米诺环素对大鼠闭合性脊髓损伤的神经保护作用
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摘要
目的探讨米诺环素对大鼠急性闭合性脊髓损伤后继发性损伤的保护作用。方法 24只Sprague-Dawley雄性大鼠随机分为盐水组(n=8)、氯化镁组(n=8)和米诺环素组(n=8)。球囊压迫大鼠脊髓背侧,制备闭合性脊髓损伤模型,动物磁共振选取制模成功大鼠。各组于术后1～7 d静脉注射相应药物。术后2～31 d行BBB评分。术后31 d行运动诱发电位和感觉诱发电位检测,取脊髓损伤段行Luxol Fast Blue染色观察继发性损伤面积。结果动物磁共振显示T_(10)脊髓T_2低信号。术后17～31 d,米诺环素组BBB评分高于盐水组(P <0.05)。米诺环素组运动诱发电位振幅高于盐水组(P <0.05),继发性损伤面积小于盐水组(P <0.05)。结论米诺环素在脊髓急性损伤后,对继发性损伤有保护作用。
Objective To investigate the neuroprotective effect of minocycline on the secondary injury after acute closed spinal cord injury in rats.Methods A total of 24 Sprague-Dawley male rats were randomly divided into saline group(n = 8), magnesium chloride group(n = 8) and minocycline group(n = 8). The closed spinal cord injury model was prepared with balloon compression in the dorsal spinal cord of rat, which was evaluated with magnetic resonance imaging. All rats were successively administered their own drugs for seven days after injury, respectively. They were assessed with BBB score two to 31 days after operation. Their motor-evoked potential and sensory-evoked potential were detected 31 days after operation, and then Luxol Fast Blue was used to observe the area of secondary injury.Results Animal magnetic resonance imaging showed hypointense in T_2 images in T_(10) spinal cord. BBB score was more in the minocycline group than in the saline group since 17 days after operation(P < 0.05). The amplitude of mo‐tor-evoked potential was higher in the minocycline group than in the saline group(P < 0.05), while the area of secondary injury was less(P < 0.05).Conclusion Minocycline may protect the nerves from secondary injury after acute spinal cord injury.
Objective To investigate the neuroprotective effect of minocycline on the secondary injury after acute closed spinal cord injury in rats.Methods A total of 24 Sprague-Dawley male rats were randomly divided into saline group(n = 8), magnesium chloride group(n = 8) and minocycline group(n = 8). The closed spinal cord injury model was prepared with balloon compression in the dorsal spinal cord of rat, which was evaluated with magnetic resonance imaging. All rats were successively administered their own drugs for seven days after injury, respectively. They were assessed with BBB score two to 31 days after operation. Their motor-evoked potential and sensory-evoked potential were detected 31 days after operation, and then Luxol Fast Blue was used to observe the area of secondary injury.Results Animal magnetic resonance imaging showed hypointense in T_2 images in T_(10) spinal cord. BBB score was more in the minocycline group than in the saline group since 17 days after operation(P < 0.05). The amplitude of mo‐tor-evoked potential was higher in the minocycline group than in the saline group(P < 0.05), while the area of secondary injury was less(P < 0.05).Conclusion Minocycline may protect the nerves from secondary injury after acute spinal cord injury.
引文
[1]杨俊松,郝定均,刘团江,等.急性脊髓损伤的临床治疗进展[J].中国脊柱脊髓杂志,2018,28(4):368-373.
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[4]Ahuja C S,Wilson J R,Nori S,et al.Traumatic spinal cord injury[J].Nat Rev Dis Primers,2017,3:17018.
[5]杨永栋,赵赫,俞兴,等.脊髓损伤后继发性损伤的相关信号通路[J].中国组织工程研究,2017,21(32):5227-5233.
[6]尹彦,韩涛.三磷酸腺苷-氯化镁对兔脊髓缺血再灌注损伤保护作用研究[J].首都医药,2014(24):140-141.
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[8]姚满林,曾耀英,黄秀艳,等.米诺环素对小鼠T淋巴细胞体外活化和增殖的影响[J].现代免疫学,2008,28(2):136-141.
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[10]Garner S E,Eady A,Bennett C,et al.Minocycline for acne vulgaris:efficacy and safety[J].Cochrane Database Syst Rev2012,15(8):CD002086.
[11]Smith K,Leyden J J.Safety of doxycycline and minocycline:a systematic review[J].Clin Ther,2005,27(9):1329-1342.
[12]Lee S M,Yune T Y,Kim S J,et al.Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat[J].J Neurotrauma,2003,20(10):1017-1027.
[13]Basso D M,Beattie M S,Bresnahan J C.Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection[J].Exp Neurol1996,139(2):244-256.
[14]田伟,张焱,孙岚,等.脊髓损伤动物模型的建立及其评价[J].中国康复理论与实践,2010,16(3):221-223.
[15]Sharif-Alhoseini M,Khormali M,Rezaei M,et al.Animal models of spinal cord injury:a systematic review[J].Spinal Cord,2017,55(8):714-721.
[16]吴卓,汪玉良.脊髓损伤动物模型的研究进展[J].中国矫形外科杂志,2014,22(12):1086-1089.
[17]吴超,余上斌.临床相关的脊髓损伤动物模型新进展[J].基础医学与临床,2012,32(8):968-970.
[18]李一帆,陈东,张大威,等.急性大鼠脊髓损伤Allen's法模型的改良及电生理评价[J].中国实验诊断学,2010,14(8):1169-1172.
[19]顾兵,余彬,张海明,等.脊髓损伤后的诱发电位检查及其在动物模型评价中的应用[J].中国药理学通报,2015(9):1202-1206.
[20]Naderi Y,Sabetkasaei M,Parvardeh S,et al.Neuroprotective effect of minocycline on cognitive impairments induced by transient cerebral ischemia/reperfusion through its anti-inflammatory and anti-oxidant properties in male rat[J].Brain Res Bull,2017,131:207-213.
[21]Wells J E,Hurlbert R J,Fehlings M G,et al.Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice[J].Brain,2003,126(Pt 7):1628-1637.
[22]Teng Y D,Choi H,Onario R C,et al.Minocycline inhibits contusion-triggered mitochondrial cytochrome C release and mitigates functional deficits after spinal cord injury[J].Proc Natl Acad Sci U S A,2004,101(9):3071-3076.
[23]王刚,吴小涛,茅祖斌,等.米诺环素对大鼠脊髓损伤后线粒体细胞色素C的释放及神经细胞凋亡的影响[J].中国脊柱脊髓杂志,2006,16(7):523-526.
[24]Aras M,Altas M,Motor S,et al.Protective effects of minocycline on experimental spinal cord injury in rats[J].Injury2015,46(8):1471-1474.
[25]Ahmad M,Zakaria A,Almutairi K M.Effectiveness of minocycline and FK506 alone and in combination on enhanced behavioral and biochemical recovery from spinal cord injury in rats[J].Pharmacol Biochem Behav,2016,145:45-54.
[2]Witiw C D,Fehlings M G.Acute spinal cord injury[J].J Spinal Disord Tech,2015,28(6):202-210.
[3]Kwon B K,Tetzlaff W,Grauer J N,et al.Pathophysiology and pharmacologic treatment of acute spinal cord injury[J].Spine J,2004,4(4):451-464.
[4]Ahuja C S,Wilson J R,Nori S,et al.Traumatic spinal cord injury[J].Nat Rev Dis Primers,2017,3:17018.
[5]杨永栋,赵赫,俞兴,等.脊髓损伤后继发性损伤的相关信号通路[J].中国组织工程研究,2017,21(32):5227-5233.
[6]尹彦,韩涛.三磷酸腺苷-氯化镁对兔脊髓缺血再灌注损伤保护作用研究[J].首都医药,2014(24):140-141.
[7]Crowther C A,Middleton P F,Voysey M,et al.Assessing the neuroprotective benefits for babies of antenatal magnesium sulphate:an individual participant data meta-analysis[J].PLoSMed,2017,14(10):e1002398.
[8]姚满林,曾耀英,黄秀艳,等.米诺环素对小鼠T淋巴细胞体外活化和增殖的影响[J].现代免疫学,2008,28(2):136-141.
[9]Vandekerckhove B N,Quirynen M,van Steenberghe D.The use of locally delivered minocycline in the treatment of chronic periodontitis.A review of the literature[J].J Clin Periodontol1998,25(11 Pt2):964-968.
[10]Garner S E,Eady A,Bennett C,et al.Minocycline for acne vulgaris:efficacy and safety[J].Cochrane Database Syst Rev2012,15(8):CD002086.
[11]Smith K,Leyden J J.Safety of doxycycline and minocycline:a systematic review[J].Clin Ther,2005,27(9):1329-1342.
[12]Lee S M,Yune T Y,Kim S J,et al.Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat[J].J Neurotrauma,2003,20(10):1017-1027.
[13]Basso D M,Beattie M S,Bresnahan J C.Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection[J].Exp Neurol1996,139(2):244-256.
[14]田伟,张焱,孙岚,等.脊髓损伤动物模型的建立及其评价[J].中国康复理论与实践,2010,16(3):221-223.
[15]Sharif-Alhoseini M,Khormali M,Rezaei M,et al.Animal models of spinal cord injury:a systematic review[J].Spinal Cord,2017,55(8):714-721.
[16]吴卓,汪玉良.脊髓损伤动物模型的研究进展[J].中国矫形外科杂志,2014,22(12):1086-1089.
[17]吴超,余上斌.临床相关的脊髓损伤动物模型新进展[J].基础医学与临床,2012,32(8):968-970.
[18]李一帆,陈东,张大威,等.急性大鼠脊髓损伤Allen's法模型的改良及电生理评价[J].中国实验诊断学,2010,14(8):1169-1172.
[19]顾兵,余彬,张海明,等.脊髓损伤后的诱发电位检查及其在动物模型评价中的应用[J].中国药理学通报,2015(9):1202-1206.
[20]Naderi Y,Sabetkasaei M,Parvardeh S,et al.Neuroprotective effect of minocycline on cognitive impairments induced by transient cerebral ischemia/reperfusion through its anti-inflammatory and anti-oxidant properties in male rat[J].Brain Res Bull,2017,131:207-213.
[21]Wells J E,Hurlbert R J,Fehlings M G,et al.Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice[J].Brain,2003,126(Pt 7):1628-1637.
[22]Teng Y D,Choi H,Onario R C,et al.Minocycline inhibits contusion-triggered mitochondrial cytochrome C release and mitigates functional deficits after spinal cord injury[J].Proc Natl Acad Sci U S A,2004,101(9):3071-3076.
[23]王刚,吴小涛,茅祖斌,等.米诺环素对大鼠脊髓损伤后线粒体细胞色素C的释放及神经细胞凋亡的影响[J].中国脊柱脊髓杂志,2006,16(7):523-526.
[24]Aras M,Altas M,Motor S,et al.Protective effects of minocycline on experimental spinal cord injury in rats[J].Injury2015,46(8):1471-1474.
[25]Ahmad M,Zakaria A,Almutairi K M.Effectiveness of minocycline and FK506 alone and in combination on enhanced behavioral and biochemical recovery from spinal cord injury in rats[J].Pharmacol Biochem Behav,2016,145:45-54.
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