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中华危重症医学杂志(电子版) ›› 2024, Vol. 17 ›› Issue (02) : 155 -163. doi: 10.3877/cma.j.issn.1674-6880.2024.02.012

综述

脓毒症治疗药物的研究进展
高芮1, 马晓媛1, 梁华平1, 王芳杰1,()   
  1. 1. 400042 重庆,陆军特色医学中心战伤感染与特需药品研究室
  • 收稿日期:2023-02-14 出版日期:2024-04-30
  • 通信作者: 王芳杰
  • 基金资助:
    重庆市自然科学基金面上项目(cstc2020jcyj-msxmX0510); 重庆市博士直通车科研项目(CSTB2022BSXM-JCX0024)
  • Received:2023-02-14 Published:2024-04-30
引用本文:

高芮, 马晓媛, 梁华平, 王芳杰. 脓毒症治疗药物的研究进展[J]. 中华危重症医学杂志(电子版), 2024, 17(02): 155-163.

脓毒症是由感染引起宿主反应失调从而导致危及生命的多器官功能障碍,常并发于外科大手术、烧伤、创伤及其他重症疾病等,具有较高的发病率和病死率。根据世界卫生组织统计,每年脓毒症的全球死亡病例约为600万例[1]。目前临床上虽然有各种脓毒症治疗策略,但仍然没有具体、可靠的针对性治疗药物[2],因此开发此类药物是保障人类健康的迫切需要。

1
Improving the prevention, diagnosis and clinical management of sepsis[EB/OL]. (2017-05-29). [2022-09-19].

URL    
2
Zhang YY, Ning BT. Signaling pathways and intervention therapies in sepsis[J]. Signal Transduct Target Ther, 2021, 6 (1): 407.
3
Xu Z, Liu A, Yang L, et al. Changes in immune function and immunomodulatory treatments of septic patients[J]. Clin Immunol, 2022 (239): 109040.
4
Chan JK, Roth J, Oppenheim JJ, et al. Alarmins: awaiting a clinical response[J]. J Clin Invest, 2012, 122 (8): 2711-2719.
5
Karasu E, Nilsson B, Kohl J, et al. Targeting complement pathways in polytrauma- and sepsis-induced multiple-organ dysfunction[J]. Front Immunol, 2019 (10): 543.
6
Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy[J]. Nat Rev Immunol, 2013, 13 (12): 862-874.
7
Hotchkiss RS, Monneret G, Payen D. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach[J]. Lancet Infect Dis, 2013, 13 (3): 260-268.
8
Iba T, Levy JH. Inflammation and thrombosis: roles of neutrophils, platelets and endothelial cells and their interactions in thrombus formation during sepsis[J]. J Thromb Haemost, 2018, 16 (2): 231-241.
9
常泽楠,温仕宏,张义楠,等.脓毒症中内皮细胞高通透性的机制研究进展[J/CD].中华危重症医学杂志(电子版)202215(4):337-342.
10
Ito T, Kakuuchi M, Maruyama I. Endotheliopathy in septic conditions: mechanistic insight into intravascular coagulation[J]. Crit Care, 2021, 25 (1): 95.
11
Giustozzi M, Ehrlinder H, Bongiovanni D, et al. Coagulopathy and sepsis: pathophysiology, clinical manifestations and treatment[J]. Blood Rev, 2021 (50): 100864.
12
Jiao Y, Zhang T, Zhang C, et al. Exosomal miR-30d-5p of neutrophils induces M1 macrophage polarization and primes macrophage pyroptosis in sepsis-related acute lung injury[J]. Crit Care, 2021, 25 (1): 356.
13
Marshall JC. Why have clinical trials in sepsis failed?[J]. Trends Mol Med, 2014, 20 (4): 195-203.
14
Kotsaki A, Giamarellos-Bourboulis EJ. Emerging drugs for the treatment of sepsis[J]. Expert Opin Emerg Drugs, 2012, 17 (3): 379-391.
15
Panacek EA, Marshall JC, Albertson TE, et al. Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab')2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels[J]. Crit Care Med, 2004, 32 (11): 2173-2182.
16
Rice TW, Wheeler AP, Morris PE, et al. Safety and efficacy of affinity-purified, anti-tumor necrosis factor-alpha, ovine fab for injection (CytoFab) in severe sepsis[J]. Crit Care Med, 2006, 34 (9): 2271-2281.
17
Zhang Y, Liang X, Bao X, et al. Toll-like receptor 4 (TLR4) inhibitors: current research and prospective[J]. Eur J Med Chem, 2022 (235): 114291.
18
Opal SM, Laterre PF, Francois B, et al. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial[J]. JAMA, 2013, 309 (11): 1154-1162.
19
Sha T, Iizawa Y, Ii M. Combination of imipenem and TAK-242, a Toll-like receptor 4 signal transduction inhibitor, improves survival in a murine model of polymicrobial sepsis[J]. Shock, 2011, 35 (2): 205-209.
20
Ono Y, Maejima Y, Saito M, et al. TAK-242, a specific inhibitor of Toll-like receptor 4 signalling, prevents endotoxemia-induced skeletal muscle wasting in mice[J]. Sci Rep, 2020, 10 (1): 694.
21
Darden DB, Kelly LS, Fenner BP, et al. Dysregulated immunity and immunotherapy after sepsis[J]. J Clin Med, 2021, 10 (8): 1742.
22
Moriyama K, Nishida O. Targeting cytokines, pathogen-associated molecular patterns, and damage-associated molecular patterns in sepsis via blood purification[J]. Int J Mol Sci, 2021, 22 (16): 8882.
23
Cutuli SL, Artigas A, Fumagalli R, et al. Polymyxin-B hemoperfusion in septic patients: analysis of a multicenter registry[J]. Ann Intensive Care, 2016, 6 (1): 77.
24
Nemoto H, Nakamoto H, Okada H, et al. Newly developed immobilized polymyxin B fibers improve the survival of patients with sepsis[J]. Blood Purif, 2001, 19 (4): 361-368; discussion 368-369.
25
Li Bassi G, Marti JD, Xiol EA, et al. The effects of direct hemoperfusion using a polymyxin B-immobilized column in a pig model of severe Pseudomonas aeruginosa pneumonia[J]. Ann Intensive Care, 2016, 6 (1): 58.
26
Iwagami M, Yasunaga H, Doi K, et al. Postoperative polymyxin B hemoperfusion and mortality in patients with abdominal septic shock: a propensity-matched analysis[J]. Crit Care Med, 2014, 42 (5): 1187-1193.
27
Mitaka C, Tomita M. Polymyxin B-immobilized fiber column hemoperfusion therapy for septic shock[J]. Shock, 2011, 36 (4): 332-338.
28
Xia D, Wang S, Yao R, et al. Pyroptosis in sepsis: comprehensive analysis of research hotspots and core genes in 2022[J]. Front Mol Biosci, 2022 (9): 955991.
29
Pan S, Lv Z, Wang R, et al. Sepsis-induced brain dysfunction: pathogenesis, diagnosis, and treatment[J]. Oxid Med Cell Longev, 2022 (2022): 1328729.
30
Xu XE, Liu L, Wang YC, et al. Caspase-1 inhibitor exerts brain-protective effects against sepsis-associated encephalopathy and cognitive impairments in a mouse model of sepsis[J]. Brain Behav Immun, 2019 (80): 859-870.
31
Keshari RS, Silasi R, Popescu NI, et al. Inhibition of complement C5 protects against organ failure and reduces mortality in a baboon model of Escherichia coli sepsis[J]. Proc Natl Acad Sci U S A, 2017, 114 (31): E6390-E6399.
32
Martín-Fernández M, Tamayo-Velasco A, Aller R, et al. Endothelial dysfunction and neutrophil degranulation as central events in sepsis physiopathology[J]. Int J Mol Sci, 2021, 22 (12): 6272.
33
Mahajan A, Gruneboom A, Petru L, et al. Frontline science: aggregated neutrophil extracellular traps prevent inflammation on the neutrophil-rich ocular surface[J]. J Leukoc Biol, 2019, 105 (6): 1087-1098.
34
Hamam HJ, Palaniyar N. Post-translational modifications in NETosis and NETs-mediated diseases[J]. Biomolecules, 2019, 9 (8): 369.
35
Colón DF, Wanderley CW, Franchin M, et al. Neutrophil extracellular traps (NETs) exacerbate severity of infant sepsis[J]. Crit Care, 2019, 23 (1): 113.
36
Gollomp K, Kim M, Johnston I, et al. Neutrophil accumulation and NET release contribute to thrombosis in HIT[J]. JCI Insight, 2018, 3 (18): e99445.
37
Khandelwal S, Ravi J, Rauova L, et al. Polyreactive IgM initiates complement activation by PF4/heparin complexes through the classical pathway[J]. Blood, 2018, 132 (23): 2431-2440.
38
Gollomp K, Sarkar A, Harikumar S, et al. Fc-modified HIT-like monoclonal antibody as a novel treatment for sepsis[J]. Blood, 2020, 135 (10): 743-754.
39
Iba T, Levy JH, Warkentin TE, et al. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation[J]. J Thromb Haemost, 2019, 17 (11): 1989-1994.
40
Wang L, Bastarache JA, Ware LB. The coagulation cascade in sepsis[J]. Curr Pharm Des, 2008, 14 (19): 1860-1869.
41
Holder AL, Huang DT. A dream deferred: the rise and fall of recombinant activated protein C[J]. Crit Care, 2013, 17 (2): 309.
42
Levi M, Van Der Poll T. Thrombomodulin in sepsis[J]. Minerva Anestesiol, 2013, 79 (3): 294-298.
43
Yamakawa K, Murao S, Aihara M. Recombinant human soluble thrombomodulin in sepsis-induced coagulopathy: an updated systematic review and meta-analysis[J]. Thromb Haemost, 2019, 119 (1): 56-65.
44
Iba T, Gando S, Thachil J. Anticoagulant therapy for sepsis-associated disseminated intravascular coagulation: the view from Japan[J]. J Thromb Haemost, 2014, 12 (7): 1010-1019.
45
Yamakawa K, Ogura H, Fujimi S, et al. Recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis[J]. Intensive Care Med, 2013, 39 (4): 644-652.
46
Vincent JL, Ramesh MK, Ernest D, et al. A randomized, double-blind, placebo-controlled, phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation[J]. Crit Care Med, 2013, 41 (9): 2069-2079.
47
Grammatis AL, Georgiou EX, Becker CM. Pentoxifylline for the treatment of endometriosis-associated pain and infertility[J]. Cochrane Database Syst Rev, 2021 (8): CD007677.
48
Adel M, Awad HA, Abdel-Naim AB, et al. Effects of pentoxifylline on coagulation profile and disseminated intravascular coagulation incidence in Egyptian septic neonates[J]. J Clin Pharm Ther, 2010, 35 (3): 257-265.
49
Córneo EDS, Michels M, Dal-Pizzol F. Sepsis, immunosuppression and the role of epigenetic mechanisms[J]. Expert Rev Clin Immunol, 2021, 17 (2): 169-176.
50
Venet F, Rimmelé T, Monneret G. Management of sepsis-induced immunosuppression[J]. Crit Care Clin, 2018, 34 (1): 97-106.
51
Bo L, Wang F, Zhu J, et al. Granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) for sepsis: a meta-analysis[J]. Crit Care, 2011, 15 (1): R58.
52
Liu Q, Li CS. Programmed cell death-1/programmed death-ligand 1 pathway: a new target for sepsis[J]. Chin Med J (Engl), 2017, 130 (8): 986-992.
53
Chang K, Svabek C, Vazquez-Guillamet C, et al. Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis[J]. Crit Care, 2014, 18 (1): R3.
54
Webb GJ, Hirschfield GM, Lane PJ. OX40, OX40L and autoimmunity: a comprehensive review[J]. Clin Rev Allergy Immunol, 2016, 50 (3): 312-332.
55
Unsinger J, Walton AH, Blood T, et al. Frontline science: OX40 agonistic antibody reverses immune suppression and improves survival in sepsis[J]. J Leukoc Biol, 2021, 109 (4): 697-708.
56
Kawamoto E, Masui-Ito A, Eguchi A, et al. Integrin and PD-1 ligand expression on circulating extracellular vesicles in systemic inflammatory response syndrome and sepsis[J]. Shock, 2019, 52 (1): 13-22.
57
Lu X, Yang YM, Lu YQ. Immunosenescence: a critical factor associated with organ injury after sepsis[J]. Front Immunol, 2022 (13): 917293.
58
Nguyen V, Mendelsohn A, Larrick JW. Interleukin-7 and immunosenescence[J]. J Immunol Res, 2017 (2017): 4807853.
59
Mackall CL, Fry TJ, Gress RE. Harnessing the biology of IL-7 for therapeutic application[J]. Nat Rev Immunol, 2011, 11 (5): 330-342.
60
Venet F, Foray AP, Villars-Méchin A, et al. IL-7 restores lymphocyte functions in septic patients[J]. J Immunol, 2012, 189 (10): 5073-5081.
61
Francois B, Jeannet R, Daix T, et al. Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial[J]. JCI Insight, 2018, 3 (5): e98960.
62
胡斌,刘冰,赵浩延,等.中医药治疗脓毒症的研究进展[J].中国医药指南202018(22):32-33.
63
王宜艳,陈伟.从"毒""瘀""虚"谈脓毒症的中医治疗进展[J].中国中医急症201726(9):1609-1612.
64
李建洪,龚瑞莹,吕锐萍,等.脓毒症的中医药治疗及研究概况[J].中国中医急症202130(1):185-188.
65
周雯,万建国,邬叔兵,等.大黄治疗脓毒症急性胃肠损伤的临床研究[J].江西医药202156(2):156-158.
66
陈秋莹.中药免疫调节作用及其研究进展[J].江西医药201954(2):81-184.
67
沈丽娟,吴锡平,关云艳,等.不同剂量黄芪对脓毒症患者免疫功能和血小板活化因子的干预研究[J].南京中医药大学学报201935(2):135-138.
68
杨晓玲,周强,郑春华,等.人参多糖对创伤性脓毒症患者免疫功能和细胞炎性因子的影响[J].临床合理用药杂志201811(15):66-68.
69
马伟欢,齐伟平,张成锋,等.丹红注射液对严重烧伤脓毒血症患者血浆IL-1β、MDA和SOD的影响及对急性肾损伤的保护效应[J].现代中西医结合杂志201726(25):2744-2746,2750.
70
林颜,阮树斌,陈晓东,等.丹参川芎嗪注射液对重度烧伤患者炎性因子影响及预防脓毒症发生效果分析[J].河北医学201824(3):382-385.
71
司向,管向东.参附注射液在危重症患者中的应用进展[J/CD].中华重症医学电子杂志(网络版)20206(1):92-95.
72
胡超,张谦.参附注射液改善脓毒症患者微循环的研究进展[J].中国中医急症202130(8):1501-1504.
73
王伟,秦超,卜克,等.参附注射液治疗脓毒症休克67例疗效观察[J].安徽医药202226(7):1458-1462.
74
Tian S, Qin D, Ye Y, et al. Scientific evidence of xuebijing injection in the treatment of sepsis[J]. Evid Based Complement Alternat Med, 2021 (2021): 6879278.
75
宋雪君,李文艳,符银舅,等.血必净治疗脓毒症的临床疗效及对中性粒细胞与淋巴细胞比值的影响[J].中国中西医结合急救杂志202128(6):690-692.
76
董佳倩,余丹妮,裘秀月.穴位贴敷干预小儿咳嗽变异性哮喘的临床应用概况[J].浙江中医杂志201954(9):700-701.
77
周波巧,葛婷爱,冯晓菲.四逆汤穴位贴敷治疗脓毒症胃肠功能障碍35例[J].浙江中医杂志202257(6):425,461.
78
杨博皓,林爽,马骏麒.针灸对脓毒症患者免疫功能的影响及机制研究进展[J].新疆医学202252(4):375-378.
79
李亚莉,褚玉茹,于乃浩,等.针灸改善脓毒症患者胃肠功能障碍的临床观察[J].天津中医药202138(4):479-482.
80
van der Poll T, van de Veerdonk FL, Scicluna BP, et al. The immunopathology of sepsis and potential therapeutic targets[J]. Nat Rev Immunol, 2017, 17 (7): 407-420.
81
Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021[J]. Intensive Care Med, 2021, 47 (11): 1181-1247.
82
张锦鑫,沈括,胡大海,等.脓毒症早期诊断和治疗进展[J/CD].中华损伤与修复杂志(电子版)202217(1):76-80.
83
Papafilippou L, Claxton A, Dark P, et al. Nanotools for sepsis diagnosis and treatment[J]. Adv Healthc Mater, 2021, 10 (1): e2001378.
84
Dawulieti J, Sun M, Zhao Y, et al. Treatment of severe sepsis with nanoparticulate cell-free DNA scavengers[J]. Sci Adv, 2020, 6 (22): eaay7148.
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