Neuroprotective effect of lipoxin receptor agonist BML-111 on spinal cord ischemia-reperfusion injury in a rat model

doi:10.3969/j.issn.2095-4344.2016.18.009

Abstract

Abstract:

BACKGROUND: The mechanisms of spinal cord ischemia-reperfusion injury are the result of the combined effects of multiple factors, but there is no effective treatment.

OBJECTIVE: To investigate the effect of lipoxin receptor agonist BML-111 on inflammatory factor and apoptosis in rats with spinal cord ischemia-reperfusion injury.

METHODS: A total of 72 healthy adult male Sprague-Dawley rats were randomly divided into sham surgery group, ischemia-reperfusion group and BML-111 group. Rat models of spinal cord ischemia-reperfusion injury were established by clamping the abdominal aorta in the later two groups. Rats in the ischemia-reperfusion group and BML-111 group were injected with 0.1 mL of saline and 1 mg/kg BML-111 through caudal vein at 30 minutes after model establishment.

RESULTS AND CONCLUSION: Compared with ischemia-reperfusion group, BBB scores were significantly improved, pathological injury of spinal cord tissue significantly reduced, the number of apoptotic cells, tumor necrosis factor α and interleukin-1β expression, myeloperoxidase oxide activity and malondialdehyde content decreased in the BML-111 group. These findings indicate that lipoxin receptor agonist BML-111 can inhibit neuronal apoptosis and inflammation so as to reduce spinal cord injury.
中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

Key words: Spinal Cord Ischemia, Reperfusion Injury, Receptors, Lipoxin, Apoptosis

Ren Xiao-bo, Wang Gui-hua, Lu Tan, An Yong-bo, Liu Zhong-he, Dong Yu-zhen. Neuroprotective effect of lipoxin receptor agonist BML-111 on spinal cord ischemia-reperfusion injury in a rat model[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(18): 2642-2647.

Figures/Tables 5

References

[1] Zhang Q, Huang C, Meng B, et al. Acute effect of Ghrelin on ischemia/reperfusion injury in the rat spinal cord. Int J Mol Sci. 2012;13(8):9864-9876.

[2] Manzanero S, Santro T, Arumugam TV. Neuronal oxidative stress in acute ischemic stroke: sources and contribution to cell injury. Neurochem Int. 2013;62(5): 712-718.

[3] Li XQ, Lv HW, Tan WF, et al. Role of the TLR4 pathway in blood-spinal cord barrier dysfunction during the bimodal stage after ischemia/reperfusion injury in rats. J Neuroinflammation. 2014;11:62.

[4] Li XQ, Lv HW, Wang ZL, et al. MiR-27a ameliorates inflammatory damage to the blood-spinal cord barrier after spinal cord ischemia: reperfusion injury in rats by downregulating TICAM-2 of the TLR4 signaling pathway. J Neuroinflammation. 2015;12:25.

[5] Wolfrum S, Nienstedt J, Heidbreder M, et al. Calcitonin gene related peptide mediates cardioprotection by remote preconditioning. Regul Pept. 2005;127(1-3):217-224.

[6] Yamazaki M, Mochizuki M, Ikeda Y, et al. Clinical results of surgery for thoracic myelopathy caused by ossification of the posterior longitudinal ligament: operative indication of posterior decompression with instrumented fusion. Spine (Phila Pa 1976). 2006; 31(13):1452-1460.

[7] Wada T, Yao H, Miyamoto T, et al. Prevention and detection of spinal cord injury during thoracic and thoracoabdominal aortic repairs. Ann Thorac Surg. 2001;72(1):80-84; discussion 85.

[8] Gewirtz A. Lipoxin analogs: novel anti-inflammatory mediators. Curr Opin Investig Drugs. 2005;6(11): 1112-1115.

[9] Gilroy DW, Lawrence T, Perretti M, et al. Inflammatory resolution: new opportunities for drug discovery. Nat Rev Drug Discov. 2004;3(5):401-416.

[10] Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol. 2008;8(5):349-361.

[11] Petasis NA, Akritopoulou-Zanze I, Fokin VV, et al. Design, synthesis and bioactions of novel stable mimetics of lipoxins and aspirin-triggered lipoxins. Prostaglandins Leukot Essent Fatty Acids. 2005;73(3-4):301-321.

[12] Celic T, Španjol J, Bobinac M, et al. Mn porphyrin-based SOD mimic, MnTnHex-2-PyP(5+), and non-SOD mimic, MnTBAP(3-), suppressed rat spinal cord ischemia/reperfusion injury via NF-κB pathways. Free Radic Res. 2014;48(12):1426-1442.

[13] Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995;12(1):1-21.

[14] 于清波,邓剑锋,高大新,等.膝骨关节炎关节液中丙二醛、超氧化物歧化酶在玻璃酸钠注射前后的变化[J].中国组织工程研究,2014,18(46):7528-7532.

[15] 潘峰, 祝成亮,陶凤华,等.他克莫司后处理对缺血再灌注脊髓组织炎性反应的抑制作用[J].生物骨科材料与临床研究,2014,11(2):1-4.

[16] Zivin JA, DeGirolami U. Spinal cord infarction: a highly reproducible stroke model. Stroke. 1980;11(2):200-202.

[17] Picone AL, Green RM, Ricotta JR, et al. Spinal cord ischemia following operations on the abdominal aorta. J Vasc Surg. 1986;3(1):94-103.

[18] Walters BC, Hadley MN, Hurlbert RJ, et al. Guidelines for the management of acute cervical spine and spinal cord injuries: 2013 update. Neurosurgery. 2013; 60 Suppl 1:82-91.

[19] Bannenberg G, Serhan CN. Specialized pro-resolving lipid mediators in the inflammatory response: An update. Biochim Biophys Acta. 2010;1801(12):1260-1273.

[20] Lee TH, Lympany P, Crea AE, et al. Inhibition of leukotriene B4-induced neutrophil migration by lipoxin A4: structure-function relationships. Biochem Biophys Res Commun. 1991;180(3):1416-1421.

[21] Li HB, Wang GZ, Gong J, et al. BML-111 attenuates hemorrhagic shock-induced acute lung injury through inhibiting activation of mitogen-activated protein kinase pathway in rats. J Surg Res. 2013;183(2):710-719.

[22] Lopez MS, Dempsey RJ, Vemuganti R. Resveratrol neuroprotection in stroke and traumatic CNS injury. Neurochem Int. 2015;89:75-82.

[23] Gong G, Yuan LB, Hu L, et al. Glycyrrhizin attenuates rat ischemic spinal cord injury by suppressing inflammatory cytokines and HMGB1. Acta Pharmacol Sin. 2012;33(1):11-18.

[24] Izumi B, Nakasa T, Tanaka N, et al. MicroRNA-223 expression in neutrophils in the early phase of secondary damage after spinal cord injury. Neurosci Lett. 2011;492(2):114-118.