World Journal of Emergency Medicine ›› 2025, Vol. 16 ›› Issue (4): 321-330.doi: 10.5847/wjem.j.1920-8642.2025.082
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Open Access
Rui Li1,2,3, Jing Zhou1,2,3, Wei Huang1,2,3, Jingjing Ye1,2,3, Wei Chong4(
), Panpan Chang1,2,3(
), Tianbing Wang1,2,3(
)
Received:2024-08-09
Accepted:2024-12-28
Online:2025-07-18
Published:2025-07-01
Contact:
Wei Chong,Panpan Chang,Tianbing Wang
E-mail:wchong@cmu.edu.cn;drchang@yeah.net;wangtianbing@pkuph.edu.cn
Rui Li, Jing Zhou, Wei Huang, Jingjing Ye, Wei Chong, Panpan Chang, Tianbing Wang. Murine model for investigating severe trauma[J]. World Journal of Emergency Medicine, 2025, 16(4): 321-330.
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URL: http://wjem.com.cn/EN/10.5847/wjem.j.1920-8642.2025.082
Figure 1.
The establishement of murine model of severe trauma including: femoral fracture, abdominal soft tissue injury and hemorrhagic shock. A: external image after skin preparation; B: external image upon completion of modeling; C: X-ray image upon completion of modeling; D: external image after modeling.
Figure 4.
Severe trauma and 30% total blood volume loss induced shock in the model mice. A: early changes in mean arterial pressure (MAP); B: early changes in body temperature; C: early changes in lactate levels. Data are presented as mean ± standard error of the mean (SEM) (n=6). MAP and body temperature were compared between the two groups at each time point using repeated measures ANOVA. Lactic acid data were analyzed using one-way ANOVA followed by Dunnett’s post-hoc test to compare time points with the sham group. *P< 0.05.
Table 1.
Comparisons of blood cell counts at different time points in the model and sham groups
| Variables | Sham | Model | ||||
|---|---|---|---|---|---|---|
| 1 h | 2 h | 3 h | 6 h | 12 h | ||
| RBC, ×1012/L | 10.3±0.5 | 8.7±0.6*** | 8.4±0.5*** | 8.8±0.3*** | 9.2±0.6** | 10.4±0.5 |
| WBC, ×1012/L | 8.6±0.2 | 4.6±1.0*** | 6.1±0.7*** | 7.0±0.6*** | 8.4±0.6 | 9.0±0.5 |
| PLT, ×109/L | 827.7±69.7 | 142.0±66.7** | 292.2±193.0** | 345.8±52.4** | 525.8±132.6** | 613.0±179.1* |
Table 2.
Comparisons of blood gas analysis results at different time points in the model and sham groups
| Variables | Sham | Model | ||||
|---|---|---|---|---|---|---|
| 1 h | 2 h | 3 h | 6 h | 12 h | ||
| pH | 7.4±0.1 | 7.2±0.2* | 7.2±0.1* | 7.3±0.0 | 7.3±0.1 | 7.3±0.0 |
| BE, mmol/L | 9.1±0.2 | 11.7±2.0* | 8.8±1.4 | 10.0±1.1 | 9.0±1.6 | 9.0±1.7 |
| HCO3-, mmol/L | 17.3±0.8 | 14.5±1.8* | 17.2±1.3 | 17.1±1.2 | 16.1±2.3 | 16.7±0.8 |
| PaO2, mmHg | 120.3±11.7 | 125.8±9.2 | 123.3±16.5 | 118.5±12.5 | 111.3±10.5 | 123.2±13.8 |
| PaCO2 , mmHg | 35.2±2.6 | 31.5±3.1* | 32.7±2.1 | 33.3±3.2 | 36.3±2.2 | 33.9±3.4 |
| Hb, g/dL | 16.0±1.5 | 11.1±0.5*** | 12.2±1.2*** | 12.9±1.6** | 13.1±1.6* | 13.2±1.6* |
| Hct, % | 45.3±1.6 | 34.2±1.6*** | 35.8±2.7*** | 38.1±1.8*** | 38.0±2.0** | 43.8±1.7 |
| Glu, mmol/L | 12.3±2.0 | 22.0±3.5*** | 24.3±3.4*** | 22.2±4.3*** | 16.7±2.3** | 14.3±2.3 |
| K+ , mmol/L | 4.5±0.2 | 5.4±0.4*** | 5.1±0.4** | 5.3±0.3*** | 5.2±0.4** | 5.2±0.6* |
Figure 5.
Changes in peripheral blood inflammatory cytokines in mice models with severe trauma and 30% blood loss measured using ELISA. A: IL-6 levels; B: TNF-α levels; C: MCP-1 levels; D: IL-1β; E: IL-4 levels; F: IL-10 levels. Data are presented as mean ± standard error of the mean (SEM) (n=6). Levene’s test was used to evaluate the homogeneity of variances before performing multiple group comparisons. When the assumption of homogeneity was met, one-way ANOVA followed by Dunnett’s post-hoc test was employed to compare differences between time points and the sham group. For groups with unequal variances, the Games-Howell test was applied. *P< 0.05. ELISA: enzyme-linked immunosorbent assay; IL: interleukin; TNF: tumor necrosis factor; MCP: monocyte chemoattractant protein.
| 1 |
Lord JM, Midwinter MJ, Chen YF, Belli A, Brohi K, Kovacs EJ, et al. The systemic immune response to trauma: an overview of pathophysiology and treatment. Lancet. 2014; 384(9952): 1455-65.
doi: 10.1016/S0140-6736(14)60687-5 pmid: 25390327 |
| 2 |
Jiang BG, Liang S, Peng ZR, Cong HZ, Levy M, Cheng Q, et al. Transport and public health in China: the road to a healthy future. Lancet. 2017; 390(10104): 1781-91.
doi: S0140-6736(17)31958-X pmid: 29047445 |
| 3 | Fecher A, Stimpson A, Ferrigno L, Pohlman TH. The pathophysiology and management of hemorrhagic shock in the polytrauma patient. J Clin Med. 2021; 10(20): 4793. |
| 4 | Thompson KB, Krispinsky LT, Stark RJ. Late immune consequences of combat trauma: a review of trauma-related immune dysfunction and potential therapies. Mil Med Res. 2019; 6(1): 11. |
| 5 | Picetti E, Rossi S, Abu-Zidan FM, Ansaloni L, Armonda R, Baiocchi GL, et al. WSES consensus conference guidelines: monitoring and management of severe adult traumatic brain injury patients with polytrauma in the first 24 hours. World J Emerg Surg. 2019; 14: 53. |
| 6 | Skelton JK, Purcell R. Preclinical models for studying immune responses to traumatic injury. Immunology. 2021; 162(4): 377-88. |
| 7 |
Gentile LF, Nacionales DC, Cuenca AG, Armbruster M, Ungaro RF, Abouhamze AS, et al. Identification and description of a novel murine model for polytrauma and shock. Crit Care Med. 2013; 41(4): 1075-85.
doi: 10.1097/CCM.0b013e318275d1f9 pmid: 23399937 |
| 8 | Suchy FP, Karigane D, Nakauchi Y, Higuchi M, Zhang JY, Pekrun K, et al. Genome engineering with Cas9 and AAV repair templates generates frequent concatemeric insertions of viral vectors. Nat Biotechnol. 2025; 43(2): 204-13. |
| 9 |
Pfeifer R, Lichte P, Schreiber H, Sellei RM, Dienstknecht T, Sadeghi C, et al. Models of hemorrhagic shock: differences in the physiological and inflammatory response. Cytokine. 2013; 61(2): 585-90.
doi: 10.1016/j.cyto.2012.10.022 pmid: 23178149 |
| 10 |
Wallen TE, Singer KE, Elson NC, Baucom MR, England LG, Schuster RM, et al. Defining endotheliopathy in murine polytrauma models. Shock. 2022; 57(6): 291-8.
doi: 10.1097/SHK.0000000000001940 pmid: 35759308 |
| 11 |
Yao ZH, Huang Y, Luo GX, Wu J, He WF. A biological membrane-based novel excisional wound-splinting model in mice (With video). Burns Trauma. 2014; 2(4): 196-200.
doi: 10.4103/2321-3868.143625 pmid: 27602382 |
| 12 |
Barry M, Trivedi A, Miyazawa BY, Vivona LR, Khakoo M, Zhang HQ, et al. Cryoprecipitate attenuates the endotheliopathy of trauma in mice subjected to hemorrhagic shock and trauma. J Trauma Acute Care Surg. 2021; 90(6): 1022-31.
doi: 10.1097/TA.0000000000003164 pmid: 33797484 |
| 13 | Kirk RGW. Recovering The principles of humane experimental technique: the 3Rs and the human essence of animal research. Sci Technol Human Values. 2018; 43(4): 622-48. |
| 14 | Li R, Ye JJ, Gan LB, Zhang MW, Sun DY, Li YZ, et al. Traumatic inflammatory response: pathophysiological role and clinical value of cytokines. Eur J Trauma Emerg Surg. 2024; 50(4): 1313-30. |
| 15 | Bonaroti J, Billiar I, Moheimani H, Wu JR, Namas R, Li S, et al. Plasma proteomics reveals early, broad release of chemokine, cytokine, TNF, and interferon mediators following trauma with delayed increases in a subset of chemokines and cytokines in patients that remain critically ill. Front Immunol. 2022; 13: 1038086. |
| 16 |
van Griensven M. Cytokines as biomarkers in polytraumatized patients. Unfallchirurg. 2014; 117(8): 699-702.
doi: 10.1007/s00113-013-2543-6 pmid: 25116012 |
| 17 | Hazeldine J, Naumann DN, Toman E, Davies D, Bishop JRB, Su ZJ, et al. Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: a prospective cohort study. PLoS Med. 2017; 14(7): e1002338. |
| 18 |
Wrba L, Palmer A, Braun CK, Huber-Lang M. Evaluation of gut-blood barrier dysfunction in various models of trauma, hemorrhagic shock, and burn injury. J Trauma Acute Care Surg. 2017; 83(5): 944-53.
doi: 10.1097/TA.0000000000001654 pmid: 28700414 |
| 19 | Chen XC, Li XJ, Lu HM, Xu YL, Wei Y, Cao K, et al. Mouse model of critical persistent inflammation, immunosuppression, and catabolism syndrome. Shock. 2022; 57(2): 238-45. |
| 20 | Calzia E, Huber-Lang M, Ignatius A, Radermacher P, Thiemermann AC. Modeling traumatic-hemorrhagic shock—nothing is simple and easy. Shock. 2012; 38(6): 685-6. |
| 21 |
Denk S, Weckbach S, Eisele P, Braun CK, Wiegner R, Ohmann JJ, et al. Role of hemorrhagic shock in experimental polytrauma. Shock. 2018; 49(2): 154-63.
doi: 10.1097/SHK.0000000000000925 pmid: 28614141 |
| 22 | Lomas-Niera JL, Perl M, Chung CS, Ayala A. Shock and hemorrhage: an overview of animal models. Shock. 2005; 24(Suppl 1): 33-9. |
| 23 | Redl H, Bahrami S. Large animal models: baboons for trauma, shock, and sepsis studies. Shock. 2005; 24(Suppl 1): 88-93. |
| 24 | Weber B, Lackner I, Haffner-Luntzer M, Palmer A, Pressmar J, Scharffetter-Kochanek K, et al. Modeling trauma in rats: similarities to humans and potential pitfalls to consider. J Transl Med. 2019; 17(1): 305. |
| 25 | Giacomotto J, Ségalat L. High-throughput screening and small animal models, where are we? Br J Pharmacol. 2010; 160(2): 204-16. |
| 26 |
Grada A, Mervis J, Falanga V. Research techniques made simple: animal models of wound healing. J Invest Dermatol. 2018; 138(10): 2095-105.e1.
doi: 10.1016/j.jid.2018.08.005 |
| 27 |
Breschi A, Gingeras TR, Guigó R. Comparative transcriptomics in human and mouse. Nat Rev Genet. 2017; 18(7): 425-40.
doi: 10.1038/nrg.2017.19 pmid: 28479595 |
| 28 | Consortium MGS, Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, et al. Initial sequencing and comparative analysis of the mouse genome. Nature. 2002; 420(6915): 520-62. |
| 29 |
Zhou J, Biesterveld BE, Li YQ, Wu ZY, Tian YZ, Williams AM, et al. Peptidylarginine deiminase 2 knockout improves survival in hemorrhagic shock. Shock. 2020; 54(4): 458-63.
doi: 10.1097/SHK.0000000000001489 pmid: 31764615 |
| 30 |
Stortz JA, Raymond SL, Mira JC, Moldawer LL, Mohr AM, Efron PA. Murine models of sepsis and trauma: can we bridge the gap? ILAR J. 2017; 58(1): 90-105.
doi: 10.1093/ilar/ilx007 pmid: 28444204 |
| 31 |
Feng YH, Huang YL, Wang Y, Wang P, Wang FJ. Severe burn injury alters intestinal microbiota composition and impairs intestinal barrier in mice. Burns Trauma. 2019; 7: 20.
doi: 10.1186/s41038-019-0156-1 pmid: 31312663 |
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