Effects of Shen-fu injection on lung injury in a porcine model of hemorrhagic shock

Qiang Zhang , Zhao Liu , Gu Wei , Bo Liu

Emergency and Critical Care Medicine ›› 2026, Vol. 6 ›› Issue (3) : 149

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Emergency and Critical Care Medicine ›› 2026, Vol. 6 ›› Issue (3) :149 DOI: 10.1097/EC9.0000000000000194
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Effects of Shen-fu injection on lung injury in a porcine model of hemorrhagic shock
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Abstract

Background: Since it remains unclear whether Shen-fu injection (SFI) could be used in hemorrhagic shock (HS), this study aimed to explore the effects of SFI on lung injury caused by HS in a porcine model.
Methods: After HS induction, 32 pigs were allocated using simple randomization to four groups (n = 8 each): Group I (no resuscitation), Group II (shed blood reinfusion), Group III (reinfusion + saline 3 mL/kg), and Group IV (reinfusion + Shenfu injection 3 mL/kg). At 6 hours after HS, lung tissue was collected to measure IL‑6, IL‑8, IL‑4, and IL‑10 by ELISA, and to evaluate apoptosis by immunohistochemistry and transmission electron microscopy. Tissues from non‑survivors were obtained at the time of death and analyzed when available.
Results: Of the 32 randomized animals, 23 survived to 6 hours (Group I, 4/8; Group II, 6/8; Group III, 6/8; Group IV, 7/8). Cytokine analysis revealed that group IV exhibited significantly reduced levels of proinflammatory cytokines, including IL-6 and IL-8, concomitant with elevated concentrations of anti-inflammatory cytokines, specifically IL-4 and IL-10 (P < 0.05). Additionally, group IV demonstrated significantly elevated superoxide dismutase enzymatic activity, alongside enhanced Na+-K+-ATPase and Ca2+-ATPase activities, coupled with markedly reduced malondialdehyde levels (P < 0.05). Immunohistochemical analysis revealed downregulated caspase-3 expression and upregulated Bcl-2 expression in group IV, collectively indicating attenuated apoptotic activity. Ultrastructural examination of pulmonary tissues further demonstrated that SFI administration effectively ameliorated alveolar edema, hemorrhage, and inflammatory cell infiltration, while concurrently mitigating epithelial cell apoptosis and mitochondrial injury relative to the other experimental groups.
Conclusion: Among animals surviving to the 6‑hour assessment, SFI was associated with differences in selected inflammatory, oxidative‑stress, apoptosis, and histological markers. Because of differential mortality, small outcome‑specific sample sizes, and limited quantitative histology, these findings should be considered exploratory and do not establish improved survival or hemodynamic benefit.

Keywords

Hemorrhagic shock / Lung / Shen-fu

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Qiang Zhang, Zhao Liu, Gu Wei, Bo Liu. Effects of Shen-fu injection on lung injury in a porcine model of hemorrhagic shock. Emergency and Critical Care Medicine, 2026, 6 (3) : 149 DOI:10.1097/EC9.0000000000000194

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References

[1]

Kuo K, Palmer L. Pathophysiology of hemorrhagic shock. J Vet Emerg Crit Care (San Antonio). 2022; 32(S1): 22-31. doi: 10.1111/vec.13126

[2]

Callén AG, Torres MP, Castaño DV, et al. Trauma team activation criteria for potential major trauma in the adult population: a narrative review. Emerg Crit Care Med. 2024; 4(4): 163-173. doi: 10.1097/EC9.0000000000000136

[3]

Meza MK, Rosa C, Sublette C, et al. Navigating hemorrhagic shock: biomarkers, therapies, and challenges in clinical care. Biomedicines 2024; 12(12): 2864. doi: 10.3390/biomedicines12122864

[4]

Markl-Le Levé A, Haller I, Bachler M. Fluid management in hemorrhagic shock. Curr Opin Anaesthesiol. 2025; 38(3): 316-322. doi: 10.1097/ACO.0000000000001481

[5]

Gomez MK, Neff LP. Optimizing pediatric resuscitation: evidence-based approaches and emerging trends. Am Surg. 2025; 91(5): 901-910. doi: 10.1177/00031348251329503

[6]

Davis JA, Manoach S, Heerdt P, Berlin DA. Management of respiratory failure in hemorrhagic shock. Ann Am Thorac Soc. 2024; 21(7): 993-997. doi: 10.1513/AnnalsATS.202310-905CME

[7]

Elansary NN, Stonko DP, Treffalls RN, Abdou H, Madurska MJ, Morrison JJ. Class of hemorrhagic shock is associated with progressive diastolic coronary flow reversal and diminished left ventricular function. Front Physiol. 2022; 13: 1033784. doi: 10.3389/fphys.2022.1033784

[8]

Morris MC, Kim Y, Blakeman TC, et al. Early identification of acute lung injury in a porcine model of hemorrhagic shock. J Surg Res. 2020; 247: 453-460. doi: 10.1016/j.jss.2019.09.060

[9]

Papapanagiotou P, Xanthos T, Gulati A, et al. Centhaquin improves survival in a swine model of hemorrhagic shock. J Surg Res. 2016; 200(1): 227-235. doi: 10.1016/j.jss.2015.06.056

[10]

Zhang MQ, Li CS. Therapeutic effects of shenfu injection in shock. Chin J Integr Med. 2023; 29(12): 1142-1146. doi: 10.1007/s11655-023-3631-2

[11]

Yang H, Liu L, Gao W, Liu K, Qi LW, Li P. Direct and comprehensive analysis of ginsenosides and diterpene alkaloids in Shenfu injection by combinatory liquid chromatography-mass spectrometric techniques. J Pharm Biomed Anal. 2014; 92: 13-21. doi: 10.1016/j.jpba.2013.12.041

[12]

Tan G, Zhou Q, Liu K, et al. Cross-platform metabolic profiling deciphering the potential targets of Shenfu injection against acute viral myocarditis in mice. J Pharm Biomed Anal. 2018; 160: 1-11. doi: 10.1016/j.jpba.2018.07.042

[13]

Liao J, Qin C, Wang Z, et al. Effect of shenfu injection in patients with septic shock: a systematic review and meta-analysis for randomized clinical trials. J Ethnopharmacol. 2024; 320: 117431. doi: 10.1016/j.jep.2023.117431

[14]

Zhang MY, Ji XF, Wang S, Li C-S. Shen-fu injection attenuates postresuscitation lung injury in a porcine model of cardiac arrest. Resuscitation. 2012; 83(9): 1152-1158. doi: 10.1016/j.resuscitation.2012.01.041

[15]

Roesner JP, Petzelbauer P, Koch A, et al. Bbeta15-42 (FX06) reduces pulmonary, myocardial, liver, and small intestine damage in a pig model of hemorrhagic shock and reperfusion. Crit Care Med. 2009; 37(2): 598-605. doi: 10.1097/CCM.0b013e3181959a12

[16]

Wu J, Li Z, Yuan W, et al. Shenfu injection improves cerebral microcirculation and reduces brain injury in a porcine model of hemorrhagic shock. Clin Hemorheol Microcirc 2021; 78(2): 175-185. doi: 10.3233/CH-211100

[17]

Velez DR. The history of hemorrhagic shock and damage control resuscitation. Am Surg. 2022; 88(11): 2656-2659. doi: 10.1177/00031348211011098

[18]

Cannon JW. Hemorrhagic shock. N Engl J Med. 2018; 378(4): 370-379. doi: 10.1056/NEJMra1705649

[19]

Li M, Li G, Yu B, Luo Y, Li Q. Activation of hypoxia-inducible factor-1α via succinate dehydrogenase pathway during acute lung injury induced by trauma/hemorrhagic shock. Shock. 2020; 53(2): 208-216. doi: 10.1097/SHK.0000000000001347

[20]

Shao F, Li H, Li D, Li C. Effects of Shenfu injection on survival and neurological outcome after out-of-hospital cardiac arrest: a randomised controlled trial. Resuscitation. 2020; 150: 139-144. doi: 10.1016/j.resuscitation.2019.11.010

[21]

Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003; 348(2): 138-150. doi: 10.1056/NEJMra021333

[22]

Zhang Q, Li CS, Wang S, Gu W. Effects of Chinese medicine shen-fu injection on the expression of inflammatory cytokines and complements during post-resuscitation immune dysfunction in a porcine model. Chin J Integr Med. 2016; 22(2): 101-109. doi: 10.1007/s11655-014-1857-8

[23]

Huang P, Guo Y, Hu X, Fang X, Xu X, Liu Q. Mechanism of Shenfu injection in suppressing inflammation and preventing sepsis-induced apoptosis in murine cardiomyocytes based on network pharmacology and experimental validation. J Ethnopharmacol. 2024; 322: 117599. doi: 10.1016/j.jep.2023.117431

[24]

Razi A, Ayoub IM, Baetiong A, et al. Oral-mucosal PCO2 during hemorrhagic shock closely monitors its time course, severity, and reversal outperforming blood lactate measurement. Resusc Plus. 2024; 20: 100814. doi: 10.1016/j.resplu.2024.100814

[25]

Fuller BM, Dellinger RP. Lactate as a hemodynamic marker in the critically ill. Curr Opin Crit Care. 2012; 18(3): 267-272. doi: 10.1097/MCC.0b013e3283532b8a

[26]

Huang P, Guo Y, Zhao G, Li B, Liu Q. Efficacy and safety of Shenfu injection for septic shock: a systematic review and meta-analysis of randomized controlled trials. Am J Emerg Med. 2019; 37(12): 2197-2204. doi: 10.1016/j.ajem.2019.03.032

[27]

Faria I, Thivalapill N, Makin J, Puyana JC, Raykar N. Bleeding, hemorrhagic shock, and the global blood supply. Crit Care Clin. 2022; 38(4): 775-793. doi: 10.1016/j.ccc.2022.06.013

[28]

Zhu Y, Ma S, Deng HY, et al. The characteristics of organ function damage of hemorrhagic shock in hot environment and the effect of hypothermic fluid resuscitation. Shock. 2022; 57(4): 526-535. doi: 10.1097/SHK.0000000000001873

[29]

Wang Y, Liu Y, Zhang XY, et al. Ginsenoside Rg1 regulates innate immune responses in macrophages through differentially modulating the NF-κB and PI3K/Akt/mTOR pathways. Int Immunopharmacol. 2014; 23(1): 77-84. doi: 10.1016/j.jep.2023.117599

[30]

Huang P, Yu X, Gao Z, et al. Shenfu injection ameliorates hepatic ischemia-reperfusion injury through induction of ferroptosis via JAK2/STAT3 pathway. J Ethnopharmacol. 2025; 348: 119889. doi: 10.1016/j.jep.2025.119889

[31]

Wang YL, Wang CY, Zhang BJ, Zhang Z-Z. Shenfu injection suppresses apoptosis by regulation of Bcl-2 and caspase-3 during hypoxia/reoxygenation in neonatal rat cardiomyocytes in vitro. Mol Biol Rep. 2009; 36(2): 365-370. doi: 10.1007/s11033-007-9188-x

[32]

Gu W, Li C, Yin W, Guo Z, Hou X, Zhang D. Shen-fu injection reduces postresuscitation myocardial dysfunction in a porcine model of cardiac arrest by modulating apoptosis. Shock. 2012; 38(3): 301-306. doi: 10.1097/SHK.0b013e31825f6632

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