Protective effect of remote ischemic preconditioning on spinal cord ischemia reperfusion injury and its possible mechanism in a rabbit model
YU Qijing1 TIAN Wenhua2 YANG Yunzhao1
1.Department of Anesthesiology, Renmin Hospital of Wuhan University, Hubei Province, Wuhan 430060, China;
2.Department of Anesthesiology, Wuhan Hospital of Traditional Chinese Medicine, Hubei Province, Wuhan 430000, China
Abstract:Objective To investigate the protective effect of remote ischemic preconditioning (RIPC) on spinal cord ischemia reperfusion injury (SCIRI) and its possible mechanism in a rabbit model. Methods Thirty-six rabbits were randomly divided into sham operation group (Sham group), ischemia reperfusion group (IR group), IR+ RIPC group, 12 rats in each group. On the 2 sec and 5th day after reperfusion, 6 animals were sacrificed respectively. Animals in Sham group were exposed abdominal aorta (without interruption), IR group and IR+RIPC group received abdominal aortic clamp 30 min, and established SCIRI model. IR + RIPC group underwent RIPC before aortic clamp 1 h. All animals were evaluated for hindlimb function scores in postoperative 2 days and 5 days, according to the Tarlov standard, and then were sacrificed and the L3 - L5 segment of the spinal cord were detected to observe the pathological changes of spinal cord tissues. Meanwhile, the SOD1 activity and the expression level of SOD1 mRNA were detected. Results On the same timepoint, compared with the Sham group, the neurological function scores and pathological grading of spinal cord tissue in IR group were significantly decreased (P < 0.01), but compared with the IR group, the neurological function scores and pathological grading of spinal cord tissue in IR+ RIPC group were significantly improved (P < 0.01). On the second day after operation, compared with the Sham group, the activity of SOD1 and the expression level of SOD1 mRNA in the IR+RIPC group were all significantly increased (P < 0.01), whereas there was no significant change in the IR group (P > 0.05). On the 5th day after operation, compared with the Sham group, the activity of SOD1 and the expression level of SOD1 mRNA in the IR group were all significantly decreased (P < 0.01), and there was no significant change in the IR+RIPC group (P > 0.05). Compared with IR group, the SOD1 activity and the expression level of SOD1 mRNA were all significantly increased in the RIPC group (P < 0.01). The change of SOD1 mRNA expression in spinal cord was positively related to the change of SOD1 activity in IR group or IR+ RIPC group (R=0. 96 or 0.97, all P < 0.01). Conclusion RIPC has a certain preventive effect on rabbit SCIRI, and its mechanism is related to enhancing the expression of SOD1 in ischemic region of spinal cord tissues.
余奇劲1 田文华2 杨云朝1. 远程缺血预处理对兔脊髓缺血再灌注损伤的保护作用及其机制[J]. 中国医药导报, 2018, 15(9): 8-12.
YU Qijing1 TIAN Wenhua2 YANG Yunzhao1. Protective effect of remote ischemic preconditioning on spinal cord ischemia reperfusion injury and its possible mechanism in a rabbit model. 中国医药导报, 2018, 15(9): 8-12.
[1] 徐正虎,王君.阿托伐他汀预处理和缺血预处理对大鼠脑缺血再灌注损伤的保护作用[J].中华老年心脑血管病杂志,2015,17(3):310-312.
[2] 许垚,丁峰.缺血预处理在急性肾损伤中的应用进展[J].实用医学杂志,2017,33(21):3507-3510.
[3] Veighey K,Macallister R. Clinical applications of remote ischaemic preconditioning in native and transplant acute kidney injury [J]. Pediatr Nephrol,2015,30(10):1749-1759.
[4] Yu QJ,Wang YL,Zhou QS,et al. Effect of repetitive ischemic preconditioning on spinal cord ischemia in a rabbit model [J]. Life Sci,2006,79(15):1479-1483.
[5] Naslund TC,Hollier LH,Money SR,et al. Histopathological classification of spinal cord [J]. Ann Surg. 1992,215(5):409-415.
[6] Zhu P,Li JX,Fujino M,et al. Development and treatments of inflammatory cells and cytokines in spinal cord ischemia-reperfusion injury [J]. Mediators Inflamm,2013,2013(4):701-970.
[7] Panthee N,Ono M. Spinal cord injury following thoracic and thoracoabdominal aortic repairs [J]. Asian Cardiovasc Thorac Ann,2015,23(2):235-246.
[8] 卢光奎,余奇劲,何绮月.丙泊酚与主动脉阻断引起的脊髓缺血-再灌注损伤[J].医药导报,2011,30(6):770-772.
[9] Yu Q,Huang J,Hu J,et al. Advance in spinal cord ischemia reperfusion injury:Blood-spinal cord barrier and remote ischemic preconditioning [J]. Life Sci,2016,15(16):30193-30195.
[10] Drinkwater SL,Goebells A,Haydar A,et al. The Incidence of Spinal Cord Ischaemia Following Thoracic and Thoracoabdominal Aortic Endovascular Intervention [J]. Eur J Vasc Endovasc,2010,40(6):729-735.
[11] McCord JM,Edeas MA. Sod,Oxidative Stress and Human Pathologies:A Brief History and a Future Vision [J]. Biomed Pharmacother,2005,59(4):139-142.
[12] Fridovich I. Superoxide Anion Radical(O2-),Superoxide Dismutases,and Related Matters [J]. J Biol Chem,1997, 272(30):18515-18517.
[13] Sasaki T,Shimizu T,Koyama T,et al. Superoxide Dismutase De?ciency Enhances Superoxide Levels in Brain Tissues During Oxygenation and Hypoxia-Reoxygenation [J]. J Neurosci Res,2011,89(4):601-610.
[14] Ji H,Miao J,Zhang X,et al. Inhibition of sonic hedgehog signaling aggravates brain damage associated with the down-regulation of Gli1,Ptch1 and SOD1 expression in acute ischemic stroke [J]. Neurosci Lett,2012,506(1):1-6.
[15] Deshayes S,Heitz A,Morris MC,el al. Insight into the mechanism of internalization of the cell penetrating carrier peptide Pep-1 through conformational analysis [J]. Biochemistry,2004,43(6):1449-1457.
[16] Eum WS,Kim DW,Hwang IK,et al. In vivo protein transduction:biologically active intact pep-1-superoxide dismutase fusion protein efficiently protects against ischemic insult [J]. Free Radic Biol Med,2004,37(10):1656-1669.
[17] Yune TY,Lee JY,Jiang MH,et al. Systemic administration of PEP-1-SOD1 fusion protein improves functional recovery by inhibition of neuronal cell death after spinal cord injury [J]. Free Radic Biol Med,2008,45(8):1190-1200.
[18] Kim W,Kim DW,Yoo DY,et al. Neuroprotective effects of PEP-1-Cu,Zn-SOD against ischemic neuronal damage in the rabbit spinal cord [J]. Neurochem Res,2012, 37(2):307-313.
[19] Zhang YE,Wang JN,Tang JM,et al. In vivo protein transduction:delivery of PEP-1-SOD1 fusion protein into myocardium efficiently protects against ischemic insult [J]. Mol Cells,2009,27(2):159-166.
[20] Yu QJ,Yang Y. Function of SOD1,SOD2,and PI3K/AKT signaling pathways in the protection of propofol on spinal cord ischemic reperfusion injury in a rabbit model [J]. Life Sci,2016,1481():86-92. doi:10.1016/j.lfs.2016. 02.005. Epub 2016 Feb 3.
[21] Xia ZY,Huang ZY,Ansley DM. Large-Dose Propofol during Cardiopulmonary Bypass Decreases Biochemical Markers of Myocardial Injury in Coronary Surgery Patients:A Comparison with Isoflurane [J]. Anesth Analg,2006,103(3):527-532.