌表面组分和活性氧等),介导NF-κB相关信号通路,激活NLRP3炎性小体。非经典途径(中)是由革兰阴性菌的LPS启动,被小鼠的caspase-11或人的caspase-4/5识别,裂解GSDMD,激活NLRP3炎性小体。替代途径(右)仅存在于人单核细胞中,LPS被TLR4识别,通过caspase-8/FADD/RIPK3信号通路激活NLRP3炎性小体。NLRP3炎性小体通过裁剪pro-IL-1和pro-IL-18,或启动焦亡促进IL-1、IL-18释放,使细胞外IL-1、IL-18表达上调。LPS:脂多糖;PAMPs/DAMPs:病原体相关分子模式或危险相关分子模式;TLRs:Toll样受体;TLR4:Toll样受体4;ASC:凋亡相关斑点样蛋白
[1]
Lee DW, Cho CM. Predicting severity of acute pancreatitis[J]. Medicina (Kaunas), 2022, 58(6): 787.
[2]
Voronina S, Chvanov M, De Faveri F, et al. Autophagy, acute pancreatitis and the metamorphoses of a trypsinogen-activating organelle[J]. Cells, 2022, 11(16): 2514.
[3]
陈亮, 杨硕菲, 薛冠华. NLRP3炎症小体与血栓形成的关系研究进展[J]. 中华普通外科杂志, 2023, 38(9) : 710-713.
[4]
Liu T, Wang Q, Du Z, et al. The trigger for pancreatic disease: NLRP3 inflammasome[J]. Cell Death Discov, 2023, 9(1): 246.
[5]
Kelley N, Jeltema D, Duan Y, et al. The NLRP3 inflammasome: An overview of mechanisms of activation and regulation[J]. Int J Mol Sci, 2019, 20(13): 3328.
[6]
Qiang R, Li Y, Dai X, et al. NLRP3 inflammasome in digestive diseases: from mechanism to therapy[J]. Front Immunol, 2022, 13: 978190.
[7]
Zhao N, Li CC, Di B, et al. Recent advances in the NEK7-licensed NLRP3 inflammasome activation: mechanisms, role in diseases and related inhibitors[J]. J Autoimmun, 2020, 113: 102515.
[8]
Que X, Zheng S, Song Q, et al. Fantastic voyage: the journey of NLRP3 inflammasome activation[J]. Genes Dis, 2024, 11(2): 819-829.
[9]
Chen Z, Zhang M, Zhao Y, et al. Hydrogen sulfide contributes to uterine quiescence through inhibition of NLRP3 inflammasome activation by suppressing the TLR4/NF-κB signalling pathway[J]. J Inflamm Res, 2021, 14: 2753-2768.
[10]
Shen Y, Yang H, Wu D, et al. NLRP3 inflammasome inhibitor MCC950 can reduce the damage of pancreatic and intestinal barrier function in mice with acute pancreatitis[J]. Acta Cir Bras, 2022, 37(7): e370706.
[11]
Chu LH, Indramohan M, Ratsimandresy RA, et al. The oxidized phospholipid oxPAPC protects from septic shock by targeting the non-canonical inflammasome in macrophages[J]. Nat Commun, 2018, 9(1): 996.
[12]
Hussain T, Murtaza G, Metwally E, et al. The role of oxidative stress and antioxidant balance in pregnancy[J]. Mediators Inflamm, 2021, 2021: 9962860.
[13]
Gong C, Yang H, Wang S, et al. hTERT promotes CRC proliferation and migration by recruiting YBX1 to increase NRF2 expression[J]. Front Cell Dev Biol, 2021, 9: 658101.
[14]
Kong L, Zhang H, Lu C, et al. AICAR, an AMP-activated protein kinase activator, ameliorates acute pancreatitis-associated liver injury partially through Nrf2-mediated antioxidant effects and inhibition of NLRP3 inflammasome activation[J]. Front Pharmacol, 2021, 12: 724514.
[15]
Xiang H, Guo F, Tao X, et al. Pancreatic ductal deletion of S100A9 alleviates acute pancreatitis by targeting VNN1-mediated ROS release to inhibit NLRP3 activation[J]. Theranostics, 2021, 11(9): 4467-4482.
[16]
Kim ER, Kim SR, Cho W, et al. Short term isocaloric ketogenic diet modulates NLRP3 inflammasome via B-hydroxybutyrate and fibroblast growth factor 21[J]. Front Immunol, 2022, 13: 843520.
[17]
Li XY, He C, Zhu Y, et al. Role of gut microbiota on intestinal barrier function in acute pancreatitis[J]. World J Gastroenterol, 2020, 26(18): 2187-2193.
[18]
Jia L, Chen H, Yang J, et al. Combinatory antibiotic treatment protects against experimental acute pancreatitis by suppressing gut bacterial translocation to pancreas and inhibiting NLRP3 inflammasome pathway[J]. Innate Immun, 2020, 26(1): 48-61.
[19]
Ferrero-Andrés A, Panisello-Roselló A, Roselló-Catafau J, et al. NLRP3 inflammasome-mediated inflammation in acute pancreatitis[J]. Int J Mol Sci, 2020, 21(15): 5386.
[20]
Li H, Xie J, Guo X, et al. Bifidobacterium spp. and their metabolite lactate protect against acute pancreatitis via inhibition of pancreatic and systemic inflammatory responses[J]. Gut Microbes, 2022, 14(1): 2127456.
[21]
Li X, He C, Li N, et al. The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice[J]. Gut Microbes, 2020, 11(6): 1774-1789.
[22]
Quiroga R, Nistal E, Estébanez B, et al. Exercise training modulates the gut microbiota profile and impairs inflammatory signaling pathways in obese children[J]. Exp Mol Med, 2020, 52(7): 1048-1061.
[23]
Coll RC, Schroder K, Pelegrín P. NLRP3 and pyroptosis blockers for treating inflammatory diseases[J]. Trends Pharmacol Sci, 2022, 43(8): 653-668.
[24]
Wu X, Yao J, Hu Q, et al. Emodin ameliorates acute pancreatitis-associated lung injury through inhibiting the alveolar macrophages pyroptosis[J]. Front Pharmacol, 2022, 13: 873053.
[25]
Wu XB, Sun HY, Luo ZL, et al. Plasma-derived exosomes contribute to pancreatitis-associated lung injury by triggering NLRP3-dependent pyroptosis in alveolar macrophages[J]. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(5): 165685.
[26]
Sun B, Chen Z, Chi Q, et al. Endogenous tRNA-derived small RNA (tRF3-Thr-AGT) inhibits ZBP1/NLRP3 pathway-mediated cell pyroptosis to attenuate acute pancreatitis (AP)[J]. J Cell Mol Med, 2021, 25(22): 10441-10453.
[27]
Zhang Q, Tao X, Xia S, et al. Emodin attenuated severe acute pancreatitis via the P2X ligand-gated ion channel 7/NOD-like receptor protein 3 signaling pathway[J]. Oncol Rep, 2019, 41(1): 270-278.
[28]
Jiang N, Li Z, Luo Y, et al. Emodin ameliorates acute pancreatitis-induced lung injury by suppressing NLRP3 inflammasome-mediated neutrophil recruitment[J]. Exp Ther Med, 2021, 22(2): 857.
[29]
Xu Q, Wang M, Guo H, et al. Emodin alleviates severe acute pancreatitis-associated acute lung injury by inhibiting the cold-inducible rna-binding protein (CIRP)-mediated activation of the NLRP3/IL-1β/CXCL1 signaling[J]. Front Pharmacol, 2021, 12: 655372.
[1] 陆婷, 范晴敏, 王洁, 万晓静, 许春芳, 董凤林. 超声引导下经皮穿刺置管引流对重症急性胰腺炎的疗效及应用时机的选择[J/OL]. 中华医学超声杂志(电子版), 2024, 21(05): 511-516.
[2] 黄蓉, 梁自毓, 祁文瑾. NLRP3炎症小体在胎膜早破孕妇血清中的表达及其意义[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 540-548.
[3] 戴睿, 张亮, 陈浏阳, 张永博, 吴丕根, 孙华, 杨盛, 孟博. 肠道菌群与椎间盘退行性变相关性的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(06): 546-549.
[4] 张洁, 罗小霞, 余鸿. 系统性免疫炎症指数对急性胰腺炎患者并发器官功能损伤的预测价值[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 68-71.
[5] 李玲, 刘亚, 李培玲, 张秀敏, 李萍. 直肠癌患者术后肠道菌群的变化与抑郁症相关性研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 607-610.
[6] 党军强, 杨雁灵, 汪庆强, 尚琳, 朱磊, 项红军. 主动经皮穿刺引流治疗重症急性胰腺炎并发急性坏死物积聚的疗效分析[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 671-674.
[7] 蔡艺丹, 方坚, 张志强, 陈莉, 张世安, 夏磊, 阮梅, 李东良. 经颈静脉肝内门体分流术对肝硬化门脉高压患者肠道菌群及肝功能的影响[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(05): 285-293.
[8] 杜霞, 马梦青, 曹长春. 造影剂诱导的急性肾损伤的发病机制及干预靶点研究进展[J/OL]. 中华肾病研究电子杂志, 2024, 13(05): 279-282.
[9] 史清泉, 苗彬, 王烁, 陶琳, 沈晨. miR-181a-5p 靶向ATG5 抑制雨蛙素诱导的大鼠胰腺腺泡细胞AR42J自噬的机制研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 524-530.
[10] 曾明芬, 王艳. 急性胰腺炎合并脂肪肝患者CT 与彩色多普勒超声诊断参数与其病情和预后的关联性研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 531-535.
[11] 沈炎, 张俊峰, 唐春芳. 预后营养指数结合血清降钙素原、胱抑素C及视黄醇结合蛋白对急性胰腺炎并发急性肾损伤的预测价值[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 536-540.
[12] 杨爽, 余宏亮, 谢敏. CT 与超声检查对急性胰腺炎合并脂肪肝的诊断价值[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 541-544.
[13] 丛黎, 马林, 陈旭, 李文文, 张亮亮, 周华亭. 改良CT严重指数联合炎症指标在重症急性胰腺炎患者胰腺感染预测及预后评估中的研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(05): 432-436.
[14] 宋燕秋, 戚桂艳, 杨双双, 周萍. 重症急性胰腺炎肠道菌群特征及早期肠内营养联合微生态制剂治疗的临床价值[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(05): 442-447.
[15] 丁洪基, 赵长江, 孙鹏飞, 王灿, 王贵珍, 李龙龙. 细胞焦亡与疾病的关系研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(07): 682-686.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?