|本期目录/Table of Contents|

[1]彭程,黄健华,孙建忠,等.miR-126对急性脊髓损伤大鼠血管的作用及机制研究[J].国际骨科学杂志,2020,06:382-388.
　PENG Cheng,HUANG Jianhua,SUN Jianzhong,et al.miR-126 promotes angiogenesis in rats with acute spinal cord injury via upregulation of vascular endothelial growth factor[J].International Journal of Orthopaedics,2020,06:382-388.
点击复制

miR-126对急性脊髓损伤大鼠血管的作用及机制研究(PDF)

《国际骨科学杂志》[ISSN:1673-7083/CN:31-1952/R]

期数:
2020年06期
页码:
382-388
栏目:
基础研究
出版日期:
2020-12-20

文章信息/Info

Title:
miR-126 promotes angiogenesis in rats with acute spinal cord injury via upregulation of vascular endothelial growth factor
作者:
彭程; 黄健华; 孙建忠; 吴小建; 庄伟康; 石晓兵
201999, 上海市宝山区中西医结合医院骨科
Author(s):
PENG Cheng;  HUANG Jianhua;  SUN Jianzhong;  WU Xiaojian;  ZHUANG Weikang;  SHI Xiaobing.
Department of Orthopedics, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 201999, China
关键词:
急性脊髓损伤;  miR-126;  血管内皮生长因子
Keywords:
Acute spinal cord injury;  miR-126;  Vascular endothelial growth factor
分类号:
-
DOI:
10.3969/j.issn.1673-7083.2020.06.013
文献标识码:
A
摘要:
目的 探讨miR-126对急性脊髓损伤(ASCI)的调控作用及分子学机制。方法 80只雄性SD大鼠随机分为4组:模型组、阴性对照组、miR-126过表达组和miR-126沉默组,每组各20只。各组大鼠均采用改良的Allen's 打击法构建ASCI模型,30 min后模型组鞘内注射生理盐水,阴性对照组、miR-126过表达组和miR-126沉默组分别注射等量的agomiRNA阴性对照、agomiR-126和antagomiR-126,周期为14 d。采用Basso-Beattie-Bresnahan(BBB)运动功能评分法评价大鼠后肢运动能力,HE染色观察脊髓组织病理形态学,实时荧光定量聚合酶链式反应(PCR)检测miR-126和血管内皮生长因子(VEGF)基因表达量,蛋白免疫印迹法(Western blot)检测VEGF蛋白表达量,荧光免疫组化检测VEGF表达和分布,应用免疫组化SABC法染色脊髓组织Ⅷ因子相关抗原并观察血管生成情况,采用Targetscan数据库预测miR-126的靶基因和双荧光素酶检测miR-126与VEGF结合情况。结果 BBB运动功能评分结果显示,4组大鼠后肢运动功能随着时间增长均有不同程度的变化,模型组和阴性对照组BBB运动功能评分显著低于miR-126过表达组(P<0.05),明显高于miR-126沉默组(P<0.05),而模型组与阴性对照组之间差异无统计学意义(P>0.05)。HE染色结果显示,模型组、阴性对照组和miR-126沉默组脊髓组织内出血,疏松水肿,神经纤维消失,而miR-126过表达组脊髓恢复明显,组织水肿减轻,结构排列较完整。与模型组和阴性对照组比较,miR-126过表示组miR-126和VEGF基因表达量显著增加(P<0.05),在脊髓组织分布较密集且损伤区域脊髓灰质腹侧角内微血管数目明显增加(P<0.05),而miR-126过表示组miR-126和VEGF基因表达量显著减少(P<0.05),在脊髓组织分布较疏松且微血管数目明显减少(P<0.05)。Targetscan数据库预测VEGF是miR-126靶基因。双荧光素酶报告实验检测结果显示,VEGF与miR-126相结合。结论 miRNA-126可通过作用于靶基因VEGF,促进新生血管形成,从而改善大鼠ASCI。
Abstract:
Objective To investigate the effect of miR-126 on rats with acute spinal cord injury(ASCI)and its potential mechanism.Methods A total of 80 male SD rats were divided randomly into four groups: model group, negative control group, miR-126 overexpression gr

参考文献/References

[1] Galeiras Vázquez R, Ferreiro Velasco ME, Mourelo Farina M, et al. Update on traumatic acute spinal cord injury. Part 1[J]. Med Intensiva, 2017, 41(4): 237-247.
[2] Haque A, Ray SK, Cox A, et al. Neuron specific enolase: a promising therapeutic target in acute spinal cord injury[J]. Metab Brain Dis, 2016, 31(3): 487-495.
[3] Ni S, Cao Y, Jiang L, et al. Synchrotron radiation imaging reveals the role of estrogen in promoting angiogenesis after acute spinal cord injury in rats[J]. Spine(Phila Pa 1976), 2018, 43(18): 1241-1249.
[4] Orr MB, Gensel JC. Spinal cord injury scarring and inflammation: therapies targeting glial and inflammatory responses[J]. Neurotherapeutics, 2018, 15(3): 541-553.
[5] Sun P, Liu DZ, Jickling GC, et al. MicroRNA-based therapeutics in central nervous system injuries[J]. J Cereb Blood Flow Metab, 2018, 38(7): 1125-1148.
[6] Zhang T, Ni S, Luo Z, et al. The protective effect of microRNA-21 in neurons after spinal cord injury[J]. Spinal Cord, 2019, 57(2): 141-149.
[7] Long HQ, Li GS, Cheng X, et al. Role of hypoxia-induced VEGF in blood-spinal cord barrier disruption in chronic spinal cord injury[J]. Chin J Traumatol, 2015, 18(5): 293-295.
[8] Wang L, Lee AY, Wigg JP, et al. miR-126 regulation of angiogenesis in age-related macular degeneration in CNV mouse model[J]. Int J Mol Sci, 2016, 17(6): 895.
[9] Sweis R, Biller J. Systemic complications of spinal cord injury[J]. Curr Neurol Neurosci Rep, 2017, 17(2): 8.
[10] Herrera JJ, Sundberg LM, Zentilin L, et al. Sustained expression of vascular endothelial growth factor and angiopoietin-1 improves blood-spinal cord barrier integrity and functional recovery after spinal cord injury[J]. J Neurotrauma, 2010, 27(11): 2067-2076.
[11] Lu TX, Rothenberg ME. MicroRNA[J]. J Allergy Clin Immunol, 2018, 141(4): 1202-1207.
[12] Chung HJ, Chung WH, Do SH, et al. Up-regulation of microRNAs-21 and -223 in a sprague-dawley rat model of traumatic spinal cord injury[J]. Brain Sci, 2020, 10(3): 141.
[13] Jiang Y, Zhao S, Ding Y, et al. MicroRNA-21 promotes neurite outgrowth by regulating PDCD4 in a rat model of spinal cord injury[J]. Mol Med Report, 2017, 16(3): 2522-2528.
[14] Bai Y, Bai X, Wang Z, et al. MicroRNA-126 inhibits ischemia-induced retinal neovascularization via regulating angiogenic growth factors[J]. Exp Mol Pathol, 2011, 91(1):471-477.
[15] Kuhnert F, Mancuso MR, Hampton J, et al. Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126[J]. Development, 2008, 135(24): 3989-3993.
[16] van Solingen C, Seghers L, Bijkerk R, et al. Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis[J]. J Cell Mol Med, 2009, 13(8A): 1577-1585.

备注/Memo

备注/Memo:
通信作者: 石晓兵 E-mail: shixb2005@126.com
更新日期/Last Update: 2020-12-20