促红细胞生成素治疗大鼠急性脊髓损伤的Meta分析
|
摘要
目的探讨促红细胞生成素(EPO)对急性脊髓损伤大鼠运动功能恢复的影响。方法计算机检索Pub Med、Embase、Cochrane及中国生物医学数据库、维普信息数据库、中国知网及万方数据库,检索时限为数据库建库至2018年2月。采用Stata12.0软件进行Meta分析。结果共纳入16个随机对照研究,包含303只大鼠,其中EPO组152只,对照组151只。Meta分析结果表明,EPO治疗后1、2、3、4、8周,大鼠BBB评分明显高于对照组(P<0.05),6周时差异无统计学意义(P>0.05)。结论 EPO能促进脊髓损伤大鼠的运动功能恢复。
Objective To explore the effects of erythropoietin(EPO) on the motor function in rats with acute spinal cord injury (a SCI).Methods The databases including Pub Med, Embase, Cochranel Library, CBMdisc, VIP and Wang Fang were searched for the original articles about the study of the effects of EPO on the motor function in rats with a SCI. The quality of the articles was appraised according to the standard and data were extracted independently by 2 investigators. The methodology of involved trials was strictly assessed. Stata 12.0 software was used for data analysis.Results Sixteen articles of the randomized controlled trials involving 303 rats, of whom, 152 were in EPO group and 151 in the control group, were collected. The results of mta-analysis showed that the Bass Beattie Bresnahan(BBB) scale scores were significantly higher in EPO group 1, 2, 3, 4 and 8 weeks after a SCI than those in the control group[WMD=2.577, 3.304, 4.796, 4.121, 3.537; 95%CI:(1.288, 3.865),(1.652, 4.957),(2.022, 7.571),(2.623, 5.618),(1.308, 5.765)] while there was no significant difference in BBB scale scores between both the groups 6 weeks after a SCI [WMD=1.981; 95%CI:(-0.370,4.332)].Conclusions EPO can promote the recovery of motor function in rats with a SCI, but the effectiveness required being confirmed by the randomized controlled trials of larger sample.
Objective To explore the effects of erythropoietin(EPO) on the motor function in rats with acute spinal cord injury (a SCI).Methods The databases including Pub Med, Embase, Cochranel Library, CBMdisc, VIP and Wang Fang were searched for the original articles about the study of the effects of EPO on the motor function in rats with a SCI. The quality of the articles was appraised according to the standard and data were extracted independently by 2 investigators. The methodology of involved trials was strictly assessed. Stata 12.0 software was used for data analysis.Results Sixteen articles of the randomized controlled trials involving 303 rats, of whom, 152 were in EPO group and 151 in the control group, were collected. The results of mta-analysis showed that the Bass Beattie Bresnahan(BBB) scale scores were significantly higher in EPO group 1, 2, 3, 4 and 8 weeks after a SCI than those in the control group[WMD=2.577, 3.304, 4.796, 4.121, 3.537; 95%CI:(1.288, 3.865),(1.652, 4.957),(2.022, 7.571),(2.623, 5.618),(1.308, 5.765)] while there was no significant difference in BBB scale scores between both the groups 6 weeks after a SCI [WMD=1.981; 95%CI:(-0.370,4.332)].Conclusions EPO can promote the recovery of motor function in rats with a SCI, but the effectiveness required being confirmed by the randomized controlled trials of larger sample.
引文
[1]Sekhon LH,Fehings MG.Epidemiology,demographics,and pathophysiology of acute spinal cord injury[J].Spine,2001,26(24):2-12.
[2]Grant RA,Quon JL,Abbed KM.Management of acute traumatic spinal cord injury[J].Curr Treat Options Neurol,2015,17(2):334.
[3]Zhang Y,Wang L,Dey S,et al.Erythropoietin action in stress response,issue maintenance and metabolism[J].Int J Mol Sci,2014,15(6):10296-10333.
[4]王岩松,姚猛,刘斌,等.脊髓损伤后促红细胞生成素对bcl-2的影响[J].中华显微外科杂志,2006,29(2):106-109.
[5]赵晔,丁文元,张为,等.促红细胞生成素对大鼠急性脊髓损伤后后肢功能及NF-κB表达的影响[J].中国康复医学杂志,2007,22(10):904-907.
[6]孙剑瑞,殷德涛,周金桥.促红细胞生成素和羊膜间充质干细胞协同治疗促进脊髓损伤再生[J].中华实验外科杂志,2011,28(7):1087-1089.
[7]占乐云,方海滨,吕恩.促红细胞生成素和甲基泼尼松龙对大鼠急性脊髓损伤的疗效比较[J].重庆医学,2012,41(26):2746-2748.
[8]杨国宏,张春军,赵富生,等.自体骨髓基质干细胞移植联合EPO治疗脊髓损伤的研究[J].中国医学创新,2014,11(32):1-3.
[9]谢中,羊明智,胡文凯,等.EPO联合BMSCs治疗对大鼠脊髓损伤修复的影响[J].中南医学科学杂志,2015,43(3):262-265.
[10]曾智谋,范忠诚,张寿,等.骨髓间充质干细胞联合促红细胞生成素治疗大鼠脊髓损伤[J].中华实验外科杂志,2015,32(4):854-857.
[11]王康康,张辉,方晓,等.EPO治疗对大鼠脊髓损伤后脊髓运动功能恢复的实验研究[J].安徽医科大学学报,2016,51(12):1776-1780.
[12]郑竑,张韬,林振恩,等.骨髓间充质干细胞靶向移植和促红细胞生成素联合治疗脊髓损伤[J].中华实验外科杂志,2016,33(11):2490-2492.
[13]余化龙,何宁,刘志刚,等.骨髓间充质干细胞联合EPO对急性脊髓损伤大鼠神经功能的影响及机制探讨[J].山东医药,2016,56(18):37-39.
[14]Vitellaro-Zuccarello,Mazzetti S,Madaschi L,et al.Erythropoietin-mediated preservation of the white matter in rat spinal cord injury[J].Neuroscience,2007,144:865-877.
[15]Mann C,Lee JH,Liu J,et al.Delayed treatment of spinal cord injury with erythropoietin or darbepoetin-a lack of neuroprotective efficacy in a contusion model of cord injury[J].Exp Neurol,2008,211(1):34-40.
[16]Fumagalli F,Madaschi L,Brenna P,et al.Single exposure to erythropoietin modulates nerve growth factor expression in the spinal cord following traumatic injury:comparison with methylprednisolone[J].Eur J Pharmacol,2008,578(10):19-27.
[17]Ning B,Zhang A,Song H,et al.Recombinant human erythropoietin prevents motor neuron apoptosis in a rat model of cervical sub-acute spinal cord compression[J].Neurosci Lett,2011,490(1):57-62.
[18]Zhao Y,Zuo Y,Wang XL,et al.Effect of neural stem cell transplantation combined with erythropoietin injection on axon regeneration in adult rats with transected spinal cord injury[J].Genet Mol Res,2015,14(4):17799-17808.
[19]Wu MF,Zhang SQ,Gu R,et al.Transplantation of erythropoietin gene-modified neural stem cells improves the repair of injured spinal cord[J].Neural Regen Res,2015,10(9):1483-1490.
[20]Basso DM,Beattie MS,Bresnahan JC.A sensitive and reliable locomotor rating scale for open field testing in rats[J].J Neurotrauma,1995,12(1):1-21.
[21]Thanka T,Nangaku M.Recent advances and clinical application of erythropoietin and erythropoiesis-stimulating agents[J].Exp Cell Ress,2012,318(9):1068-1073.
[22]Zhang J,Li Y,Gui Y,et al.Erythropoietin treatment improves neurological functional recovery in EAE mice[J].Brain Res,2005,1034(1-2):34-39.
[23]Agnello D,Bigini P,Villa P,et al.Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis[J].brain Res,2002,952(1):128-134.
[24]朱丽华,施燕,王诗雨,等.人重组促红细胞生成素对早产儿脑室周围白质损伤模型鼠脑血管生成的影响[J].中华实用儿科临床杂志,2015,30(9):698-701.
[25]Iwai W,Stetler RA,Xing J,et al.Enhanced oligodendrogenesis and recovery of neurological function by erythropoietin after neonatal hypoxic/ischemic brain injury[J].Stroke,2010,41(5):1032-1037.
[26]Gorio A,Gokmen N,Erbayraktar S,et al.Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma[J].Proc Natl Acad Sci U S A,2002,99(14):9450-9455.
[27]Alibai EA,Baqhban F,Farrokhi MR,et al.Effects of human erythropoietin on functional outcome of patients with traumatic cervical cord injury:a pilot randomized clinical trial[J].Bull Emerg Trauma,2015,3(3):79-85.
[28]Xiong M,Chen S,Yu H,et al.Neuroprotection of erythropoietin and methylprednisolone against spinal cord ischemiareperfusion injury[J].J Huazhong Univ Sci Technolog Med Sci,2011,31(5):652-656.
[29]Costa DD,Beqhi E,Cariqnano P,et al.Tolerability and efficacy of erythropoietin(EPO)treatment in traumatic spinal cord injury:a preliminary randomized comparative trail vs.methylprednisolone(MP)[J].Neurol Sci,2015,36(9):1567-1574.
[30]胡杨,廉凯,秦文,等.促红细胞生成素联合甲泼尼龙治疗急性脊髓损伤的临床研究[J].临床急诊杂志,2011,12(5):298-300.
[31]何玉宝,赵云华,任龙喜,等.重组人促红细胞生成素联合甲泼尼龙琥珀酸治疗急性脊髓损伤的临床效果观察[J].中国综合临床,2017,33(8):742-747.
[2]Grant RA,Quon JL,Abbed KM.Management of acute traumatic spinal cord injury[J].Curr Treat Options Neurol,2015,17(2):334.
[3]Zhang Y,Wang L,Dey S,et al.Erythropoietin action in stress response,issue maintenance and metabolism[J].Int J Mol Sci,2014,15(6):10296-10333.
[4]王岩松,姚猛,刘斌,等.脊髓损伤后促红细胞生成素对bcl-2的影响[J].中华显微外科杂志,2006,29(2):106-109.
[5]赵晔,丁文元,张为,等.促红细胞生成素对大鼠急性脊髓损伤后后肢功能及NF-κB表达的影响[J].中国康复医学杂志,2007,22(10):904-907.
[6]孙剑瑞,殷德涛,周金桥.促红细胞生成素和羊膜间充质干细胞协同治疗促进脊髓损伤再生[J].中华实验外科杂志,2011,28(7):1087-1089.
[7]占乐云,方海滨,吕恩.促红细胞生成素和甲基泼尼松龙对大鼠急性脊髓损伤的疗效比较[J].重庆医学,2012,41(26):2746-2748.
[8]杨国宏,张春军,赵富生,等.自体骨髓基质干细胞移植联合EPO治疗脊髓损伤的研究[J].中国医学创新,2014,11(32):1-3.
[9]谢中,羊明智,胡文凯,等.EPO联合BMSCs治疗对大鼠脊髓损伤修复的影响[J].中南医学科学杂志,2015,43(3):262-265.
[10]曾智谋,范忠诚,张寿,等.骨髓间充质干细胞联合促红细胞生成素治疗大鼠脊髓损伤[J].中华实验外科杂志,2015,32(4):854-857.
[11]王康康,张辉,方晓,等.EPO治疗对大鼠脊髓损伤后脊髓运动功能恢复的实验研究[J].安徽医科大学学报,2016,51(12):1776-1780.
[12]郑竑,张韬,林振恩,等.骨髓间充质干细胞靶向移植和促红细胞生成素联合治疗脊髓损伤[J].中华实验外科杂志,2016,33(11):2490-2492.
[13]余化龙,何宁,刘志刚,等.骨髓间充质干细胞联合EPO对急性脊髓损伤大鼠神经功能的影响及机制探讨[J].山东医药,2016,56(18):37-39.
[14]Vitellaro-Zuccarello,Mazzetti S,Madaschi L,et al.Erythropoietin-mediated preservation of the white matter in rat spinal cord injury[J].Neuroscience,2007,144:865-877.
[15]Mann C,Lee JH,Liu J,et al.Delayed treatment of spinal cord injury with erythropoietin or darbepoetin-a lack of neuroprotective efficacy in a contusion model of cord injury[J].Exp Neurol,2008,211(1):34-40.
[16]Fumagalli F,Madaschi L,Brenna P,et al.Single exposure to erythropoietin modulates nerve growth factor expression in the spinal cord following traumatic injury:comparison with methylprednisolone[J].Eur J Pharmacol,2008,578(10):19-27.
[17]Ning B,Zhang A,Song H,et al.Recombinant human erythropoietin prevents motor neuron apoptosis in a rat model of cervical sub-acute spinal cord compression[J].Neurosci Lett,2011,490(1):57-62.
[18]Zhao Y,Zuo Y,Wang XL,et al.Effect of neural stem cell transplantation combined with erythropoietin injection on axon regeneration in adult rats with transected spinal cord injury[J].Genet Mol Res,2015,14(4):17799-17808.
[19]Wu MF,Zhang SQ,Gu R,et al.Transplantation of erythropoietin gene-modified neural stem cells improves the repair of injured spinal cord[J].Neural Regen Res,2015,10(9):1483-1490.
[20]Basso DM,Beattie MS,Bresnahan JC.A sensitive and reliable locomotor rating scale for open field testing in rats[J].J Neurotrauma,1995,12(1):1-21.
[21]Thanka T,Nangaku M.Recent advances and clinical application of erythropoietin and erythropoiesis-stimulating agents[J].Exp Cell Ress,2012,318(9):1068-1073.
[22]Zhang J,Li Y,Gui Y,et al.Erythropoietin treatment improves neurological functional recovery in EAE mice[J].Brain Res,2005,1034(1-2):34-39.
[23]Agnello D,Bigini P,Villa P,et al.Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis[J].brain Res,2002,952(1):128-134.
[24]朱丽华,施燕,王诗雨,等.人重组促红细胞生成素对早产儿脑室周围白质损伤模型鼠脑血管生成的影响[J].中华实用儿科临床杂志,2015,30(9):698-701.
[25]Iwai W,Stetler RA,Xing J,et al.Enhanced oligodendrogenesis and recovery of neurological function by erythropoietin after neonatal hypoxic/ischemic brain injury[J].Stroke,2010,41(5):1032-1037.
[26]Gorio A,Gokmen N,Erbayraktar S,et al.Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma[J].Proc Natl Acad Sci U S A,2002,99(14):9450-9455.
[27]Alibai EA,Baqhban F,Farrokhi MR,et al.Effects of human erythropoietin on functional outcome of patients with traumatic cervical cord injury:a pilot randomized clinical trial[J].Bull Emerg Trauma,2015,3(3):79-85.
[28]Xiong M,Chen S,Yu H,et al.Neuroprotection of erythropoietin and methylprednisolone against spinal cord ischemiareperfusion injury[J].J Huazhong Univ Sci Technolog Med Sci,2011,31(5):652-656.
[29]Costa DD,Beqhi E,Cariqnano P,et al.Tolerability and efficacy of erythropoietin(EPO)treatment in traumatic spinal cord injury:a preliminary randomized comparative trail vs.methylprednisolone(MP)[J].Neurol Sci,2015,36(9):1567-1574.
[30]胡杨,廉凯,秦文,等.促红细胞生成素联合甲泼尼龙治疗急性脊髓损伤的临床研究[J].临床急诊杂志,2011,12(5):298-300.
[31]何玉宝,赵云华,任龙喜,等.重组人促红细胞生成素联合甲泼尼龙琥珀酸治疗急性脊髓损伤的临床效果观察[J].中国综合临床,2017,33(8):742-747.