
浏览全部资源
扫码关注微信
收稿:2019-11-25,
纸质出版:2020-03-30
移动端阅览
熊梅, 王霖邦, 聂丕明, 等. 曲克芦丁治疗脊髓损伤的转录组学研究[J]. 第三军医大学学报, 2020,42(6):624-631.
Mei XIONG, Linbang WANG, Piming NIE, et al. Protective effect of troxerutin against spinal cord injury in rats: a transcriptomic study[J]. Journal of Third Military Medical University, 2020, 42(6): 624-631.
熊梅, 王霖邦, 聂丕明, 等. 曲克芦丁治疗脊髓损伤的转录组学研究[J]. 第三军医大学学报, 2020,42(6):624-631. DOI: 10.16016/j.1000-5404.201910178.
Mei XIONG, Linbang WANG, Piming NIE, et al. Protective effect of troxerutin against spinal cord injury in rats: a transcriptomic study[J]. Journal of Third Military Medical University, 2020, 42(6): 624-631. DOI: 10.16016/j.1000-5404.201910178.
Objective
2
To investigate the protective effect of troxerutin against spinal cord injury (SCI) in rats and explore the underlying mechanisms.
Methods
2
Sixty 8-week-old male SD rats were randomly divided into sham operation group
SCI group and troxerutin treatment group. In the sham group
the rats were subjected to laminectomy without SCI; rat models of SCI were established in SCI group and troxerutin treatment group
and in the latter group
the rats received daily intravenous injection of troxerutin after SCI for 4 consecutive weeks. Neurological recovery of the rats was assessed based on the Basso-Beattie-Bresnehan (BBB) score
and HE staining was used to observe the changes in the vacuoles and blood vessels at the injury site of the spinal cord. RNA sequencing was used to examine the differential gene expressions in the injured spinal cord tissue between SCI group and troxerutin group
and Western blotting was performed to verify the differential expression of caspase-6 protein.
Results
2
Two weeks of troxerutin treatment significantly increased the BBB score of the rats as compared with the rats in SCI group (
P
<
0.05)
though the BBB scores in both groups were still lower than that in the sham operation group. At 4 weeks of treatment
the rats in troxerutin group showed decreased vacuoles with increased angiogenesis in the injured spinal cord tissues in comparison with the rats in SCI group. RNA sequencing showed that 261 genes were differentially expressed in the injured spinal cord tissue between troxerutin group and SCI group
including 217 up-regulated and 44 down-regulated genes. GO and KEGG enrichment analysis suggested that troxerutin was capable of activating several signaling pathways including the Wnt
Hippo
TGF-β and Apoptosis pathways
which were functionally related to apoptosis
angiogenesis
neuronal formation
and vasculature. The expression of caspase-6 protein in the semi-dark zone of the injured spinal cord tissues was significantly higher in SCI group than in troxerutin group (
P
<
0.05).
Conclusion
2
Troxerutin shows obvious protective effect against spinal cord injury in rats
possibly by inhibiting cell apoptosis and promoting angiogenesis in the injured spinal cord.
ALKABIE S BOILEAU A J The role of therapeutic hypothermia after traumatic spinal cord injury--a systematic review World Neurosurg 2016 86 432 449 10.1016/j.wneu.2015.09.079 ALKABIE S, BOILEAU A J. The role of therapeutic hypothermia after traumatic spinal cord injury--a systematic review. World Neurosurg, 2016, 86: 432-449. DOI: 10.1016/j.wneu.2015.09.079.
CHENG C LI X GAO S F Expression of CAPON after spinal cord injury in rats J Mol Neurosci 2008 34 2 109 119 10.1007/s12031-007-9019-5 CHENG C, LI X, GAO S F, et al . Expression of CAPON after spinal cord injury in rats. J Mol Neurosci, 2008, 34(2): 109-119. DOI: 10.1007/s12031-007-9019-5.
PIRAN S SCHULMAN S Incidence and risk factors for venous thromboembolism in patients with acute spinal cord injury: a retrospective study Thromb Res 2016 147 97 101 10.1016/j.thromres.2016.09.030 PIRAN S, SCHULMAN S. Incidence and risk factors for venous thromboembolism in patients with acute spinal cord injury: a retrospective study. Thromb Res, 2016, 147: 97-101. DOI: 10.1016/j.thromres.2016.09.030.
KWON B K TETZLAFF W GRAUER J N Pathophysiology and pharmacologic treatment of acute spinal cord injury Spine J 2004 4 4 451 464 10.1016/j.spinee.2003.07.007 KWON B K, TETZLAFF W, GRAUER J N, et al . Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J, 2004, 4(4): 451-464. DOI: 10.1016/j.spinee.2003.07.007.
齐 英娜 王 威 吴 鑫杰 脊髓损伤后微循环的变化及微循环障碍的药物治疗进展 中医正骨 2017 29 10 47 49 10.3969/j.issn.1001-6015.2017.10.009 齐英娜, 王威, 吴鑫杰, 等.脊髓损伤后微循环的变化及微循环障碍的药物治疗进展.中医正骨, 2017, 29 (10): 47-49. DOI: 10.3969/j.issn.1001-6015.2017.10.009.
QI Y N WANG W WU X J Changes of microcirculation after spinal cord injury and drug treatment progress of microcirculation disorders J Trad Chin Orthop Trauma 2017 29 10 47 49 10.3969/j.issn.1001-6015.2017.10.009 QI Y N, WANG W, WU X J, et al .Changes of microcirculation after spinal cord injury and drug treatment progress of microcirculation disorders. J Trad Chin Orthop Trauma, 2017, 29(10): 47-49. DOI: 10.3969/j.issn.1001-6015.2017.10.009.
JIA X F KOWALSKI R G SCIUBBA D M Critical care of traumatic spinal cord injury J Intens Care Med 2013 28 1 12 23 10.1177/0885066611403270 JIA X F, KOWALSKI R G, SCIUBBA D M, et al . Critical care of traumatic spinal cord injury. J Intens Care Med, 2013, 28(1): 12-23. DOI: 10.1177/0885066611403270.
LU J WU D M ZHENG Z H Troxerutin protects against high cholesterol-induced cognitive deficits in mice Brain 2011 134 Pt 3 783 797 10.1093/brain/awq376 LU J, WU D M, ZHENG Z H, et al . Troxerutin protects against high cholesterol-induced cognitive deficits in mice. Brain, 2011, 134(Pt 3): 783-797. DOI: 10.1093/brain/awq376.
QADIRI A MIRZAEI BAVIL F HAMIDIAN G Administration of troxerutin improves testicular function and structure in type-1 diabetic adult rats by reduction of apoptosis Avicenna J Phytomed 2019 9 4 374 385 QADIRI A, MIRZAEI BAVIL F, HAMIDIAN G, et al . Administration of troxerutin improves testicular function and s tructure in type-1 diabetic adult rats by reduction of apoptosis. Avicenna J Phytomed, 2019, 9(4): 374-385.
JAMALI-RAEUFY N KARDGAR S BALUCHNEJADMOJARAD T Troxerutin exerts neuroprotection against lipopolysaccharide (LPS) induced oxidative stress and neuroinflammation through targeting SIRT1/SIRT3 signaling pathway Metab Brain Dis 2019 34 5 1505 1513 10.1007/s11011-019-00454-9 JAMALI-RAEUFY N, KARDGAR S, BALUCHNEJADMOJARAD T, et al . Troxerutin exerts neuroprotection against lipopolysaccharide (LPS) induced oxidative stress and neuroinflammation through targeting SIRT1/SIRT3 signaling pathway. Metab Brain Dis, 2019, 34(5): 1505-1513. DOI: 10.1007/s11011-019-00454-9.
曹 婉鑫 唐 瑶 陈 洋 曲克芦丁药理作用的研究进展 中国食物与营养 2015 21 9 73 75 10.3969/j.issn.1006-9577.2015.09.020 曹婉鑫, 唐瑶, 陈洋.曲克芦丁药理作用的研究进展.中国食物与营养, 2015, 21(9): 73-75. DOI: 10.3969/j.issn.1006-9577.2015.09.020.
CAO W X TANG Y CHEN Y Research advancement of pharmacological function of troxerutin Food Nutr China 2015 21 9 73 75 10.3969/j.issn.1006-9577.2015.09.020 CAO W X, TANG Y, CHEN Y. Research advancement of pharmacological function of troxerutin. Food Nutr China, 2015, 21(9): 73-75. DOI: 10.3969/j.issn.1006-9577.2015.09.020.
程 素利 徐 家淳 王 剑歌 急性脊髓损伤大鼠Allen's造模方法的改良及行为学评价 四川中医 2015 33 10 43 45 http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=sczy201510021 程素利, 徐家淳, 王剑歌, 等.急性脊髓损伤大鼠Allen's造模方法的改良及行为学评价.四川中医, 2015, 33(10): 43-45.
CHENG S L XU J C WANG J G Improvement of Allen's modeling method in rats with acute spinal cord injury and Behavioral evaluation J Sichuan Tradit Chin Med 2015 33 10 43 45 http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=sczy201510021 CHENG S L, XU J C, WANG J G, et al . Improvement of Allen's modeling method in rats with acute spinal cord injury and Behavioral evaluation. J Sichuan Tradit Chin Med, 2015, 33(10): 43-45.
BYRNES K R STOICA B A FRICKE S Cell cycle activation contributes to post-mitotic cell death and secondary damage after spinal cord injury Brain 2007 130 Pt 11 2977 2992 10.1093/brain/awm179 BYRNES K R, STOICA B A, FRICKE S, et al . Cell cycle activation contributes to post-mitotic cell death and secondary damage after spinal cord injury. Brain, 2007, 130(Pt 11): 2977-2992. DOI: 10.1093/brain/awm179.
GROSSMAN S D WOLFE B B YASUDA R P Alterations in AMPA receptor subunit expression after experimental spinal cord contusion injury J Neurosci 1999 19 14 5711 5720 http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=db83b330eaa68703a9bc2ddbb4832fe2 GROSSMAN S D, WOLFE B B, YASUDA R P, et al . Alterations in AMPA receptor subunit expression after experimental spinal cord contusion injury. J Neurosci, 1999, 19(14): 5711-5720.
BASSO D M BEATTIE M S BRESNAHAN J C A sensitive and reliable locomotor rating scale for open field testing in rats J Neurotrauma 1995 12 1 1 21 10.1089/neu.1995.12.1 BASSO D M, BEATTIE M S, BRESNAHAN J C. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma, 1995, 12(1): 1-21. DOI: 10.1089/neu.1995.12.1.
National Spinal Cord Injury Statistical Center Spinal cord injury facts and figures at a glance J Spinal Cord Med 2014 37 3 355 356 http://d.old.wanfangdata.com.cn/OAPaper/oai_pubmedcentral.nih.gov_3555099 National Spinal Cord Injury Statistical Center. Spinal cord injury facts and figures at a glance. J Spinal Cord Med, 2014, 37(3): 355-356.
杨 盛林 罗 春山 脊髓缺血再灌注损伤后脊髓微循环的血流动力学改变 哈尔滨医药 2019 39 3 293 295 http://d.old.wanfangdata.com.cn/Periodical/hebyy201903050 杨盛林, 罗春山.脊髓缺血再灌注损伤后脊髓微循环的血流动力学改变.哈尔滨医药, 2019, 39(3): 293-295.
YANG S L LUO C S The hemodynamic changes of spinal cord microcirculation after spinal cord ischemic reperfusion injury Harbin Med J 2019 39 3 293 295 http://d.old.wanfangdata.com.cn/Periodical/hebyy201903050 YANG S L, LUO C S. The hemodynamic changes of spinal cord microcirculation after spinal cord ischemic reperfusion injury. Harbin Med J, 2019, 39(3): 293-295.
曾 静 王 茹 李 丹丹 曲克芦丁脑蛋白水解物对大脑中动脉栓塞后大鼠神经血管单元的保护作用 中国卒中杂志 2017 12 12 1097 1103 10.3969/j.issn.1673-5765.2017.12.006 曾静, 王茹, 李丹丹, 等.曲克芦丁脑蛋白水解物对大脑中动脉栓塞后大鼠神经血管单元的保护作用.中国卒中杂志, 2017, 12(12): 1097-1103. DOI: 10.3969/j.issn.1673-5765.2017.12.006.
ZENG J WANG R LI D D Protective effect of troxerutin and cerebroprotein hydrolysate on neurovascular unit in rats after middle cerebral artery occlusion Chin J Stroke 2017 12 12 1097 1103 10.3969/j.issn.1673-5765.2017.12.006 ZENG J, WANG R, LI D D, et al . Protective effect of troxerutin and cerebroprotein hydrolysate on neurovascular unit in rats after middle cerebral artery occlusion. Chin J Stroke, 2017, 12(12): 1097-1103. DOI: 10.3969/j.issn.1673-5765.2017.12.006.
WANG T ZHENG L WANG Q Emerging roles and mechanisms of FOXC2 in cancer Clin Chim Acta 2018 479 84 93 10.1016/j.cca.2018.01.019 WANG T, ZHENG L, WANG Q, et al . Emerging roles and mechanisms of FOXC2 in cancer. Clin Chim Acta, 2018, 479: 84-93. DOI: 10.1016/j.cca.2018.01.019 .
LIN R Z MELERO-MARTIN J M Fibroblast growth factor-2 facilitates rapid anastomosis formation between bioengineered human vascular networks and living vasculature Methods 2012 56 3 440 451 10.1016/j.ymeth.2012.01.006 LIN R Z, MELERO-MARTIN J M. Fibroblast growth factor-2 facilitates rapid anastomosis formation between bioengineered human vascular networks and living vasculature. Methods, 2012, 56(3): 440-451. DOI: 10.1016/j.ymeth.2012.01.006.
ZHAO H LIU Y ZENG J Troxerutin and cerebroprotein hydrolysate injection protects neurovascular units from oxygen-glucose deprivation and reoxygenation-induced injury in vitro Evid Based Complement Alternat Med 2018 2018 9859672 10.1155/2018/9859672 ZHAO H, LIU Y, ZENG J, et al . Troxerutin and cerebroprotein hydrolysate injection protects neurovascular units from oxygen-glucose deprivation and reoxygenation-induced injury in vitro. Evid Based Complement Alternat Med, 2018, 2018: 9859672. DOI: 10.1155/2018/9859672.
刘 春华 刘 捷 神经元凋亡与Caspase家族及细胞周期研究进展 人民军医 2018 61 7 641 644 http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=rmjy201807023 刘春华, 刘捷.神经元凋亡与Caspase家族及细胞周期研究进展.人民军医, 2018, 61(7): 641-644.
LIU C H LIU J Research progress on neuronal apoptosis, caspase family and cell cycle People Mil Surg 2018 61 7 641 644 http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=rmjy201807023 LIU C H, LIU J.Research progress on neuronal apoptosis, caspase family and cell cycle. People Mil Surg, 2018, 61(7): 641-644.
GAO K SHEN Z L YUAN Y J Simvastatin inhibits neural cell apoptosis and promotes locomotor recovery via activation of Wnt/β-catenin signaling pathway after spinal cord injury J Neurochem 2016 138 1 139 149 10.1111/jnc.13382 GAO K, SHEN Z L, YUAN Y J, et al . Simvastatin inhibits neural cell apoptosis and promotes locomotor recovery via activation of Wnt/β-catenin signaling pathway after spinal cord injury. J Neurochem, 2016, 138(1): 139-149. DOI: 10.1111/jnc.13382.
SUMIDA Y KAMEI N SUGA N The endoplasmic Reticulum stress transducer old astrocyte specifically induced substance positively regulates glial scar formation in spinal cord injury Neuroreport 2018 29 17 1443 1448 10.1097/WNR.0000000000001128 SUMIDA Y, KAMEI N, SUGA N, et al . The endoplasmic Reticulum stress transducer old astrocyte specifically induced substance positively regulates glial scar formation in spinal cord injury. Neuroreport, 2018, 29(17): 1443-1448. DOI: 10.1097/WNR.0000000000001128.
江 玲军 陈 之瑜 叶 嘉靖 丁苯酞对脊髓损伤大鼠神经运动功能的保护作用及机制研究 中国临床药理学杂志 2019 35 16 1765 1769 10.13699/j.cnki.1001-6821.2019.16.013 江玲军, 陈之瑜, 叶嘉靖, 等.丁苯酞对脊髓损伤大鼠神经运动功能的保护作用及机制研究.中国临床药理学杂志, 2019, 35(16): 1765-1769. DOI: 10.13699/j.cnki.1001-6821.2019.16.013.
JIANG L J CHEN Z Y YE J J Protective effect and mechanism of butylphthalide on spinal cord injury rats Chin J Clin Pharmacol 2019 35 16 1765 1769 10.13699/j.cnki.1001-6821.2019.16.013 JIANG L J, CHEN Z Y, YE J J, et al . Protective effect and mechanism of butylphthalide on spinal cord injury rats. Chin J Clin Pharmacol, 2019, 35(16): 1765-1769. DOI: 10.13699/j.cnki.1001-6821.2019.16.013.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621