Experimental Study of Remifentanil-poly-caprolactone Infusion through Abdominal Aorta against Spinal Cord Ischemia-Reperfusion Injury_Journal of Biomedical Engineering

Authors：

1. Department of Anesthesiology, Guizhou Provincial People's Hospital, Guiyang 550002, China;
2. Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu 610041, China;
3. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

Keywords：

remifentanil-poly-caprolactone; spinal cord ischemia reperfusion injury; mitochondria; spinal cord microcirculation

DOI：

10.7507/1001-5515.20160120

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The present study was to investigate the effects of infusing remifentanil-poly-caprolactone (REM-PCL) through the abdominal aorta on spinal cord ischemia reperfusion injury (SCIRI). The model of SCIRI was created by clamping the infrarenal aortic in thirty-six New Zealand white rabbits, which were randomly divided into sham group (group S), control group (group C), and REM-PCL group (group R) with 12 rabbits in each one. The spinal cord microcirculatory blood flow (SCMBF) and blood flow rate (BFR) were monitored before ischemia, 15 min, 30 min, 60 min and 120 min after reperfusion, respectively. Neurologic Function was evaluated before ischemia, 6h, 12h and 24h after reperfusion. The concentration of serum neuron-specific enolase (NSE), interleukin-lβ (IL-lβ) and interleukin-8 (IL-8) were monitored before ischemia, 45 min after ischemia, 30 min, 60 min, 6 h, 12 h and 24 h after reperfusion. The abnormal rate of motor neuron of spinal cord tissues and the level of superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), total anti-oxidation capacity (T-AOC) and mitochondrial swelling degree (MSD) in neural mitochondria were determined before ischemia, 45 min after clamping, 60 min and 120 min after reperfusion. As a result, the neural mitochondrial SOD, GSH-PX and T-AOC decreased while ROS, MDA, MSD, IL-lβ, IL-8 and NSE distinctly increased after clamping of the abdominal aorta as compared to the value before ischemia in group C (P < 0.01). Neurologic function scores recovered more rapidly in group R than those in group C during reperfusion (P < 0.01). The neural mitochondrial SOD, GSH-PX and T-AOC were distinctly higher while ROS, MDA, MSD, IL-lβ, IL-8 and NSE were distinctly lower in group R than those in group C (P < 0.01). The abnormal rate of motor neuron was significantly higher in group C during reperfusion than that in group R (P < 0.01). It has been shown that the intra-aortic REM-PCL infusion can alleviate SCIRI by inhibiting inflammatory response and improving mitochondrial anti-oxidation capacity.

Citation： FANGHua, LIHuafeng, ZHANGWeijing, YANGMiao, ZHANGFangxiang, ZHANGJianping, WANGQuanyun, WANGRurong, LIUJin. Experimental Study of Remifentanil-poly-caprolactone Infusion through Abdominal Aorta against Spinal Cord Ischemia-Reperfusion Injury. Journal of Biomedical Engineering, 2016, 33(4): 735-740. doi: 10.7507/1001-5515.20160120 Copy

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2.	章建平, 方华, 杨淼, 等.天麻素对脊髓缺血再灌注损伤中脊髓微循环血流量的影响[J].中国实验方剂学杂志, 2015, 21(16):128-133.
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9.	FENG Xudong, XIA Qing, YUAN Lan, et al. Impaired mitochondrial function and oxidative stress in rat cortical neurons:implications for gadolinium-induced neurotoxicity[J]. Neurotoxicology, 2010, 31(4):391-398.
10.	MA Shuwei, LIU Xingyan, XUN Qingrui, et al. Neuroprotective effect of Ginkgolide K against H₂O₂-induced PC12 cell cytotoxicity by ameliorating mitochondrial dysfunction and oxidative stress[J]. Biol Pharm Bull, 2014, 37(2):217-225.
11.	JIANG Daixun, LU Zhisong, LI Gebin, et al. Electroacupuncture improves microcirculation and neuronal morphology in the spinal cord of a rat model of intervertebral disc extrusion[J]. Neural Regen Res, 2015, 10(2):237-243.
12.	BADEM S, UGURLUCAN M, EL H, et al. Effects of ginkgo biloba extract on spinal cord ischemia-reperfusion injury in rats[J]. Ann Vasc Surg, 2014, 28(5):1296-1305.
13.	BLASER A, LANG J, HENKE D, et al. Influence of durotomy on laser-Doppler measurement of spinal cord blood flow in chondrodystrophic dogs with thoracolumbar disk extrusion[J]. Vet Surg, 2012, 41(2):221-227.
14.	KURTOGLU T, BASOGLU H, OZKISACIK E A, et al. Effects of cilostazol on oxidative stress, systemic cytokine release, and spinal cord injury in a rat model of transient aortic occlusion[J]. Ann Vasc Surg, 2014, 28(2):479-488.
15.	IGOUDJIL A, MAGRANÉ J, FISCHER L R, et al. In vivo pathogenic role of mutant SOD1 localized in the mitochondrial intermembrane space[J]. J Neurosci, 2011, 31(44):15826-15837.
16.	VISAVADIYA N P, PATEL S P, VANROOYEN J L, et al. Cellular and subcellular oxidative stress parameters following severe spinal cord injury[J]. Redox Biol, 2015, 8:59-67.
17.	LI Haotian, JIA Zhiqiang, LI Gang, et al. Neuroprotective effects of exendin-4 in rat model of spinal cord injury via inhibiting mitochondrial apoptotic pathway[J]. Int J Clin Exp Pathol, 2015, 8(5):4837-4843.
18.	BRECKWOLDT M O, PFISTER F M, BRADLEY P M, et al. Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo[J]. Nat Med, 2014, 20(5):555-560.
19.	CUI Y, ZHANG H, JI M, et al. Hydrogen-rich saline attenuates neuronal ischemia——reperfusion injury by protecting mitochondrial function in rats[J]. J Surg Res, 2014, 192(2):564-572.
20.	JU Chuanxia, HOU Lin, SUN Fusheng, et al. Anti-oxidation and antiapoptotic effects of chondroitin sulfate on 6-hydroxydopamine-induced injury through the up-regulation of Nrf2 and inhibition of mitochondria-mediated pathway[J]. Neurochem Res, 2015, 40(7):1509-1519.
21.	YE Bin, KROBOTH S L, PU Jielin, et al. Molecular identification and functional characterization of a mitochondrial sulfonylurea receptor 2 splice variant generated by intraexonic splicing[J]. Circ Res, 2009, 105(11):1083-1093.
22.	KIM J M, JANG Y H, KIM J. Morphine and remifentanil-induced cardioprotection:its experimental and clinical outcomes[J]. Korean J Anesthesiol, 2011, 61(5):358-366.
23.	方华, 杨淼, 张伟晶, 等.REM-PCL对犬缺血再灌注心肌线粒体抗氧化能力的影响[J].中国医学创新, 2015, 12(21):16-18.

1. ZHOU Y F, LI L, FENG F, et al. Osthole attenuates spinal cord ischemia-reperfusion injury through mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction in rats[J]. J Surg Res, 2013, 185(2):805-814.
2. 章建平, 方华, 杨淼, 等.天麻素对脊髓缺血再灌注损伤中脊髓微循环血流量的影响[J].中国实验方剂学杂志, 2015, 21(16):128-133.
3. 四川大学华西医院.一种瑞芬太尼高分子缓释镇痛药物及其制备方法:中国, CN200810045272.8[P].2008-07-16.
4. 方华, 章建平, 张竞超, 等.REM-PCL对脊髓缺血再灌注损伤中运动诱发电位的影响[J].中国医院药学杂志, 2015, 35(12):5-11.
5. 方华, 章建平, 张竞超, 等.经腹主动脉灌注瑞芬太尼聚己内酯对脊髓缺血再灌注损伤中脊髓能量代谢的影响[J].中国医院药学杂志, 2015, 35(15):1388-1393.
6. NAZLI Y, COLAK N, NAMUSLU M, et al. Cilostazol attenuates spinal cord ischemia-reperfusion injury in rabbits[J]. J Cardiothorac Vasc Anesth, 2015, 29(2):351-359.
7. GVRER B, KERTMEN H, KASIM E, et al. Neuroprotective effects of testosterone on ischemia/reperfusion injury of the rabbit spinal cord[J]. Injury, 2015, 46(2):240-248.
8. ILHAN G, AKSUN M, OZPAK B, et al. The effect of combined hyperbaric oxygen and iloprost treatment on the prevention of spinal cord ischaemia-reperfusion injury:an experimental study[J]. Eur J Cardiothorac Surg, 2013, 44(5):e332-e340.
9. FENG Xudong, XIA Qing, YUAN Lan, et al. Impaired mitochondrial function and oxidative stress in rat cortical neurons:implications for gadolinium-induced neurotoxicity[J]. Neurotoxicology, 2010, 31(4):391-398.
10. MA Shuwei, LIU Xingyan, XUN Qingrui, et al. Neuroprotective effect of Ginkgolide K against H₂O₂-induced PC12 cell cytotoxicity by ameliorating mitochondrial dysfunction and oxidative stress[J]. Biol Pharm Bull, 2014, 37(2):217-225.
11. JIANG Daixun, LU Zhisong, LI Gebin, et al. Electroacupuncture improves microcirculation and neuronal morphology in the spinal cord of a rat model of intervertebral disc extrusion[J]. Neural Regen Res, 2015, 10(2):237-243.
12. BADEM S, UGURLUCAN M, EL H, et al. Effects of ginkgo biloba extract on spinal cord ischemia-reperfusion injury in rats[J]. Ann Vasc Surg, 2014, 28(5):1296-1305.
13. BLASER A, LANG J, HENKE D, et al. Influence of durotomy on laser-Doppler measurement of spinal cord blood flow in chondrodystrophic dogs with thoracolumbar disk extrusion[J]. Vet Surg, 2012, 41(2):221-227.
14. KURTOGLU T, BASOGLU H, OZKISACIK E A, et al. Effects of cilostazol on oxidative stress, systemic cytokine release, and spinal cord injury in a rat model of transient aortic occlusion[J]. Ann Vasc Surg, 2014, 28(2):479-488.
15. IGOUDJIL A, MAGRANÉ J, FISCHER L R, et al. In vivo pathogenic role of mutant SOD1 localized in the mitochondrial intermembrane space[J]. J Neurosci, 2011, 31(44):15826-15837.
16. VISAVADIYA N P, PATEL S P, VANROOYEN J L, et al. Cellular and subcellular oxidative stress parameters following severe spinal cord injury[J]. Redox Biol, 2015, 8:59-67.
17. LI Haotian, JIA Zhiqiang, LI Gang, et al. Neuroprotective effects of exendin-4 in rat model of spinal cord injury via inhibiting mitochondrial apoptotic pathway[J]. Int J Clin Exp Pathol, 2015, 8(5):4837-4843.
18. BRECKWOLDT M O, PFISTER F M, BRADLEY P M, et al. Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo[J]. Nat Med, 2014, 20(5):555-560.
19. CUI Y, ZHANG H, JI M, et al. Hydrogen-rich saline attenuates neuronal ischemia——reperfusion injury by protecting mitochondrial function in rats[J]. J Surg Res, 2014, 192(2):564-572.
20. JU Chuanxia, HOU Lin, SUN Fusheng, et al. Anti-oxidation and antiapoptotic effects of chondroitin sulfate on 6-hydroxydopamine-induced injury through the up-regulation of Nrf2 and inhibition of mitochondria-mediated pathway[J]. Neurochem Res, 2015, 40(7):1509-1519.
21. YE Bin, KROBOTH S L, PU Jielin, et al. Molecular identification and functional characterization of a mitochondrial sulfonylurea receptor 2 splice variant generated by intraexonic splicing[J]. Circ Res, 2009, 105(11):1083-1093.
22. KIM J M, JANG Y H, KIM J. Morphine and remifentanil-induced cardioprotection:its experimental and clinical outcomes[J]. Korean J Anesthesiol, 2011, 61(5):358-366.
23. 方华, 杨淼, 张伟晶, 等.REM-PCL对犬缺血再灌注心肌线粒体抗氧化能力的影响[J].中国医学创新, 2015, 12(21):16-18.

Journal of Biomedical Engineering

Experimental Study of Remifentanil-poly-caprolactone Infusion through Abdominal Aorta against Spinal Cord Ischemia-Reperfusion Injury

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