|
|
The protection of VGX-1027 on myocardial ischemia-reperfusion injury in mice cardiac transplantation |
DAI Juji1, ZHENG Xiangtao1, FU Hongxing2, ZHOU Mengtao1. |
1.Department of General Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015; 2.School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035
|
|
Cite this article: |
DAI Juji,ZHENG Xiangtao,FU Hongxing, et al. The protection of VGX-1027 on myocardial ischemia-reperfusion injury in mice cardiac transplantation[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2016, 46(3): 183-186.
|
|
Abstract Objective: To explore the effect of VGX-1027 on myocardial ischemia-reperfusion (MI/R) injury in mice cardiac transplantation. Methods: Forty mice were randomly divided into 2 groups: cardiac transplantation group and cardiac transplantation+VGX-1027 group (70 mg/kg). The grafts were collected at 24 h after cardiac transplantation. Histopathology was observed with haematoxylin-eosin staining. CD3+T cell, CD4+T cell and CD8+T cell infiltrated into cardiac grafts were detected by immunohistochemistry. Expression of caspase-3, Bax and Bcl-2 were determined with Western blotting, and cytokines expression of TNF-α, IL-1β and IL-6 were measured with ELISA. Results: Compared with cardiac transplantation group, mice treated with VGX-1027 exhibited significantly lower degree of leukocyte and myocyte necrosis. The infiltration of CD3+T cell, CD4+T cell and CD8+T cell in grafts were reduced with the treatmet of VGX-1027. The expression of caspase-3 and Bax was inhibited in cardiac transplantation+VGX-1027 group while the expression of Bcl-2 was increased. Furthermore, VGX-1027 pretreatment resulted in a decrease in serum cytokines of TNF-α, IL-1β and IL-6. Conclusion: VGX-1027 can significantly reduce ischemia-reperfusion injury in mice cervical cardiac transplantation model.
|
Received: 16 August 2015
|
|
|
|
|
[1] BARKER W H, MULLOOLY J P, GETCHELL W. Changing incidence and survival for heart failure in a well-defined older population, 1970-1974 and 1990-1994[J]. Circulation, 2006, 113(6): 799-805.
[2] KLOTZ S, SCHELD H H. Surgical approach to end-stage heart failure[J]. Curr Opin Anesthesio, 2011, 24(1): 86-91.
[3] BOROS P, BROMBERG J S. New cellular and molecular immune pathways in ischemia reperfusion injury[J]. Am JTransplant, 2006, 6(4): 652-658.
[4] FAGONE P, MUTHUMANI K, MANGANO K, et al. VGX-1027 modulates genes involved in lipopolysaccharide-induced Toll-like receptor 4 activation and in a murine model of systemic lupus erythematosus[J]. Immunology, 2014, 142(4): 594-602.
[5] SHIMAMOTO A,CHONG A J,YADA M, et al. Inhibition of Toll-like receptor 4 with eritoran attenuates myocardial ischemia-reperfusion injury[J]. Circulation, 2006, 114(1Suppl): I270-274.
[6] STOJANOVIC I, CUZZOCREA S, MANGANO K, et al. In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models[J]. Clin Immunol, 2007, 123(3): 311-323.
[7] MANGANO K, SARDESAI N Y, QUATTROCCHI C, et al.Effects of the immunomodulator, VGX-1027, in endotoxin induced uveitis in Lewis rats[J]. Brit J Pharmacol, 2008, 155(5): 722-730.
[8] SVENSSON E C, MARSHALL D J, WOODARD W, et al. Efficient and stable transduction of cardiomyocytes after intramyocardial injection or intracoronary perfusion with recombinant adeno-associated virus vectors[J]. Circulation, 1999, 99(2): 201-205.
[9] MATSUURA A, YASUURA K. Simplified mouse cervical heart transplantation using a cuff technique[J]. Transplantation, 1991, 51(4): 896-933.
[10] 冯剑锷, 孙宗全. 应用cuff技术建立小鼠异位心脏移植模型[J]. 中华实验外科杂志, 2005, 22(12): 1576-1577.
[11] FRANGOGIANNIS N G.The inflammatory response in myocardial injury, repair, and emodelling[J]. Nat Rev Cardiol, 2014, 11(5): 255-265.
[12] VINTEN-JOHANSEN J. Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury[J]. Cardiovasc Res, 2004, 61(3): 481-497.
|
|
|
|