Full Text:   <2430>

Summary:  <1589>

CLC number: R605.971

On-line Access: 2017-05-04

Received: 2016-08-23

Revision Accepted: 2016-10-17

Crosschecked: 2017-04-10

Cited: 0

Clicked: 4079

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.5 P.402-409


Immune recovery after fluid resuscitation in rats with severe hemorrhagic shock

Author(s):  Feng Yao, Yuan-qiang Lu, Jiu-kun Jiang, Lin-hui Gu, Han-zhou Mou

Affiliation(s):  Department of Emergency Medicine, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; more

Corresponding email(s):   luyuanqiang201@hotmail.com, luyuanqiang@zju.edu.cn

Key Words:  Regulatory T cells, Helper T cells, Cytotoxic T cells, Hemorrhagic shock

Feng Yao, Yuan-qiang Lu, Jiu-kun Jiang, Lin-hui Gu, Han-zhou Mou. Immune recovery after fluid resuscitation in rats with severe hemorrhagic shock[J]. Journal of Zhejiang University Science B, 2017, 18(5): 402-409.

@article{title="Immune recovery after fluid resuscitation in rats with severe hemorrhagic shock",
author="Feng Yao, Yuan-qiang Lu, Jiu-kun Jiang, Lin-hui Gu, Han-zhou Mou",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Immune recovery after fluid resuscitation in rats with severe hemorrhagic shock
%A Feng Yao
%A Yuan-qiang Lu
%A Jiu-kun Jiang
%A Lin-hui Gu
%A Han-zhou Mou
%J Journal of Zhejiang University SCIENCE B
%V 18
%N 5
%P 402-409
%@ 1673-1581
%D 2017
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1600370

T1 - Immune recovery after fluid resuscitation in rats with severe hemorrhagic shock
A1 - Feng Yao
A1 - Yuan-qiang Lu
A1 - Jiu-kun Jiang
A1 - Lin-hui Gu
A1 - Han-zhou Mou
J0 - Journal of Zhejiang University Science B
VL - 18
IS - 5
SP - 402
EP - 409
%@ 1673-1581
Y1 - 2017
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1600370

Objective: To investigate the effects of resuscitation with normal saline (NS), hypertonic saline (HTS), and hydroxyethyl starch (HES) on regulatory T cells (Tregs), helper T 1 (Th1)/Th2 and cytotoxic T 1 (Tc1)/Tc2 profiles in the treatment of hemorrhagic shock. Methods: Rats subjected to severe hemorrhagic shock were resuscitated for 30 min with NS (n=8), HTS (n=8), or HES (n=8); sham (n=8) and naive control (n=8) groups were used for comparison. Following fluid resuscitation, the whole shed blood was reinfused for 30 min, and the rats were observed with continuous hemodynamic monitoring for 120 min. CD4+CD25+Foxp3+ Treg proportions, Th1/Th2 and Tc1/Tc2 profiles in spleen were analyzed by three-color flow cytometry. Results: The proportion of CD4+CD25+Foxp3+ Tregs and ratios of Th1/Th2 and Tc1/Tc2 did not differ among control, sham, and HTS groups, but were significantly lower in NS and HES groups (both P<0.05 vs. sham); NS and HES levels were similar. The level of Tc1 was significantly increased in HTS (P<0.05 vs. sham), and levels of Tc2 were increased in NS, HES, and HTS groups compared to sham (all P<0.05), but did not differ from each other. Conclusions: HTS resuscitation has a greater impact on immune system recovery than NS or HES by preserving the proportion of Tregs and maintaining the balance between Th1/Th2 and Tc1/Tc2 cells in the spleen. Thus, HTS resuscitation provides potential immunomodulatory activity in the early stage after hemorrhagic shock.


方法:将SD雄性大鼠随机分成5组,其中对照组和Sham组(假手术)仅作为比较,其余三组在建立严重失血性休克大鼠模型后,采用不同的液体复苏:等渗盐水(NS组)、高渗盐水(HTS组)和羟乙基淀粉(HES组)。然后再灌注30分钟,并持续监测血液动力学120分钟,最后心脏穿刺,取脾脏组织,通过三色荧光标记流式细胞术进一步分析CD4+CD25+Foxp3+ Treg细胞含量,以及Th1/Th2和Tc1/Tc2的比值。
结论:液体复苏后大鼠脾脏中CD4+CD25+Foxp3+ Tregs细胞含量、Th1/Th2和Tc1/Tc2的比值在对照组、Sham组和HTS组中无差异,并都显著高于NS组和HES组。与Sham组比较,HTS组中Tc1水平明显升高,而NS组、HES组和HTS组中Tc2水平均有升高,且三组之间Tc2水平无差别。因此,对于维持脾脏中Treg细胞含量、Th1/Th2和Tc1/Tc2平衡的作用上,HTS液体复苏对免疫系统的影响大于NS和HES。综上所述,在失血性休克后的早期阶段HTS复苏可提供潜在的免疫修复作用。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Alam, H.B., Stanton, K., Koustova, E., et al., 2004. Effect of different resuscitation strategies on neutrophil activation in a swine model of hemorrhagic shock. Resuscitation, 60(1):91-99.

[2]Angele, M.K., Schneider, C.P., Chaudry, I.H., 2008. Bench-to-bedside review: latest results in hemorrhagic shock. Crit. Care, 12(4):218.

[3]Barros, J.M., do Nascimento, P.Jr., Marinello, J.L., et al., 2011. The effects of 6% hydroxyethyl starch-hypertonic saline in resuscitation of dogs with hemorrhagic shock. Anesth. Analg., 112(2):395-404.

[4]Belkaid, Y., Rouse, B.T., 2005. Natural regulatory T cells in infectious disease. Nat. Immunol., 6(4):353-360.

[5]Brøchner, A.C., Toft, P., 2009. Pathophysiology of the systemic inflammatory response after major accidental trauma. Scand. J. Trauma Resusc. Emerg. Med., 17:43.

[6]Burgents, J.E., Moran, T.P., West, M.L., et al., 2010. The immunosuppressive tumor environment is the major impediment to successful therapeutic vaccination in Neu transgenic mice. J. Immunother., 33(5):482-491.

[7]Carambia, A., Freund, B., Schwinge, D., et al., 2014. TGF-β-dependent induction of CD4+CD25+Foxp3+ Tregs by liver sinusoidal endothelial cells. J. Hepatol., 61(3):594-599.

[8]Chen, J.M., Lv, J., Ma, K., et al., 2014. Assessment of internal mammary artery injury after blunt chest trauma: a literature review. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 15(10):864-869.

[9]Cui, Y., Sun, B., Wang, C., et al., 2014. Effects of different types of hydroxyethyl starch (HES) on microcirculation perfusion and tissue oxygenation in patients undergoing liver surgery. Int. J. Clin. Exp. Med., 7(3):631-639.

[10]Fernandes, C.I., Llimona, F., Godoy, L.C., et al., 2009. Treatment of hemorrhagic shock with hypertonic saline solution modulates the inflammatory response to live bacteria in lungs. Braz. J. Med. Biol. Res., 42(10): 892-901.

[11]Fogle, J.E., Mexas, A.M., Tompkins, W.A., et al., 2010a. CD4+CD25+ T regulatory cells inhibit CD8+ IFN-γ production during acute and chronic FIV infection utilizing a membrane TGF-β-dependent mechanism. AIDS Res. Hum. Retroviruses, 26(2):201-216.

[12]Fogle, J.E., Tompkins, W.A., Tompkins, M.B., 2010b. CD4+CD25+ T regulatory cells from FIV+ cats induce a unique anergic profile in CD8+ lymphocyte targets. Retrovirology, 7:97.

[13]Gao, J., Zhao, W.X., Xue, F.S., et al., 2009. Effects of different resuscitation fluids on acute lung injury in a rat model of uncontrolled hemorrhagic shock and infection. J. Trauma, 67(6):1213-1219.

[14]Gurfinkel, V., Poggetti, R.S., Fontes, B., et al., 2003. Hypertonic saline improves tissue oxygenation and reduces systemic and pulmonary inflammatory response caused by hemorrhagic shock. J. Trauma, 54(6):1137-1145.

[15]Isayama, K., Murao, Y., Saito, F., et al., 2012. Effects of hypertonic saline on CD4+CD25+Foxp3+ regulatory T cells after hemorrhagic shock in relation to iNOS and cytokines. J. Surg. Res., 172(1):137-145.

[16]Ledderose, C., Bao, Y., Kondo, Y., et al., 2016. Purinergic signaling and the immune response in sepsis: a review. Clin. Ther., 38(5):1054-1065.

[17]Li, J., Qian, C.N., Zeng, Y.X., 2009. Regulatory T cells and EBV associated malignancies. Int. Immunopharmacol., 9(5):590-592.

[18]Loomis, W.H., Namiki, S., Ostrom, R.S., et al., 2003. Hypertonic stress increases T cell interleukin-2 expression through a mechanism that involves ATP release, P2 receptor, and p38 MAPK activation. J. Biol. Chem., 278(7):4590-4596.

[19]Lu, Y.Q., Cai, X.J., Gu, L.H., et al., 2007. Hypertonic saline resuscitation maintains a more balanced profile of T-lymphocyte subpopulations in a rat model of hemorrhagic shock. J. Zhejiang Univ.-Sci. B, 8(1):70-75.

[20]Lu, Y.Q., Huang, W.D., Cai, X.J., et al., 2008. Hypertonic saline resuscitation reduces apoptosis of intestinal mucosa in a rat model of hemorrhagic shock. J. Zhejiang Univ.-Sci. B, 9(11):879-884.

[21]Lu, Y.Q., Gu, L.H., Huang, W.D., et al., 2010. Effect of hypertonic saline resuscitation on heme oxygenase-1 mRNA expression and apoptosis of the intestinal mucosa in a rat model of hemorrhagic shock. Chin. Med. J. (Engl.), 123(11):1453-1458.

[22]Lu, Y.Q., Gu, L.H., Zhang, Q., et al., 2013. Hypertonic saline resuscitation contributes to early accumulation of circulating myeloid-derived suppressor cells in a rat model of hemorrhagic shock. Chin. Med. J. (Engl.), 126(7):1317-1322.

[23]Maier, R.V., Alam, H.B., 2011. Hemostatic and pharmacologic resuscitation: results of a long-term survival study in a swine polytrauma model. J. Trauma, 70(3):636-645.

[24]Marcu, A.C., Paccione, K.E., Barbee, R.W., et al., 2007. Androstenetriol immunomodulation improves survival in a severe trauma hemorrhage shock model. J. Trauma, 63(3):662-669.

[25]Menger, M.D., Vollmar, B., 2004. Surgical trauma: hyperinflammation versus immunosuppression? Langenbecks Arch. Surg., 389(6):475-484.

[26]Miller, A.C., Rashid, R.M., Elamin, E.M., 2007. The “T” in trauma: the helper T-cell response and the role of immunomodulation in trauma and burn patients. J. Trauma, 63(6):1407-1417.

[27]Moore, F.A., McKinley, B.A., Moore, E.E., 2004. The next generation in shock resuscitation. Lancet, 363(9425): 1988-1996.

[28]Moore, F.A., McKinley, B.A., Moore, E.E., et al., 2006. Inflammation and the host response to injury, a large-scale collaborative project: patient-oriented research core— standard operating procedures for clinical care. III. Guidelines for shock resuscitation. J. Trauma, 61(1):82-89.

[29]Murao, Y., Loomis, W., Wolf, P., et al., 2003a. Effect of dose of hypertonic saline on its potential to prevent lung tissue damage in a mouse model of hemorrhagic shock. Shock, 20(1):29-34.

[30]Murao, Y., Hata, M., Ohnishi, K., et al., 2003b. Hypertonic saline resuscitation reduces apoptosis and tissue damage of the small intestine in a mouse model of hemorrhagic shock. Shock, 20(1):23-28.

[31]Murao, Y., Isayama, K., Saito, F., et al., 2009. Effect of hypertonic saline resuscitation on CD4+CD25+ regulatory T cells and γδ T cells after hemorrhagic shock and resuscitation in relation to apoptosis and iNOS. J. Trauma, 67(5):975-982.

[32]National Research Council, 2011. Guide for the Care and Use of Laboratory Animals, 8th Ed. The National Academies Press, Washington, DC, USA. http://grants.nih.gov/grants/olaw/Guide-for-the-Care-and-Use-of-Laboratory-Animals.pdf [Accessed on Apr. 10, 2016].

[33]Tang, L., Bai, J., Chung, C.S., et al., 2014. Active players in resolution of shock/sepsis induced indirect lung injury: immunomodulatory effects of Tregs and PD-1. J. Leukoc. Biol., 96(5):809-820.

[34]Vallet, B., 2011. Intravascular volume expansion: which surrogate markers could help the clinician to assess improved tissue perfusion? Anesth. Analg., 112(2):258-259.

[35]Vincenzi, R., Cepeda, L.A., Pirani, W.M., et al., 2009. Small volume resuscitation with 3% hypertonic saline solution decrease inflammatory response and attenuates end organ damage after controlled hemorrhagic shock. Am. J. Surg., 198(3):407-414.

[36]Woehrle, T., Yip, L., Manohar, M., et al., 2010. Hypertonic stress regulates T cell function via pannexin-1 hemichannels and P2X receptors. J. Leukoc. Biol., 88(6):1181-1189.

[37]Yip, L., Cheung, C.W., Corriden, R., et al., 2007. Hypertonic stress regulates T-cell function by the opposing actions of extracellular adenosine triphosphate and adenosine. Shock, 27(3):242-250.

[38]Zhang, A.B., Qian, Y.G., Zheng, S.S., 2016. Prognostic significance of regulatory T lymphocytes in patients with hepatocellular carcinoma. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 17(12):984-991.

[39]Zhang, Y., Liang, L., Wu, W., et al., 2008. Resuscitation with hydroxyethyl starch solution prevents CD4+ T-lymphocyte apoptosis and modulates the balance of T helper type 1 and T helper type 2 responses in the rat with traumatic virgule/shill hemorrhagic shock. Shock, 30(6):692-698.

[40]Zhao, X.H., Jiang, J.K., Lu, Y.Q., 2015. Evaluation of efficacy of resin hemoperfusion in patients with acute 2,4-dinitrophenol poisoning by dynamic monitoring of plasma toxin concentration. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 16(8):720-726.

[41]Zhao, X.J., Pen, Z., Li, P., et al., 2013. β-receptor blocker influences return of spontaneous circulation and chemical examination in rats during cardiopulmonary resuscitation. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 14(6): 505-510.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE