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Journal of Zhejiang University SCIENCE B 2008 Vol.9 No.11 P.871~878


Albumin resuscitation protects against traumatic/hemorrhagic shock-induced lung apoptosis in rats

Author(s):  Yun ZHANG, Zhong-yan LIANG, Shao-yang ZHANG, Fang-fang HUANG, Wei WU, Yuan GAO, Zuo-bing CHEN

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

Corresponding email(s):   chenzuobing@hotmail.com

Key Words:  Traumatic/hemorrhagic shock (T/HS), Mitogen-activated protein kinase (MAPK), Nuclear factor &kappa, B (NF-&kappa, B), Albumin, Apoptosis

Yun ZHANG, Zhong-yan LIANG, Shao-yang ZHANG, Fang-fang HUANG, Wei WU, Yuan GAO, Zuo-bing CHEN. Albumin resuscitation protects against traumatic/hemorrhagic shock-induced lung apoptosis in rats[J]. Journal of Zhejiang University Science B, 2008, 9(11): 871~878.

@article{title="Albumin resuscitation protects against traumatic/hemorrhagic shock-induced lung apoptosis in rats",
author="Yun ZHANG, Zhong-yan LIANG, Shao-yang ZHANG, Fang-fang HUANG, Wei WU, Yuan GAO, Zuo-bing CHEN",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Albumin resuscitation protects against traumatic/hemorrhagic shock-induced lung apoptosis in rats
%A Zhong-yan LIANG
%A Shao-yang ZHANG
%A Fang-fang HUANG
%A Wei WU
%A Yuan GAO
%A Zuo-bing CHEN
%J Journal of Zhejiang University SCIENCE B
%V 9
%N 11
%P 871~878
%@ 1673-1581
%D 2008
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0820130

T1 - Albumin resuscitation protects against traumatic/hemorrhagic shock-induced lung apoptosis in rats
A1 - Yun ZHANG
A1 - Zhong-yan LIANG
A1 - Shao-yang ZHANG
A1 - Fang-fang HUANG
A1 - Wei WU
A1 - Yuan GAO
A1 - Zuo-bing CHEN
J0 - Journal of Zhejiang University Science B
VL - 9
IS - 11
SP - 871
EP - 878
%@ 1673-1581
Y1 - 2008
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0820130

Objective: To determine the effects of albumin administration on lung injury and apoptosis in traumatic/hemorrhagic shock (T/HS) rats. Methods: Studies were performed on an in vivo model of spontaneously breathing rats with induced T/HS; the rats were subjected to femur fracture, ischemia for 30 min, and reperfusion for 20 min with Ringer’s lactate solution (RS) or 5% (w/v) albumin (ALb), and the left lower lobes of the lungs were resected. Results: albumin administered during reperfusion markedly attenuated injury of the lung and decreased the concentration of lactic acid and the number of in situ TdT-mediated dUTP nick-end labelling (TUNEL)-positive cells. Moreover, immunohistochemistry performed 24 h after reperfusion revealed increases in the level of nuclear factor &kappa;b (NF-&kappa;b), and phosphorylated p38 mitogen-activated protein kinase (MAPK) in the albumin-untreated group was down-regulated by albumin treatment when compared with the sham rats. Conclusion: Resuscitation with albumin attenuates tissue injury and inhibits T/HS-induced apoptosis in the lung via the p38 MAPK signal transduction pathway that functions to stimulate the activation of NF-κB.

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


[1] Ayala, A., Chung, C.S., Song, G.Y., Chaudry, I.H., 2001. IL-10 mediation of activation-induced TH1 cell apoptosis and lymphoid dysfunction in polymicrobial sepsis. Cytokine, 14(1):37-48.

[2] Boura, C., Caron, A., Longrois, D., Mertes, P.M., Labrude, P., Menu, P., 2003. Volume expansion with modified hemoglobin solution, colloids, or crystalloid after hemorrhagic shock in rabbits: effects in skeletal muscle oxygen pressure and use versus arterial blood velocity and resistance. Shock, 19(2):176-182.

[3] Buckley, S., Barsky, L., Driscoll, B., Weinberg, K., Anderson, K.D., Warburton, D., 1998. Apoptosis and DNA damage in type 2 alveolar epithelial cells cultured from hyperoxic rats. Am. J. Physiol., 274(5 Pt 1):714-720.

[4] Cochrane Injuries Group Albumin Reviewers, 1998. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. Cochrane Injuries Group Albumin Reviewers. BMJ, 317(7153):235-240.

[5] Compton, C.N., Franko, A.P., Murray, M.T., Diebel, L.N., Dulchavsky, S.A., 1998. Signaling of apoptotic lung injury by lipid hydroperoxides. J. Trauma, 44(5):783-788.

[6] de Nigris, F., Lerman, A., Ignarro, L.J., Williams-Ignarro, S., Sica, V., Baker, A.H., Lerman, L.O., Geng, Y.J., Napoli, C., 2003. Oxidation-sensitive mechanisms, vascular apoptosis and atherosclerosis. Trends Mol. Med., 9(8):351-359.

[7] Deb, S., Martin, B., Sun, L., Ruff, P., Burris, D., Rich, N., DeBreux, S., Austin, B., Rhee, P., 1999. Resuscitation with lactated Ringer’s solution in rats with hemorrhagic shock induces immediate apoptosis. J. Trauma, 46(4):582-588.

[8] Deb, S., Sun, L., Martin, B., Talens, E., Burris, D., Kaufmann, C., Rich, N., Rhee, P., 2000. Lactated Ringer’s solution and hetastarch but not plasma resuscitation after rat hemorrhagic shock is associated with immediate lung apoptosis by the up-regulation of the Bax protein. J. Trauma, 49(1):47-53.

[9] Dubois, M.J., Orellana-Jimenez, C., Melot, C., De Backer, D., Berre, J., Leeman, M., Brimioulle, S., Appoloni, O., Creteur, J., Vincent, J.L., 2006. Albumin administration improves organ function in critically ill hypoalbuminemic patients: a prospective, randomized, controlled, pilot study. Crit. Care Med., 34(10):2536-2540.

[10] Emerson, T.E.Jr., 1989. Unique features of albumin: a brief review. Crit. Care Med., 17(7):690-694.

[11] Engel, J.M., Welters, I., Rupp, M., Langefeld, T., Ruwoldt, R., Menges, T., Hempelmann, G., 2001. Influence of colloid fluids on polymorphonuclear granulocyte function in vivo. Acta Anaesthesiol. Scand., 45(3):385-389.

[12] Esposito, C., Gerlach, H., Brett, J., Stern, D., Vlassara, H., 1989. Endothelial receptor-mediated binding of glucose-modified albumin is associated with increased monolayer permeability and modulation of cell surface coagulant properties. J. Exp. Med., 170(4):1387-1407.

[13] Genescà, M., Sola, A., Miquel, R., Pi, F., Xaus, C., Alfaro, V., Hotter, G., 2002. Role of changes in tissular nucleotides on the development of apoptosis during ischemia/ reperfusion in rat small bowel. Am. J. Pathol., 161(5):1839-1847.

[14] Hoefen, R.J., Berk, B.C., 2002. The role of MAP kinases in endothelial activation. Vascul. Pharmacol., 38(5):271-273.

[15] Horstick, G., Lauterbach, M., Kempf, T., Bhakdi, S., Heimann, A., Horstick, M., Meyer, J., Kempski, O., 2002. Early albumin infusion improves global and local hemodynamics and reduces inflammatory response in hemorrhagic shock. Crit. Care Med., 30(4):851-855.

[16] Ikeda, H., Suzuki, Y., Suzuki, M., Koike, M., Tamura, J., Tong, J., Nomura, M., Itoh, G., 1998. Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/ reperfusion injury to the rat intestinal epithelium. Gut, 42(4):530-537.

[17] Jiang, D.J., Jia, S.J., Dai, Z., Li, Y.J., 2006. Asymmetric dimethylarginine induces apoptosis via p38 MAPK/ caspase-3-dependent signaling pathway in endothelial cells. J. Mol. Cell. Cardiol., 40(4):529-539.

[18] Kentner, R., Safar, P., Behringer, W., Wu, X., Kagan, V.E., Tyurina, Y.Y., Henchir, J., Ma, L., Hsia, C.J., Tisherman, S.A., 2002. Early antioxidant therapy with Tempol during hemorrhagic shock increases survival in rats. J. Trauma, 53(5):968-977.

[19] Khan, T.A., Bianchi, C., Araujo, E.G., Ruel, M., Voisine, P., Sellke, F.W., 2003. Activation of pulmonary mitogen-activated protein kinases during cardiopulmonary bypass. J. Surg. Res., 115(1):56-62.

[20] Khan, T.A., Bianchi, C., Ruel, M., Voisine, P., Sellke, F.W., 2004. Mitogen-activated protein kinase pathways and cardiac surgery. J. Thorac. Cardiovasc. Surg., 127(3):806-811.

[21] Kim, H.J., Lee, H.S., Chong, Y.H., Kang, J.L., 2006. p38 mitogen-activated protein kinase up-regulates LPS-induced NF-kappaB activation in the development of lung injury and RAW 264.7 macrophages. Toxicology, 225(1):36-47.

[22] Lai, E.W., Toledo-Pereyra, L.H., Walsh, J., Lopez-Neblina, F., Anaya-Prado, R., 2004. The role of MAP kinases in trauma and ischemia-reperfusion. J. Invest. Surg., 17(1):45-53.

[23] Lu, Y.Q., Cai, X.J., Gu, L.H., Fan, Y.J., Wang, Q., Bao, D.G., 2005. Effects of three fluid resuscitation methods on apoptosis of visceral organs in rats with hemorrhagic shock. J. Zhejiang Univ. Sci. B, 6(9):907-912.

[24] Magnotti, L.J., Upperman, J.S., Xu, D.Z., Lu, Q., Deitch, E.A., 1998. Gut-derived mesenteric lymph but not portal blood increases endothelial cell permeability and promotes lung injury after hemorrhagic shock. Ann. Surg., 228(4):518-527.

[25] Matot, I., Zeira, E., Weiniger, C.F., Galun, E., Joshi, B.V., Jacobson, K.A., 2006. A3 adenosine receptors and mitogen-activated protein kinases in lung injury following in vivo reperfusion. Crit. Care, 10(2):R65.

[26] Nuytinck, H.K., Offermans, X.J., Kubat, K., Goris, J.A., 1988. Whole-body inflammation in trauma patients. An autopsy study. Arch. Surg., 123(12):1519-1524.

[27] Osband, A.J., Deitch, E.A., Hauser, C.J., Lu, Q., Zaets, S., Berezina, T., Machiedo, G.W., Rajwani, K.K., Xu, D.Z., 2004a. Albumin protects against gut-induced lung injury in vitro and in vivo. Ann. Surg., 24(2):331-339.

[28] Osband, A.J., Sifri, Z.C., Wang, L., Cohen, D., Hauser, C.J., Mohr, A.M., Deitch, E.A., Livingston, D.H., 2004b. Small volume albumin administration protects against hemorrhagic shock-induced bone marrow dysfunction. J. Trauma, 56(2):279-283.

[29] Peitzman, A.B., Billiar, T.R., Harbrecht, B.G., Kelly, E., Udekwu, A.O., Simmons, R.L., 1995. Hemorrhagic shock. Curr. Probl. Surg., 32(11):925-1002.

[30] Su, F., Cai, Y., Wang, Z., Rogiers, P., Vincent, J.L., 2007. Fluid resuscitation in severe sepsis and septic shock: albumin, hydroxyethyl starch, gelatin or Ringer’s lactate: does it really make a difference? Shock, 27(5):520-526.

[31] Sun, L.L., Ruff, P., Austin, B., Deb, S., Martin, B., Burris, D., Rhee, P., 1999. Early up-regulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in rats with hemorrhagic shock and resuscitation. Shock, 11(6):416-422.

[32] Toledo-Pereyra, L.H., Toledo, A.H., Walsh, J., Lopez-Neblina, F., 2004. Molecular signaling pathways in ischemia/ reperfusion. Exp. Clin. Transplant, 2(1):174-177.

[33] Vincent, J.L., Navickis, R.J., Wilkes, M.M., 2004. Morbidity in hospitalized patients receiving human albumin: a meta-analysis of randomized, controlled trials. Crit. Care Med., 32(10):2029-2038.

[34] Wang, H., Wang, Z., Chen, J., Wu, J., 2007. Apoptosis induced by NO via phosphorylation of p38 MAPK that stimulates NF-kappaB, p53 and caspase-3 activation in rabbit articular chondrocytes. Cell Biol. Int., 31(9):1027-1035.

[35] Wang, X., Zhou, Y., Kim, H.P., Song, R., Zarnegar, R., Ryter, S.W., Choi, A.M., 2004. Hepatocyte growth factor protects against hypoxia/reoxygenation-induced apoptosis in endothelial cells. J. Biol. Chem., 279(7):5237-5243.

[36] Waxman, K., 1996. Shock: ischemia, reperfusion, and inflammation. New Horiz., 4(2):153-160.

[37] Zhang, H., Voglis, S., Kim, C.H., Slutsky, A.S., 2003. Effects of albumin and Ringer’s lactate on production of lung cytokines and hydrogen peroxide after resuscitated hemorrhage and endotoxemia in rats. Crit. Care Med., 31(5):1515-1522.

[38] Zhou, Y.Q., He, C., Chen, Y.Q., Wang, D., Wang, M.H., 2003. Altered expression of the RON receptor tyrosine kinase in primary human colorectal adenocarcinomas: generation of different splicing variants and their oncogenic potential. Oncogene, 22(2):186-197.

[39] Zoellner, H., Höfler, M., Beckmann, R., Hufnagl, P., Vanyek, E., Bielek, E., Wojta, J., Fabry, A., Lockie, S., Binder, B.R., 1996. Serum albumin is a specific inhibitor of apoptosis in human endothelial cells. J. Cell Sci., 109(Pt 10):2571-2580.

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