脓毒症动物模型的制备方法及影响因素

doi:10.12300/j.issn.1674-5817.2021.121

实验动物与比较医学 ›› 2022, Vol. 42 ›› Issue (3): 207-212.DOI: 10.12300/j.issn.1674-5817.2021.121

脓毒症动物模型的制备方法及影响因素

李潇(), 颜海鹏, 肖政辉()()

南华大学儿科学院, 湖南省儿童医院重症医学科, 长沙 410007

收稿日期:2021-07-19 修回日期:2021-11-22 出版日期:2022-06-25 发布日期:2022-07-01
通讯作者: 肖政辉（1967—），女，博士，教授，主要从事儿童急救医学研究， E-mail： xiaozh888@126.com。ORCID： 0000-0003-2056-8798
作者简介:李潇（1996—），女，硕士研究生，主要从事儿童急救医学研究， E-mail： lixiaost@163.com
基金资助:
湖南省重点实验室和工程技术研究中心组建项目：儿童急救医学湖南省重点实验室(2018TP1028。湖南省科技创新重大项目：湖南省急危重症急救能力提升与突发公共卫生应急救治关键技术协同创新工程-创伤后脓毒症、休克的早期预警、诊疗能力提升及关键技术研究2020SK1014-3。湖南省儿童医院院级课题2019C38)

Construction Methods and Influencing Factors on Animal Model of Sepsis

Xiao LI(), Haipeng YAN, Zhenghui XIAO()()

Academy of Pediatrics of University of South China, Department of Pediatric Intensive Care Unit of Hunan Children's Hospital, Changsha 410007, China

Received:2021-07-19 Revised:2021-11-22 Published:2022-06-25 Online:2022-07-01
Contact: XIAO Zhenghui (ORCID: 0000-0003-2056-8798), E-mail: xiaozh888@126.com

摘要/Abstract

摘要：

脓毒症是常见的急危重症，其致病机制复杂，常涉及全身多个器官、系统，其中炎性反应、免疫功能紊乱、凝血功能障碍等多种因素联结成相互联系、相互影响的网络系统，加重病情进展。目前脓毒症病死率约25%，严重威胁人类健康。建立稳定可靠的脓毒症实验动物模型是了解感染早期宿主防御调控机制、病情进展期宿主反应失调机制及研究新型药物治疗效果的重要手段。目前脓毒症动物模型的建立方法种类繁多，且影响因素较多。本文就脓毒症动物模型的制备方法及影响因素进行综述，以期为研究者选择合适的动物模型提供参考。

关键词: 脓毒症, 动物模型, 盲肠结扎穿孔术, 小鼠

Abstract:

Sepsis is a common acute and critical illness, and its pathogenic mechanism is complex, often involving multiple organs and systems in the body. Various factors such as inflammatory response, immune dysfunction, and coagulation dysfunction are connected into an interconnected and mutually influencing network system, aggravating the severity of the disease. At present, the case fatality rate of sepsis is about 25%, which is a serious threat to human health. Establishing a stable and reliable experimental animal model of sepsis is an important means to understand the mechanism of host defense regulation in the early stage of infection, the mechanism of host response disorder in the stage of disease progression and to study the therapeutic effect of new therapeutic drugs. At present, there are many methods to establish animal models of sepsis, and there are many influencing factors. Therefore, this paper reviewed the preparation methods and influencing factors of animal models of sepsis, in order to provide some references for researchers to select suitable animal models.

Key words: Sepsis, Animal models, Cecal ligation and puncture, Mice

中图分类号:

R-332

李潇, 颜海鹏, 肖政辉. 脓毒症动物模型的制备方法及影响因素[J]. 实验动物与比较医学, 2022, 42(3): 207-212.

Xiao LI, Haipeng YAN, Zhenghui XIAO. Construction Methods and Influencing Factors on Animal Model of Sepsis[J]. Laboratory Animal and Comparative Medicine, 2022, 42(3): 207-212.

参考文献 38

1	FERNANDO S M, REARDON P M, ROCHWERG B, et al. Sepsis-3 septic shock criteria and associated mortality among infected hospitalized patients assessed by a rapid response team[J]. Chest, 2018, 154(2):309-316. DOI:10.1016/j.chest.2018.05.004 .
2	FLEISCHMANN C, SCHERAG A, ADHIKARI N K, et al. Assessment of global incidence and mortality of hospital-treated Sepsis. current estimates and limitations[J]. Am J Respir Crit Care Med, 2016, 193(3):259-272. DOI:10.1164/rccm.201504-0781oc .
3	江伟, 杜斌. 中国脓毒症流行病学现状[J]. 医学研究生学报, 2019, 32(1):5-8. DOI:10.16571/j.cnki.1008-8199.2019.01.002 .
	JIANG W, DU B. Epidemiology of sepsis in China[J]. J Med Postgrad, 2019, 32(1):5-8. DOI:10.16571/j.cnki.1008-8199.2019.01.002 .
4	TAVEIRA DA SILVA A M, KAULBACH H C, CHUIDIAN F S, et al. Brief report: shock and multiple-organ dysfunction after self-administration of Salmonella endotoxin[J]. N Engl J Med, 1993, 328(20):1457-1460. DOI:10.1056/nejm199305203282005 .
5	KORNEEV K V. Mouse models of Sepsis and septic shock[J]. Mol Biol, 2019, 53(5):704-717. DOI:10.1134/S0026893319050108 .
6	KINGSLEY S M K, BHAT B V. Differential paradigms in animal models of Sepsis [J]. Curr Infect Dis Rep, 2016, 18(9):26. DOI:10.1007/s11908-016-0535-8 .
7	CARPENTER K C, HAKENJOS J M, FRY C D, et al. The influence of pain and analgesia in rodent models of Sepsis [J]. Comp Med, 2019, 69(6):546-554. DOI:10.30802/aalas-cm-19-000004 .
8	MISHRA S K, CHOUDHURY S. Experimental protocol for cecal ligation and puncture model of polymicrobial Sepsis and assessment of vascular functions in mice[J]. Methods Mol Biol, 2018, 1717:161-187. DOI:10.1007/978-1-4939-7526-6_14 .
9	BURAS J A, HOLZMANN B, SITKOVSKY M. Animal Models of sepsis: setting the stage[J]. Nat Rev Drug Discov, 2005, 4(10):854-865. DOI:10.1038/nrd1854 .
10	MURANDO F, PELOSO A, COBIANCHI L. Experimental abdominal Sepsis: sticking to an awkward but still useful translational model[J]. Mediat Inflamm, 2019, 2019:8971036. DOI:10.1155/2019/8971036 .
11	NICOLAI O, PÖTSCHKE C, SCHMOECKEL K, et al. Antibody production in murine polymicrobial Sepsis—kinetics and key players[J]. Front Immunol, 2020, 11:828. DOI:10.3389/fimmu.2020.00828 .
12	ZANTL N, UEBE A, NEUMANN B, et al. Essential role of gamma interferon in survival of colon ascendens stent peritonitis, a novel murine model of abdominal sepsis[J]. Infect Immun, 1998, 66(5):2300-2309. DOI:10.1128/IAI.66.5. 2300-2309.1998 .
13	RINCON J C, EFRON P A, MOLDAWER L L, et al. Cecal slurry injection in neonatal and adult mice[J]. Methods Mol Biol, 2021, 2321:27-41. DOI:10.1007/978-1-0716-1488-4_4 .
14	LEWIS A J, SEYMOUR C W, ROSENGART M R. Current murine models of Sepsis [J]. Surg Infect, 2016, 17(4):385-393. DOI:10.1089/sur.2016.021 .
15	NAKAJIMA R, HAGIHARA H, MIYAKAWA T. Similarities of developmental gene expression changes in the brain between human and experimental animals: rhesus monkey, mouse, Zebrafish, and Drosophila [J]. Mol Brain, 2021, 14(1):135. DOI:10.1186/s13041-021-00840-4 .
16	BURAS J A, HOLZMANN B, SITKOVSKY M. Animal Models of sepsis: setting the stage[J]. Nat Rev Drug Discov, 2005, 4(10):854-865. DOI:10.1038/nrd1854 .
17	ZINGARELLI B, COOPERSMITH C M, DRECHSLER S, et al. Part I: Minimum quality threshold in preclinical sepsis studies (MQTiPSS) for study design and humane modeling endpoints[J]. Shock, 2019, 51(1):10-22. DOI:10.1097/SHK. 0000000000001243 .
18	RAYMOND S L, LÓPEZ M C, BAKER H V, et al. Unique transcriptomic response to sepsis is observed among patients of different age groups[J]. PLoS One, 2017, 12(9): e0184159. DOI:10.1371/journal.pone.0184159 .[PubMed]
19	STORTZ J A, HOLLEN M K, NACIONALES D C, et al. Old mice demonstrate organ dysfunction as well as prolonged inflammation, immunosuppression, and weight loss in a modified surgical Sepsis model[J]. Crit Care Med, 2019, 47(11): e919-e929. DOI:10.1097/CCM.0000000000003926 .[PubMed]
20	TURNBULL I R, WLZOREK J J, OSBORNE D, et al. Effects of age on mortality and antibiotic efficacy in cecal ligation and puncture[J]. Shock Augusta Ga, 2003, 19(4):310-313. DOI:10.1097/00024382-200304000-00003 .
21	Xu J, Tong L, YAO J, et al. Association of sex with clinical outcome in critically Ill sepsis patients: A retrospective analysis of the large clinical database MIMIC-III[J]. Shock, 2019 52(2):146-151. DOI:10.1097/SHK.0000000000001253 .
22	MEGE J L, BRETELLE F, LEONE M. Sex and bacterial infectious diseases[J]. New Microbes New Infect, 2018, 26: S100-S103. DOI:10.1016/j.nmni.2018.05.010 .
23	GAY L, MELENOTTE C, LAKBAR I, et al. Sexual dimorphism and gender in infectious diseases[J]. Front Immunol, 2021, 12:698121. DOI:10.3389/fimmu.2021.698121 .
24	LEFÈVRE N, CORAZZA F, VALSAMIS J, et al. The number of X chromosomes influences inflammatory cytokine production following toll-like receptor stimulation[J]. Front Immunol, 2019, 10:1052. DOI:10.3389/fimmu.2019.01052 .
25	Knöferl M W, Angele M K, DIODATO M D, et al. Female sex hormones regulate macrophage function after trauma-hemorrhage and prevent increased death rate from subsequent sepsis[J]. Ann Surg, 2002, 235(1):105-112. DOI:10.1097/00000658-200201000-00014 .
26	HELLMAN J, BAHRAMI S, BOROS M, et al. Part Ⅲ: Minimum quality threshold in preclinical sepsis studies (MQTiPSS) for fluid resuscitation and antimicrobial therapy endpoints[J]. Shock, 2019, 51(1):33-43. DOI:10.1097/SHK.0000000000001209 .
27	BYRNE L, HAREN F VAN. Fluid resuscitation in human sepsis: time to rewrite history? [J]. Ann Intensive Care, 2017, 7(1):4. DOI:10.1186/s13613-016-0231-8 .
28	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. DOI:10.1007/s00134-021-06506-y .
29	ESMON C T. Why do animal models (sometimes) fail to mimic human sepsis?[J]. Crit Care Med, 2004, 32(5 ): S219-S222. DOI:10.1097/01.ccm.0000127036.27343.48 .
30	CARPENTER K C, HAKENJOS J M, FRY C D, et al. The influence of pain and analgesia in rodent models of Sepsis [J]. Comp Med, 2019, 69(6):546-554. DOI:10.30802/aalas-cm-19-000004 .
31	LEE H T, EMALA C W, JOO J D, et al. Isoflurane improves survival and protects against renal and hepatic injury in murine septic peritonitis[J]. Shock, 2007, 27(4):373-379. DOI:10.1097/01.shk.0000248595.17130.24 .
32	HERRMANN I K, CASTELLON M, SCHWARTZ D E, et al. Volatile anesthetics improve survival after cecal ligation and puncture[J]. Anesthesiology, 2013, 119(4):901-906. DOI:10.1097/aln.0b013e3182a2a38c .
33	BAXTER M G, MURPHY K L, TAYLOR P M, et al. Chloral hydrate is not acceptable for anesthesia or euthanasia of small animals[J]. Anesthesiology, 2009, 111(1):209; author reply 209-209; author reply 210. DOI:10.1097/ALN.0b013e3181a8617e .
34	SINGLETON K D, WISCHMEYER P E. Distance of cecum ligated influences mortality, tumor necrosis factor-alpha and interleukin-6 expression following cecal ligation and puncture in the rat[J]. Eur Surg Res, 2003, 35(6):486-491. DOI:10.1159/000073387 .
35	SONG T Z, YIN H L, CHEN J T, et al. Survival advantage depends on cecal volume rather than cecal length in a mouse model of cecal ligation and puncture[J]. J Surg Res, 2016, 203(2):476-482. DOI:10.1016/j.jss.2016.03.019 .
36	DEJAGER L, PINHEIRO I, DEJONCKHEERE E, et al. Cecal ligation and puncture: the gold standard model for polymicrobial sepsis? [J]. Trends Microbiol, 2011, 19(4):198-208. DOI:10.1016/j.tim.2011.01.001 .
37	CAVAILLON J M, SINGER M, SKIRECKI T. Sepsis therapies: learning from 30 years of failure of translational research to propose new leads[J]. EMBO Mol Med, 2020, 12(4): e10128. DOI:10.15252/emmm.201810128 .
38	ALVERDY J C, KESKEY R, THEWISSEN R. Can the cecal ligation and puncture model Be repurposed to better inform therapy in human Sepsis? [J]. Infect Immun, 2020, 88(9): e00942-e00919. DOI:10.1128/iai.00942-19 .

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脓毒症动物模型的制备方法及影响因素

Construction Methods and Influencing Factors on Animal Model of Sepsis

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