甲基强的松龙上调缺血再灌注损伤脊髓热休克蛋白27表达的剂量研究
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摘要
背景与目的
脊髓是中枢神经的一部分,不仅为支配肢体运动、感觉、内脏活动的低级中枢,而且是联系大脑和外周神经系统的关键结构,上、下行神经传导束密集。局部的损伤也会有严重的后果,如永久性的瘫痪、感觉功能丧失、大小便功能障碍以及植物神经功能紊乱等症状。因此脊髓损伤是致死率和致残率非常高的疾病,给患者及其家庭带来极大地经济和心理负担。不过脊髓损伤后神经功能的保护和恢复对于医学界仍然是一大世界性难题,在过去几十年国内外广大科研工作者孜孜不倦努力,虽然没有彻底攻克它,但也取得了一些进展。
已有研究表明神经细胞在受到应激性刺激后会马上产生热休克蛋白(heat shock proteins, HSPs),其中热休克蛋白27(HSP27)能够通过各种机制对神经细胞起保护作用。有一些因素能促使神经细胞产生HSP27,但这种方法目前还无法应用于临床。如果通过药物诱导HSP27在脊髓内大量地表达,对临床脊髓损伤治疗则具有重要的现实意义。甲基强的松龙(MethylprednisoloneMP)是美国FDA批准的唯一一个用于治疗脊髓损伤的药物。研究表明它能够诱导HSP27表达量的上调来发挥对脊髓神经细胞的保护作用。经过美国3次全国急性脊髓损伤研究,其标准治疗方案已经在世界各地广泛应用于急性脊髓损伤。但是临床上缺血再灌注脊髓损伤(spinal cord ischemic reperfusion injury SCⅡ)非常多见,如严重的脊髓性颈椎病、胸椎管狭窄等手术减压术后都会导致脊髓缺血再灌注损伤。如果能够应用MP有效减轻缺血再灌注脊髓损伤,对于脊柱疾病的治疗将是个非常大的进步。不过对于MP治疗缺血再灌注脊髓损伤的用法尚没有统一的标准,临床和科研工作者也都是在探索性应用。已经有人研究发现应用MP治疗缺血再灌注的比较合适时间点是损伤前30分钟,但是应用MP的比较好的剂量目前尚未见相关报道。
本课题通过制作缺血再灌注脊髓损伤动物模型,在损伤前30分钟静脉给于不同剂量的甲基强的松龙,免疫组织化学法检测脊髓组织细胞内HSP27的表达,来探讨甲基强的松龙通过诱导脊髓组织细胞内HSP27的表达而起到神经保护作用的比较好的剂量。
材料与方法
1.动物模型制作和分组健康普通级成年大鼠(郑州大学实验动物中心提供)100只,雌雄不分,质量200±20g。随机分成5组：A组(正常组)20只；B组(缺血再灌注模型组)20只大鼠,三个治疗组C组、D组及E组各20只大鼠。采用夹闭左右肾动脉间腹主动脉30分钟再灌注3个小时的方法制作SCⅡ模型；C组、D组及E组在脊髓缺血前30分钟分别给予MP剂量为10mg/kg、20mg/kg、30mg/kg,用生理盐水稀释至0.5ml从大鼠尾部静脉注射,B组给于相同剂量的生理盐水。
2.标本取材实验动物麻醉后用4%多聚甲醛全身灌注,咬除T11、T12、L1棘突和椎板后从圆锥开始向上取脊髓约1cm,常规甲醛固定,脱水,石蜡包埋,切片,HE染色和免疫组织化学染色。
3.免疫组织化学染色和图像分析切片免疫组织化学染色后采用图像分析系统测量阳性染色物质吸光度,每张片随机选取6个不同视野,400高倍镜下用计算机计算出平均吸光度值A,A反应染色强度,代表相对含量。
4.统计学处理用SPSS13.0统计分析软件处理实验数据,所有数据采用均数加减标准差(x±s)表示,按α=0.05检验水准,五个样本均数组间采用单因素方差分析(ANOVA)进行数据处理,组间两两比较采用LSD法。
结果
1.大鼠脊髓缺血再灌注损伤后,损伤处有明显水肿、变性、坏死等病理变化。
2.正常组脊髓内HSP27的表达量呈弱阳性,缺血再灌注组脊髓神经细胞内HSP27表达量明显增加。
3.缺血再灌注组损伤前使用MP,脊髓的继发性损伤减轻,HSP27的表达量明显增强,显示为强阳性。
4.HSP27的表达水平上,五组之间总体上差异有统计学意义(P<0.05),B组与A组差异性有统计学意义(P<0.05),C组与B组差异性无统计学意义(P>0.05),D组和C组差异性有统计学意义(P<0.05),E组和D组差异性有统计学意义(P<0.05)。
结论
1.在缺血再灌注损伤前预防性使用MP可明显改善损伤脊髓的病理形态,表明脊髓缺血再灌注损伤前早期使用MP对损伤脊髓有一定的保护作用。
2.正常脊髓神经细胞内HSP27的表达呈弱阳性,大鼠脊髓缺血再灌注损伤后脊髓神经细胞内HSP27的表达明显上调,而在脊髓损伤前使用MP可使大鼠脊髓神经细胞HSP27的表达显著提高。
3.脊髓缺血再灌注损伤前预防性应用不同剂量MP使脊髓神经细胞内HSP27表达量上调程度不同,30mg/kgMP治疗组HSP27表达上调最明显。
Background and Objective
As a part of the central nervous system, the spinal cord is not only a junior centrum controling body movement, feeling, internal activity,but also but also is a key structure communicating the brain with peripheral nervous system, where there are dense fasciculuses. So even there is a focal injury to the spinal cord, it can induce a severe result such as permanent paralysis, feeling function losing, defecation function disturbance and vegetative nerve functional disturbance. So the morbidity of death and deformity in spinal cord injury is very high, which bring great economy and psychological burden. But protection and restoration of nerve function after spinal cord injury for medicine is still a big problem in the world. Although it is not totally conquered, some progress has been also made through tireless efforts of scientists in the past few decades. Studies have shown that nerve cells will quickly generate heat shock protein after stimulation and HSP27 of nerve cells can play protective effect through various mechanisms. Many factors can cause nerve cells to produce HSP27, but these methods are still unable to be used in clinical applications.It will have important practical significance in clinical treatment of spinal cord injury if HSP27 is induced by drugs in the spinal cord of expression.
Methylprednisolone is only medicine used in clinic approved by FDA. Research shows that it can raise HSP27 expression to protect spinal nerve cell. After U.S. three national acute spinal cord injury study, the standard therapy in the world has been widely applied in acute spinal cord injury.But there is much SCII(Spinal Cord ischemia-reperfusion Injury) phenomenon in clinic, spinal cord ischemia-reperfusion injury can appear after decompression surgery such as severe spinal cord of cervical spondylosis, thoracic spinal stenosis. If the application of MP can effectively reduce ischemia-reperfusion for spinal cord injury, the treatment of spinal column diseases is a very big progress.But there is not a unified standard for MP usage in treatment of spinal cord ischemic reperfusion injury, clinical and scientific researchers are also exploring the application. Some people has found that the best time of using MP in treatment of SCⅡ, but the best dose has not been reported.
This study is to discover the better MP dose of protecting spinal cord by inducing the expression of HSP27 through such methods as making animal models of spinal cord ischemia-reperfusion injury, using different doses of Methylprednisolone within 30 minutes before SCⅡ,detecting the expression of the HSP27 of rats'spinal cord by immunohistochemstry
Methods
100 ordinary rats were randomly divided into five groups (n=20):Group A、B、C、D and E, normal group、SCⅡgroup、MP treatment groups (three different doses ).we obstructed the abdominal aorta between the left and the right renal artery for 30min and let it receive reperfusion after 3h to make the SCⅡmodel.At 30min prior to injury, the rats in C, D and E group received 10mg/kg、20mg/kg、30mg/kgMP respectively.And the rats in group B received the same dose of normal saline as control before injury. The spinal cord specimen from group A 3h after surgery and from other groups 3h after injury were taken out and cut ,then the pathological changes of spinal cord cells with HE staining and the expression of Hsp27 in spinal cord cells with immunohistochemical staining were observed respectively. The data were analysed with SPSS 13.0 soft ware.
Results
1. There were significantly edema, degeneration, necrosis and so on in spinal cord after SCⅡin rats
2. The expression of HSP27 showed weak positive in the normal group and obviouly increased in SCⅡgroup.
3. The secondary injury of spinal cord was significantly improved in MP group. The expression of HSP27 significantly increased and showed strong positive.
4. In the expression of HSP27,there was a significant difference among each group in total (P<0.05); There was significant statistical difference between group B and group A(P<0.05). NO significant statistical difference was found in the expression between group B and group C (P>0.05). There was significant statistical difference between group D and group C (P<0.05) and also statistical significance was found between group E and group D (P<0.05).
Conclucions
1. The pathological morphology of spinal cord can be obviously improved when preventive using MP before SCⅡ, and it appears that early using MP before SCⅡhas certain protective effect to some protective effect.
2. HSP27 expression is weak positive in normal spinal nerve cells and is up-regulated after SCⅡ,but its expression will be up-regulated significantly when using MP at 30min prior to injury.
3. HSP27 expression is up-regulated at different levels when using different doses MP prior to injury, and 30mg/kg MP is the best dose.
脊髓是中枢神经的一部分,不仅为支配肢体运动、感觉、内脏活动的低级中枢,而且是联系大脑和外周神经系统的关键结构,上、下行神经传导束密集。局部的损伤也会有严重的后果,如永久性的瘫痪、感觉功能丧失、大小便功能障碍以及植物神经功能紊乱等症状。因此脊髓损伤是致死率和致残率非常高的疾病,给患者及其家庭带来极大地经济和心理负担。不过脊髓损伤后神经功能的保护和恢复对于医学界仍然是一大世界性难题,在过去几十年国内外广大科研工作者孜孜不倦努力,虽然没有彻底攻克它,但也取得了一些进展。
已有研究表明神经细胞在受到应激性刺激后会马上产生热休克蛋白(heat shock proteins, HSPs),其中热休克蛋白27(HSP27)能够通过各种机制对神经细胞起保护作用。有一些因素能促使神经细胞产生HSP27,但这种方法目前还无法应用于临床。如果通过药物诱导HSP27在脊髓内大量地表达,对临床脊髓损伤治疗则具有重要的现实意义。甲基强的松龙(MethylprednisoloneMP)是美国FDA批准的唯一一个用于治疗脊髓损伤的药物。研究表明它能够诱导HSP27表达量的上调来发挥对脊髓神经细胞的保护作用。经过美国3次全国急性脊髓损伤研究,其标准治疗方案已经在世界各地广泛应用于急性脊髓损伤。但是临床上缺血再灌注脊髓损伤(spinal cord ischemic reperfusion injury SCⅡ)非常多见,如严重的脊髓性颈椎病、胸椎管狭窄等手术减压术后都会导致脊髓缺血再灌注损伤。如果能够应用MP有效减轻缺血再灌注脊髓损伤,对于脊柱疾病的治疗将是个非常大的进步。不过对于MP治疗缺血再灌注脊髓损伤的用法尚没有统一的标准,临床和科研工作者也都是在探索性应用。已经有人研究发现应用MP治疗缺血再灌注的比较合适时间点是损伤前30分钟,但是应用MP的比较好的剂量目前尚未见相关报道。
本课题通过制作缺血再灌注脊髓损伤动物模型,在损伤前30分钟静脉给于不同剂量的甲基强的松龙,免疫组织化学法检测脊髓组织细胞内HSP27的表达,来探讨甲基强的松龙通过诱导脊髓组织细胞内HSP27的表达而起到神经保护作用的比较好的剂量。
材料与方法
1.动物模型制作和分组健康普通级成年大鼠(郑州大学实验动物中心提供)100只,雌雄不分,质量200±20g。随机分成5组：A组(正常组)20只；B组(缺血再灌注模型组)20只大鼠,三个治疗组C组、D组及E组各20只大鼠。采用夹闭左右肾动脉间腹主动脉30分钟再灌注3个小时的方法制作SCⅡ模型；C组、D组及E组在脊髓缺血前30分钟分别给予MP剂量为10mg/kg、20mg/kg、30mg/kg,用生理盐水稀释至0.5ml从大鼠尾部静脉注射,B组给于相同剂量的生理盐水。
2.标本取材实验动物麻醉后用4%多聚甲醛全身灌注,咬除T11、T12、L1棘突和椎板后从圆锥开始向上取脊髓约1cm,常规甲醛固定,脱水,石蜡包埋,切片,HE染色和免疫组织化学染色。
3.免疫组织化学染色和图像分析切片免疫组织化学染色后采用图像分析系统测量阳性染色物质吸光度,每张片随机选取6个不同视野,400高倍镜下用计算机计算出平均吸光度值A,A反应染色强度,代表相对含量。
4.统计学处理用SPSS13.0统计分析软件处理实验数据,所有数据采用均数加减标准差(x±s)表示,按α=0.05检验水准,五个样本均数组间采用单因素方差分析(ANOVA)进行数据处理,组间两两比较采用LSD法。
结果
1.大鼠脊髓缺血再灌注损伤后,损伤处有明显水肿、变性、坏死等病理变化。
2.正常组脊髓内HSP27的表达量呈弱阳性,缺血再灌注组脊髓神经细胞内HSP27表达量明显增加。
3.缺血再灌注组损伤前使用MP,脊髓的继发性损伤减轻,HSP27的表达量明显增强,显示为强阳性。
4.HSP27的表达水平上,五组之间总体上差异有统计学意义(P<0.05),B组与A组差异性有统计学意义(P<0.05),C组与B组差异性无统计学意义(P>0.05),D组和C组差异性有统计学意义(P<0.05),E组和D组差异性有统计学意义(P<0.05)。
结论
1.在缺血再灌注损伤前预防性使用MP可明显改善损伤脊髓的病理形态,表明脊髓缺血再灌注损伤前早期使用MP对损伤脊髓有一定的保护作用。
2.正常脊髓神经细胞内HSP27的表达呈弱阳性,大鼠脊髓缺血再灌注损伤后脊髓神经细胞内HSP27的表达明显上调,而在脊髓损伤前使用MP可使大鼠脊髓神经细胞HSP27的表达显著提高。
3.脊髓缺血再灌注损伤前预防性应用不同剂量MP使脊髓神经细胞内HSP27表达量上调程度不同,30mg/kgMP治疗组HSP27表达上调最明显。
Background and Objective
As a part of the central nervous system, the spinal cord is not only a junior centrum controling body movement, feeling, internal activity,but also but also is a key structure communicating the brain with peripheral nervous system, where there are dense fasciculuses. So even there is a focal injury to the spinal cord, it can induce a severe result such as permanent paralysis, feeling function losing, defecation function disturbance and vegetative nerve functional disturbance. So the morbidity of death and deformity in spinal cord injury is very high, which bring great economy and psychological burden. But protection and restoration of nerve function after spinal cord injury for medicine is still a big problem in the world. Although it is not totally conquered, some progress has been also made through tireless efforts of scientists in the past few decades. Studies have shown that nerve cells will quickly generate heat shock protein after stimulation and HSP27 of nerve cells can play protective effect through various mechanisms. Many factors can cause nerve cells to produce HSP27, but these methods are still unable to be used in clinical applications.It will have important practical significance in clinical treatment of spinal cord injury if HSP27 is induced by drugs in the spinal cord of expression.
Methylprednisolone is only medicine used in clinic approved by FDA. Research shows that it can raise HSP27 expression to protect spinal nerve cell. After U.S. three national acute spinal cord injury study, the standard therapy in the world has been widely applied in acute spinal cord injury.But there is much SCII(Spinal Cord ischemia-reperfusion Injury) phenomenon in clinic, spinal cord ischemia-reperfusion injury can appear after decompression surgery such as severe spinal cord of cervical spondylosis, thoracic spinal stenosis. If the application of MP can effectively reduce ischemia-reperfusion for spinal cord injury, the treatment of spinal column diseases is a very big progress.But there is not a unified standard for MP usage in treatment of spinal cord ischemic reperfusion injury, clinical and scientific researchers are also exploring the application. Some people has found that the best time of using MP in treatment of SCⅡ, but the best dose has not been reported.
This study is to discover the better MP dose of protecting spinal cord by inducing the expression of HSP27 through such methods as making animal models of spinal cord ischemia-reperfusion injury, using different doses of Methylprednisolone within 30 minutes before SCⅡ,detecting the expression of the HSP27 of rats'spinal cord by immunohistochemstry
Methods
100 ordinary rats were randomly divided into five groups (n=20):Group A、B、C、D and E, normal group、SCⅡgroup、MP treatment groups (three different doses ).we obstructed the abdominal aorta between the left and the right renal artery for 30min and let it receive reperfusion after 3h to make the SCⅡmodel.At 30min prior to injury, the rats in C, D and E group received 10mg/kg、20mg/kg、30mg/kgMP respectively.And the rats in group B received the same dose of normal saline as control before injury. The spinal cord specimen from group A 3h after surgery and from other groups 3h after injury were taken out and cut ,then the pathological changes of spinal cord cells with HE staining and the expression of Hsp27 in spinal cord cells with immunohistochemical staining were observed respectively. The data were analysed with SPSS 13.0 soft ware.
Results
1. There were significantly edema, degeneration, necrosis and so on in spinal cord after SCⅡin rats
2. The expression of HSP27 showed weak positive in the normal group and obviouly increased in SCⅡgroup.
3. The secondary injury of spinal cord was significantly improved in MP group. The expression of HSP27 significantly increased and showed strong positive.
4. In the expression of HSP27,there was a significant difference among each group in total (P<0.05); There was significant statistical difference between group B and group A(P<0.05). NO significant statistical difference was found in the expression between group B and group C (P>0.05). There was significant statistical difference between group D and group C (P<0.05) and also statistical significance was found between group E and group D (P<0.05).
Conclucions
1. The pathological morphology of spinal cord can be obviously improved when preventive using MP before SCⅡ, and it appears that early using MP before SCⅡhas certain protective effect to some protective effect.
2. HSP27 expression is weak positive in normal spinal nerve cells and is up-regulated after SCⅡ,but its expression will be up-regulated significantly when using MP at 30min prior to injury.
3. HSP27 expression is up-regulated at different levels when using different doses MP prior to injury, and 30mg/kg MP is the best dose.
引文
[1]Braughler JM,Hall ED. Uptake and elimination of methylprednisolone fromcontused cat spinal cord following intravenous injection of the sodium succinate e ster[J].J Neurosurg,1983,58(4):538-542.
[2]姜建元,顾湘杰.有关脊髓缺血再灌注损伤的几个问题.脊柱外科杂志,2005,01,57-59
[3]Sauerland S,Nagelschmidt M,Mallmann P,et al.Risks and benefits of preoperative high dose methylprednisolone in surgical patients:a systematic review [J].Drug Saf,2000,23 (5):449--461
[4]Bracken MB, Steroids for acute spinal cord injury. Cochrane Database Syst Rev 2002(3):cd001046.
[5]Katircioglu SF, Seren M,Parlar AI,et al. Levosimendan effect on spinal cord ischemia-reperfusion injury following aortic clamping [J]. J Card Surg,2008,23(1): 44-48.
[6]Qayum 1 AK, Janusz M T, Lystir DM, et al. Animal model for investigation of spinal cord injury caused by aoutic ccross-clamp ing. J Invest surg,1997,10:47-52.
[7]伍亚民,王正国,朱佩芳,等.脊髓缺血损伤动物模型及行为的实验研究.中华创伤外科杂志,2000,16：157-159.
[8]镇万新,张铁良,黄琪裳,王炳勋.钙阻断剂与激素对实验性脊髓损伤的作用比较.中华骨科杂志,1993,13(6)：439-442.
[9]Young W. Secondary injury mechanisms in acute spinal cord injury. J Emerg Med,1993, 11 Suppl 1:13-22.
[10]Olney JW, Ariga TV.Cytotoxic effects of acidic sulpher containing amino acids on the infant mouse central nervous system. Exp.BrainRes,1971,14(1):61-66.
[11]Choi DW.Ionic dependence of glutamate neurotoxity.J Neurosci,1987,7(2):369-372.
[12]刘连生,廖维宏.脊髓损伤及其继发损伤时的兴奋性氨基酸含量变化.中华神经外科杂志,1994,10(20)：70-72.
[13]Ip WK,Wong CK, Lam CW. Tumour necrosis factor-alpha-in-duced expression of intercellular adhension molecule-1 on human eosinophilic leukaemia Eol-1 cells ismediateded by the activation of nuclear factor-kappaB pathway. Clin Exp Allergy,2003, 33:242-248
[14]Farhood A, McGurie GM, ManningAM, et a.l Intercellular adhensionmolecule 1 expression and its role in neutrophil-induced ischemia-reperfusion injury in rat liver. Leukoc Bio,l 1995,57:368-374
[15]朱庆三,尹飞,郭丽,等.脊髓缺血再灌注损伤中神经细胞凋亡的研究.吉林大学学报,2003,29：609-610
[16]Cassada DC, Tribble CG, Kaza AK, et a.l Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion. Surgery,2001,130:230-235
[17]Bracken MB, Steroids for acute spinal cord injury. Cochrane Database Syst Rev 2002(3):cd001046.
[18]Bracken MB,Holgord TR, Neurological and functional status 1 year after acute spinal cord injury:estimates of functional recovery in National Acute Spinal Cord Injury Study II from results modeled in National Acute Spinal Cord Injury Study III. J Neurosurg (Spine 3) 2002;96:2 59～66.
[19]Braughler JM,Hall ED. Uptake and elimination of methylprednisolone from contused cat spinal cord following intravenous injection of the sodium succinate ester[J].J Neurosurg, 1983,58(4):538-542.
[20]Michael Costigan, Richard J, Mannion, et al. Heat shock protein 27:evelopmental regulation and expression after peripheral nerve injury.1998,18(15):5891-5901.
[21]Martin JL, Mestril R, Hilal-Dandan R, et al. Small heat shock proteins and protection against ischemic injury in cardiac myocytes. Circulation,1997,96:4343-4348.
[22]Ritossa, F.A new puffing pattern induced and temperature shock and DNP in Drosophila[J] Experientia,1962,18:571-573.
[23]Adams C, et al. Stress protein formation:gene expression and environmental interaction with evolutionary significance. Int Rev Cytol 1982;79:305.
[24]Cotto JJ,Morimoto RJ, et al.Stress-induced activation of the heat-shock response:cell and molecular biology of heat-shock factors.Biochem Soc Symp.1999;64:105-18. Review.
[25]Gernold M, Knauf U, Gaestel M,Stahl J, Kloetzel PM,1993. Development and tissue-specific distribution of mouse small heat shock protein HSP25. Dev Genet 14:103-111.
[26]Wilkinson JM, Pollard I,1993. Immunohistochemical localization of the 25kDa heat shock protein in unstressed rats:Possible functional implications. Anat Rec 237:453-457.
[27]Spector NL, et al.28-kDa mammalian heat shock protein, a novel substrate of a growth regulatory protease involved in differentiation of human leukemia cells. J Biol Chem,1995; 273:1003-1006.
[28]Ciocca DR, Oesterreich S, Chamness GC, Mcguire WL, Fuqua SAW,1993. Biological and clinical implications of heat shock protein 27000(HSP27):a review. J Natl Cancer Inst85:1558-1570.
[29]Lutsch G, Vetter R, Offhauss U, et al. Abundance and location of the small heat shock proteins HSP25 and alphaB-crystallin in rat and human heart. Circulation,1997,96:3466-3476.
[30]Klemenz R, Andres AC, Frohli E, Schafer R, Aoyama A,1993. Expression of the murine small heat shock proteins HSP25 and a b crystallin in the absence of stress .J Cell Biol 120:639-645.
[31]Csermely P, Schnaider T, Soti C, et al. The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. Pharmacol Ther,1998, 79:129-168.
[32]Rutherford SL, et al. Protein folding and the regulation of signaling pathways. Cell,1994;79:1129-1132.
[33]Lstchman DS. Protection of neuronal and cardiac cells by H SP27.Prog Mol Subcell Biol,2002,28 (2):253-265.
[34]刘弈蓉等热休克蛋白27在大鼠脊髓前角中的表达明中国煤炭工业医学杂志.2004,1(7)179-80.
[35]姜苏蓉 刘莉 程蕴琳 热休克蛋白27抗细胞凋亡的分子机制。中华老年医学杂志2004年2月第23卷第2期138-140.
[36]BuchnerJ. HSP90&Co.-a holding for folding[J].Trends BiochemSci,1999,24 (4):136-141.
[37]EllisR J. The molecular chaperone concept[J].Semin Cell Biol,1990,1(1):1-9.
[38]Chamberlain LH, Burgoyne RD. Activation of the ATPase activity of heat-shock proteins Hsc70/HSP70 by cysteine-string protein[J].Biochem J,1997,32 2(R3):853-858.
[39]Koide T, Asada S, Nagata K.Substrate recognition of collagen-specificmolecular chaperone HSP47. Structural requirements and binding regulation [J].J Biol Chem,1999, 274(49):34523-34526.
[40]AsadaS, Koide T, Yasui H, Nagata K. Effect of HSP47 on proly14-hydroxylation of collagen model peptides [J].Cell Struct Funct,1999,24(4):187-196.
[41]Lambert H, Charette SJ, Bernier AF, et al. HSP27 multimerization mediated by phosphorylation-sensitive intermolecular interactions at the amino terminus [J].J Biol Chem,1999,274(14):9378-9385.
[42]Preville X, Salvemini F, Giraud S. Mammalian small stress proteins protect against oxidative stress through their ability to increase glucose-6-phosphate dehydrogenase activity and by maintaining optimal cellular detoxifying machinery[J].Exp Cell Res,19 99,247(1):61-78.
[43]Arrigo AP. Small stress proteins:chaperones that acts as regulators of intracellular redox state and programmed cell death. Biol Chem,1998,379(1):19-26.
[44]Mehlen P, Kretz-Remy C, Preville X, et al. Human HSP27, Drosophila HSP27, or human a b-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFa-induced cell death. EMBO J,1996,15:2695-2706.
[45]SakuraiM,Hayashi T,Abe K,et al.Delayed selective motor neuron death and fas antigen induction after spinal cord ischemia in rabbits [J]. Brain Res,1998,79 7:23 -28.
[46]Leskovar A, Moriarty L J, Turek JJ,et al. The macrophage in acute neural injury: changes in cell numbers over time and levels of cytokine production in mammalian central and peripheral nervous systems[J]. J Exp Biol,2000,203:1783-1795.
[47]Paul,C ,Manero,F, et al.HSP27 as a negative regulator of cytochrome C release [J].Molecular and Cellular Biology2002,22:816-834.
[48]Garrido,C ,Bruey, J- M, et al.HSP27 inhibits cytochrome c-dependent activation of procaspase-9 FASEB Journal 1999,13:2061-2070
[49]Bracy,J- M,Ducasse,C ,Bonniaud,P,et al. HSP27 negatively regulates cell death by interacting with cytochrome [J].Nature Cell Biology 2000,2:645-652.
[50]Marcus J.D Wagstaff; Yolanda Collago-Moraes; Benjamin S.Aspey, et al, Focal cerebral ischaemia increases the levels of several classes of heat shock proteins and their corresponding mRNAs Molecular Brain Research 42(1996):236-244.
[51]Hiroyuki Kato; Kyuya Kogure; Xiao-Hong Liu; et al. Immunohistochemical localization of the low molecular weight stress protein HSP27 following focal cerebral ischemia in the rat Brain research 679(1995):1-7.
[52]R. William Currie, Julie A. Ellison, Ray F. White, Giora Z. Feuerstein, b b,Xinkang Wang, Frank C. Barone Benign focal ischemic preconditioning induces neuronal HSP70 and prolonged astrogliosis with expression of HSP27. Brain Research 863(2000)169-181.
[53][53] Cuesta R, Laroia G, Schneider RJ. Chaperone hsp27 inhibits translation during heat shock by binding eIF4G and facilitating dissociation of cap-initiation complexes Genes Dev,2000,14(12):1460-1470.
[54]Xu J Kim GM Ahmed SH. Glucocorticoid receptor-mediated suppression of acticitor protein -1 activation and matrix metalloproteinase expression after spinal cord injury [J].J Neurosci 2001 21 1 92-97.
[55]Veerkamp JH, Zimmerman AW.Fatty acid-binding proteins of nervous tissue[J].J Mol neurosci,2001,16(2-3):133-157
[56]Braughler JM,Hall ED. Uptake and elimination of methylprednisolone from c ontused cat spinal cord following intravenous injection of the sodium succinate e ster[J].J Neurosurg, 1983,58(4):538-542.
[57]YoungWlMethylp rednis ol one and s p inal cord injury [J]1J1Neuro surg,2002,96 (Supp11):141-1421
[58]刘郑生 王俊生 王征 等.甲基强的松龙在脊髓型颈椎病外科治疗中的应用价值[J].中国脊柱脊髓杂志2004 14 5 271-274.
[59]Gomes JA Stevens RD Lewin JJ 3rd et al.Glucocorticoid therapy in neurologic critical care[J].Crit Care Med 2005 33 6 1214-1224.
[60]王征,王岩.严重脊髓受压患者围手术期应用甲基强地松龙的临床观察[J].中国脊柱脊髓杂志,2006,16(7)：515-518.
[61]陶春生 倪斌.甲基强的松龙在伴有严重脊髓压迫的颈椎疾患减压术中的应用[J].中国脊柱脊髓杂志2005 15(12)：716--718.
[62]潘胜发 孙宇.大剂量甲基强的松龙在脊髓型颈椎病围手术期应用的探讨[J].中国脊柱脊髓杂志2005 15(12)：719--721.
[63]李宏 李淳德 刘宪义.腰椎手术后应用小剂量甲基强的松龙的安全性观察[J].中国脊柱脊髓杂志2009 19(5)：369—371
[64]张继东 夏群 苗军.甲基强的松龙在脊髓型颈椎病围手术期不同用法的效果观察[J].中国脊柱脊髓杂志2007 17 4 294--296.
[65]李锋 娄玉健 李光辉 等.甲基强的松龙冲击疗法对手术治疗脊髓型颈椎病近期疗效的影响[J].中国脊柱脊髓杂志2006 16 Suppl 23 26.
[66]黄异飞 吴彦生 艾克拜尔 等.大剂量甲基强的松龙在伴有严重脊髓受压的脊髓型颈椎病围手术期的应用[J].中国脊柱脊髓杂志2007 17 6 443--445.
[67]Sekhon LH, Fehlings MG. Epidemiology, demographics,and patho2 physiology of acute spinal cord injury. Spine,2001,26:2
[68]Sauerland M, Phank P, Lacks K, et al. The system analysis of the application of high dose methylprednisolone in the perioperation of surgery[J].Drug Safety,23 (5):449-461.
[69]夏磊,殷铁林等.甲泼尼龙预干预脊髓缺血再灌注损伤对热休克蛋白27和肿瘤坏死因子α表达的影响[J].中华创伤骨科杂志 2009 11 6 555--558
[70]夏磊,杜琳等.甲基强的松龙预处理对缺血再灌注损伤脊髓中热休克蛋白27表达的影响[J].中国脊柱脊髓杂志2009 18 12 939-941
[1]刘渤,廖维宏.脊髓缺血再灌注损伤后神经功能恢复的实验研究.中华创伤杂志,2001,17：359-362
[2]Naidu KA, Fu ES, SuttOn ET, et aL The therapeutic effects of epidural interceUular adhesion molecule-1 monoclonal antibody in a rabbit model:involvement of the intercellular adhesion molecule—1 pathw y in spinal cord ischemiaL [J]. Anesth Analg, 2003,97(3):857—862
[3]杨小玉,朱庆三,赵立君,等.脊髓缺血-再灌注损伤细胞间粘附分子-1及白细胞介素-1β的表达.中国脊柱脊髓杂志,2004,14：167-170
[4]Lin R, Roseborough G, DongY, et a.l DNA damage and repair system in spinal cord ischemia. JVasc Surg,2003,37:847-858
[5]SaderAA, Barbieri-Neto,SaderSL,eta.l The protective action of chlorpromazine on the spinal cord of rabbits submitted to ischemia and reperfusion is dose-dependent. J Cardiovasc Surg(Torino),2002,43:827-831
[6]金惠铭 王建枝等 病理生理学[M]第六版 人民卫生出版社,2004,202--204
[7]Jarasch ED Bruder G, Heid HW. Signif icance of xanth ine oxidase in cap illary enthodelial cells. A cta Physical Scand Supp 1,1986; 548:39
[8]LukacovaN, HalatG, ChavkoM, et a.l Ischemia-reperfusion injury in the spinal cord of rabbits strongly enhances lipid peroxidation andmodifiesphospholipid profiles. Neurochem Res,1996,21:869-873
[9]镇万新,张铁良,黄琪裳,王炳勋.钙阻断剂与激素对实验性脊髓损伤的作用比较.中华骨科杂志,1993,13(6)：439-442.
[10]Young W. Secondary injury mechanisms in acute spinal cord injury. J Emerg Med,1993 11 Suppl 1:13-22.
[11]申才良,江曙,董英海,等.兔脊髓损伤后钠钾钙镁含量变化及临床意义.中国骨伤,1999,12：18-20.
[12]于明琨,朱诚,张光霁,邢宝仁,陈宜张.N—甲基—D—天门冬氨酸受体拮抗剂对猫创伤性脑水肿的影响.中华神经外科杂志,1994,10(2)：79-82.
[13]叶晓健,李家顺,王家林,李明,奚建华.兴奋性氨基酸在脊髓继发性损伤中作用机制的研究.第二军医大学学报,1995,16(6)：520-523.
[14]叶晓健,李明,李家顺,赵定麟,贾连顺.急性脊髓损伤后脑脊液中兴奋性氨基酸含量变化的临床观察.第二军医大学学报,1996,17(6)：531-534.
[15]Olney JW,Ariga TV,Sekine MI,Miyatake TL, Freddo LM,Latov NF.Cytotoxic effects of acidic sulpher containing amino acids on the infant mouse central nervous system. Exp.BrainRes,1971,14(1):61-66.
[16]Panter SS,Gordon EL,Danielsson PE,Nguyen T,Wim HR.Alteration in extracellular amino acids after traumatic spinal cord injury.Ann Neurol,1990,27(1):96-103.
[17]刘连生,廖维宏,刘祚周,陈恒胜,王禾.脊髓损伤及其继发损伤时的兴奋性氨基酸含量变化.中华神经外科杂志,1994,10(20)：70-72.
[18]Watkins JC,Davies J,Evans RH,Francis AA,Jones AW.Pharmacology of receptors for excitatory amino acids.Adv Biochem Psychopharmacol,1981,27:263-273.
[19]Ip WK,Wong CK, Lam CW. Tumour necrosis factor-alpha-in-duced expression of intercellular adhension molecule-1 on human eosinophilic leukaemia Eol-1 cells ismediateded by the activation of nuclear factor-kappaB pathway. Clin Exp Allergy,2003, 33:242-248
[20]Farhood A, McGurie GM, ManningAM, et a.l Intercellular adhensionmolecule 1 expression and its role in neutrophil-induced ischemia-reperfusion injury in rat liver. Leukoc Bio,l 1995,57:368-374
[21]杨惠林,张洪涛,唐天驷,等.缺血再灌注脊髓组织中白细胞介素-8表达的试验研究.苏州大学学报(医学版),2002,22：659-661
[22]朱庆三,尹飞,郭丽,等.脊髓缺血再灌注损伤中神经细胞凋亡的研究.吉林大学学报,2003,29：609-610
[23]Katoh D, Ikau T. Effect of dietary vitamin C on compession injury of the spinal cord in a rat mutantunable to synthesize ascorbic acid and its correlation with that vitamin E[J]. Spine Cord,1996,34 (4):234-245.
[24]章亚东,候树勋,刘英炳,等.脊髓损伤细胞内Ca2+变化及其与脊髓神经功能损害的关系[J].中华骨科杂志,1997,17(5)：291-294
[25]Geisler FH, Dorsey FC, Coleman WP. Past and current clinical stuies with GM1 gangliosidesin acute spinal cord injury[J]. Ann Emerg Med,1993, (6):1041-1047.
[26]Cao X, Tang C, Luo Y. Effect of nerve growth factor on neuronal apoptosis After spinal cord injury in rats[J]. Traumatol, 2002,5 (3):131-135.
[27]Lipton SA, Stamler JS. Actions of redox related congeners of nitricoxide at the NMD A receptor [J].Neuro Pharmacology,1994,33 (3):1299-1308.
[28]Xu J Kim GM Ahmed SH. Glucocorticoid receptor-mediated suppression of acticitor protein -1 activation and matrix metalloproteinase expression after spinal cord injury [J].J Neurosci 2001 21 1 92-97.
[29]王文刚,夏磊,等.早期应用甲基强的松龙上调受损脊髓细胞内hsp27蛋白的表达[J].医药论坛杂志,2007,3：13-15.
[30]Veerkamp JH, Zimmerman AW.Fatty acid-binding proteins of nervous tissue[J]. J Mol neurosci,2001,16(2-3):133-157
[31]张卫红,王道新.脊髓损伤后胶质纤维酸性蛋白的表达及其意义[J] 南京医科大学学 报,22(1)：17-19.
[32]Hoerlein BF, Redding RW, Hof EJ, et al. Evaluation of naloxone, crocetin, thyrotropine releasing hormone, methylprednisolone, partial myelotomy,and hemilaminectomy in the treatment of acute spinal cord trauma[J]. J Am Animal Hosp Assoc,1984,21:67-77.
[33]Goodman LS, Gilman AG Goodman and Gilman's the pharmacological basis of therapeutics, ed7.New York:Macmillan,1985,pp 1459-1489.
[34]Braughler JM,Hall ED. Uptake and elimination of methylprednisolone from c ontused cat spinal cord following intravenous injection of the sodium succinate e ster[J].J Neurosurg,1983,58(4):538-542.
[35]YoungW1Methylp rednis ol one and s p inal cord injury [J]1J1Neuro surg,2002,96 (Supp 11):141-1421
[36]刘郑生 王俊生 王征 等.甲基强的松龙在脊髓型颈椎病外科治疗中的应用价值[J].中国脊柱脊髓杂志2004 14 5 271-274.
[37]Gomes JA Stevens RD Lewin JJ 3rd et al.Glucocorticoid therapy in neurologic critical care[J].Crit Care Med 2005 33 6 1214-1224.
[38]王征,王岩.严重脊髓受压患者围手术期应用甲基强地松龙的临床观察[J].中国脊柱脊髓杂志,2006,16(7)：515-518.
[39]陶春生 倪斌.甲基强的松龙在伴有严重脊髓压迫的颈椎疾患减压术中的应用[J].中国脊柱脊髓杂志2005 15(12)：716--718.
[40]潘胜发 孙宇.大剂量甲基强的松龙在脊髓型颈椎病围手术期应用的探讨[J].中国脊柱脊髓杂志2005 15(12)：719--721.
[41]李宏 李淳德 刘宪义.腰椎手术后应用小剂量甲基强的松龙的安全性观察[J].中国脊柱脊髓杂志 2009 19(5)：369—371
[42]张继东 夏群 苗军.甲基强的松龙在脊髓型颈椎病围手术期不同用法的效果观察[J].中国脊柱脊髓杂志2007 17 4 294--296.
[43]李锋 娄玉健 李光辉 等.甲基强的松龙冲击疗法对手术治疗脊髓型颈椎病近期疗效的影响[J].中国脊柱脊髓杂志2006 16 Suppl 23 26.
[44]黄异飞 吴彦生 艾克拜尔等.大剂量甲基强的松龙在伴有严重脊髓受压的脊髓型颈椎病围手术期的应用[J].中国脊柱脊髓杂志2007 17 6 443--445.
[45]Sekhon LH, Fehlings MG Epidemiology, demographics,and patho2 physiology of acute spinal cord injury. Spine,2001,26:2
[46]夏磊,殷铁林等.甲泼尼龙预干预脊髓缺血再灌注损伤对热休克蛋白27和肿瘤坏死因子α表达的影响[J].中华创伤骨科杂志2009 11 6 555--558
[47]夏磊,杜琳等.甲基强的松龙预处理对缺血再灌注损伤脊髓中热休克蛋白27表达的影响[J].中国脊柱脊髓杂志2009 18 12 939—941
[48]Sauerland M, Phank P, Lacks K, et al. The system analysis of the application of high dose methylprednisolone in the perioperation of surgery[J].Drug Safety,23 (5):449-461.
[49]Moll oy S, Middleton F, Casey A1 Failure t o administer methyl p rednis ol one for acute traumatic spinal cord injury-a prospective audit of 100 patients from a regional spinal injuries unit[J]1 Injury,2002,33:575-5781
[50]ColemanWP, Benzel E, Cahill D, et al1 A critical app raisal of the reporting of the NationalAcute Sp inal Cord Injury Studies (Ⅱ and Ⅲ)ofmethylp rednis ol one in acute s p inal cord injury[J]1 J Sp inalDis ord,2000,13:185
[2]姜建元,顾湘杰.有关脊髓缺血再灌注损伤的几个问题.脊柱外科杂志,2005,01,57-59
[3]Sauerland S,Nagelschmidt M,Mallmann P,et al.Risks and benefits of preoperative high dose methylprednisolone in surgical patients:a systematic review [J].Drug Saf,2000,23 (5):449--461
[4]Bracken MB, Steroids for acute spinal cord injury. Cochrane Database Syst Rev 2002(3):cd001046.
[5]Katircioglu SF, Seren M,Parlar AI,et al. Levosimendan effect on spinal cord ischemia-reperfusion injury following aortic clamping [J]. J Card Surg,2008,23(1): 44-48.
[6]Qayum 1 AK, Janusz M T, Lystir DM, et al. Animal model for investigation of spinal cord injury caused by aoutic ccross-clamp ing. J Invest surg,1997,10:47-52.
[7]伍亚民,王正国,朱佩芳,等.脊髓缺血损伤动物模型及行为的实验研究.中华创伤外科杂志,2000,16：157-159.
[8]镇万新,张铁良,黄琪裳,王炳勋.钙阻断剂与激素对实验性脊髓损伤的作用比较.中华骨科杂志,1993,13(6)：439-442.
[9]Young W. Secondary injury mechanisms in acute spinal cord injury. J Emerg Med,1993, 11 Suppl 1:13-22.
[10]Olney JW, Ariga TV.Cytotoxic effects of acidic sulpher containing amino acids on the infant mouse central nervous system. Exp.BrainRes,1971,14(1):61-66.
[11]Choi DW.Ionic dependence of glutamate neurotoxity.J Neurosci,1987,7(2):369-372.
[12]刘连生,廖维宏.脊髓损伤及其继发损伤时的兴奋性氨基酸含量变化.中华神经外科杂志,1994,10(20)：70-72.
[13]Ip WK,Wong CK, Lam CW. Tumour necrosis factor-alpha-in-duced expression of intercellular adhension molecule-1 on human eosinophilic leukaemia Eol-1 cells ismediateded by the activation of nuclear factor-kappaB pathway. Clin Exp Allergy,2003, 33:242-248
[14]Farhood A, McGurie GM, ManningAM, et a.l Intercellular adhensionmolecule 1 expression and its role in neutrophil-induced ischemia-reperfusion injury in rat liver. Leukoc Bio,l 1995,57:368-374
[15]朱庆三,尹飞,郭丽,等.脊髓缺血再灌注损伤中神经细胞凋亡的研究.吉林大学学报,2003,29：609-610
[16]Cassada DC, Tribble CG, Kaza AK, et a.l Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion. Surgery,2001,130:230-235
[17]Bracken MB, Steroids for acute spinal cord injury. Cochrane Database Syst Rev 2002(3):cd001046.
[18]Bracken MB,Holgord TR, Neurological and functional status 1 year after acute spinal cord injury:estimates of functional recovery in National Acute Spinal Cord Injury Study II from results modeled in National Acute Spinal Cord Injury Study III. J Neurosurg (Spine 3) 2002;96:2 59～66.
[19]Braughler JM,Hall ED. Uptake and elimination of methylprednisolone from contused cat spinal cord following intravenous injection of the sodium succinate ester[J].J Neurosurg, 1983,58(4):538-542.
[20]Michael Costigan, Richard J, Mannion, et al. Heat shock protein 27:evelopmental regulation and expression after peripheral nerve injury.1998,18(15):5891-5901.
[21]Martin JL, Mestril R, Hilal-Dandan R, et al. Small heat shock proteins and protection against ischemic injury in cardiac myocytes. Circulation,1997,96:4343-4348.
[22]Ritossa, F.A new puffing pattern induced and temperature shock and DNP in Drosophila[J] Experientia,1962,18:571-573.
[23]Adams C, et al. Stress protein formation:gene expression and environmental interaction with evolutionary significance. Int Rev Cytol 1982;79:305.
[24]Cotto JJ,Morimoto RJ, et al.Stress-induced activation of the heat-shock response:cell and molecular biology of heat-shock factors.Biochem Soc Symp.1999;64:105-18. Review.
[25]Gernold M, Knauf U, Gaestel M,Stahl J, Kloetzel PM,1993. Development and tissue-specific distribution of mouse small heat shock protein HSP25. Dev Genet 14:103-111.
[26]Wilkinson JM, Pollard I,1993. Immunohistochemical localization of the 25kDa heat shock protein in unstressed rats:Possible functional implications. Anat Rec 237:453-457.
[27]Spector NL, et al.28-kDa mammalian heat shock protein, a novel substrate of a growth regulatory protease involved in differentiation of human leukemia cells. J Biol Chem,1995; 273:1003-1006.
[28]Ciocca DR, Oesterreich S, Chamness GC, Mcguire WL, Fuqua SAW,1993. Biological and clinical implications of heat shock protein 27000(HSP27):a review. J Natl Cancer Inst85:1558-1570.
[29]Lutsch G, Vetter R, Offhauss U, et al. Abundance and location of the small heat shock proteins HSP25 and alphaB-crystallin in rat and human heart. Circulation,1997,96:3466-3476.
[30]Klemenz R, Andres AC, Frohli E, Schafer R, Aoyama A,1993. Expression of the murine small heat shock proteins HSP25 and a b crystallin in the absence of stress .J Cell Biol 120:639-645.
[31]Csermely P, Schnaider T, Soti C, et al. The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. Pharmacol Ther,1998, 79:129-168.
[32]Rutherford SL, et al. Protein folding and the regulation of signaling pathways. Cell,1994;79:1129-1132.
[33]Lstchman DS. Protection of neuronal and cardiac cells by H SP27.Prog Mol Subcell Biol,2002,28 (2):253-265.
[34]刘弈蓉等热休克蛋白27在大鼠脊髓前角中的表达明中国煤炭工业医学杂志.2004,1(7)179-80.
[35]姜苏蓉 刘莉 程蕴琳 热休克蛋白27抗细胞凋亡的分子机制。中华老年医学杂志2004年2月第23卷第2期138-140.
[36]BuchnerJ. HSP90&Co.-a holding for folding[J].Trends BiochemSci,1999,24 (4):136-141.
[37]EllisR J. The molecular chaperone concept[J].Semin Cell Biol,1990,1(1):1-9.
[38]Chamberlain LH, Burgoyne RD. Activation of the ATPase activity of heat-shock proteins Hsc70/HSP70 by cysteine-string protein[J].Biochem J,1997,32 2(R3):853-858.
[39]Koide T, Asada S, Nagata K.Substrate recognition of collagen-specificmolecular chaperone HSP47. Structural requirements and binding regulation [J].J Biol Chem,1999, 274(49):34523-34526.
[40]AsadaS, Koide T, Yasui H, Nagata K. Effect of HSP47 on proly14-hydroxylation of collagen model peptides [J].Cell Struct Funct,1999,24(4):187-196.
[41]Lambert H, Charette SJ, Bernier AF, et al. HSP27 multimerization mediated by phosphorylation-sensitive intermolecular interactions at the amino terminus [J].J Biol Chem,1999,274(14):9378-9385.
[42]Preville X, Salvemini F, Giraud S. Mammalian small stress proteins protect against oxidative stress through their ability to increase glucose-6-phosphate dehydrogenase activity and by maintaining optimal cellular detoxifying machinery[J].Exp Cell Res,19 99,247(1):61-78.
[43]Arrigo AP. Small stress proteins:chaperones that acts as regulators of intracellular redox state and programmed cell death. Biol Chem,1998,379(1):19-26.
[44]Mehlen P, Kretz-Remy C, Preville X, et al. Human HSP27, Drosophila HSP27, or human a b-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFa-induced cell death. EMBO J,1996,15:2695-2706.
[45]SakuraiM,Hayashi T,Abe K,et al.Delayed selective motor neuron death and fas antigen induction after spinal cord ischemia in rabbits [J]. Brain Res,1998,79 7:23 -28.
[46]Leskovar A, Moriarty L J, Turek JJ,et al. The macrophage in acute neural injury: changes in cell numbers over time and levels of cytokine production in mammalian central and peripheral nervous systems[J]. J Exp Biol,2000,203:1783-1795.
[47]Paul,C ,Manero,F, et al.HSP27 as a negative regulator of cytochrome C release [J].Molecular and Cellular Biology2002,22:816-834.
[48]Garrido,C ,Bruey, J- M, et al.HSP27 inhibits cytochrome c-dependent activation of procaspase-9 FASEB Journal 1999,13:2061-2070
[49]Bracy,J- M,Ducasse,C ,Bonniaud,P,et al. HSP27 negatively regulates cell death by interacting with cytochrome [J].Nature Cell Biology 2000,2:645-652.
[50]Marcus J.D Wagstaff; Yolanda Collago-Moraes; Benjamin S.Aspey, et al, Focal cerebral ischaemia increases the levels of several classes of heat shock proteins and their corresponding mRNAs Molecular Brain Research 42(1996):236-244.
[51]Hiroyuki Kato; Kyuya Kogure; Xiao-Hong Liu; et al. Immunohistochemical localization of the low molecular weight stress protein HSP27 following focal cerebral ischemia in the rat Brain research 679(1995):1-7.
[52]R. William Currie, Julie A. Ellison, Ray F. White, Giora Z. Feuerstein, b b,Xinkang Wang, Frank C. Barone Benign focal ischemic preconditioning induces neuronal HSP70 and prolonged astrogliosis with expression of HSP27. Brain Research 863(2000)169-181.
[53][53] Cuesta R, Laroia G, Schneider RJ. Chaperone hsp27 inhibits translation during heat shock by binding eIF4G and facilitating dissociation of cap-initiation complexes Genes Dev,2000,14(12):1460-1470.
[54]Xu J Kim GM Ahmed SH. Glucocorticoid receptor-mediated suppression of acticitor protein -1 activation and matrix metalloproteinase expression after spinal cord injury [J].J Neurosci 2001 21 1 92-97.
[55]Veerkamp JH, Zimmerman AW.Fatty acid-binding proteins of nervous tissue[J].J Mol neurosci,2001,16(2-3):133-157
[56]Braughler JM,Hall ED. Uptake and elimination of methylprednisolone from c ontused cat spinal cord following intravenous injection of the sodium succinate e ster[J].J Neurosurg, 1983,58(4):538-542.
[57]YoungWlMethylp rednis ol one and s p inal cord injury [J]1J1Neuro surg,2002,96 (Supp11):141-1421
[58]刘郑生 王俊生 王征 等.甲基强的松龙在脊髓型颈椎病外科治疗中的应用价值[J].中国脊柱脊髓杂志2004 14 5 271-274.
[59]Gomes JA Stevens RD Lewin JJ 3rd et al.Glucocorticoid therapy in neurologic critical care[J].Crit Care Med 2005 33 6 1214-1224.
[60]王征,王岩.严重脊髓受压患者围手术期应用甲基强地松龙的临床观察[J].中国脊柱脊髓杂志,2006,16(7)：515-518.
[61]陶春生 倪斌.甲基强的松龙在伴有严重脊髓压迫的颈椎疾患减压术中的应用[J].中国脊柱脊髓杂志2005 15(12)：716--718.
[62]潘胜发 孙宇.大剂量甲基强的松龙在脊髓型颈椎病围手术期应用的探讨[J].中国脊柱脊髓杂志2005 15(12)：719--721.
[63]李宏 李淳德 刘宪义.腰椎手术后应用小剂量甲基强的松龙的安全性观察[J].中国脊柱脊髓杂志2009 19(5)：369—371
[64]张继东 夏群 苗军.甲基强的松龙在脊髓型颈椎病围手术期不同用法的效果观察[J].中国脊柱脊髓杂志2007 17 4 294--296.
[65]李锋 娄玉健 李光辉 等.甲基强的松龙冲击疗法对手术治疗脊髓型颈椎病近期疗效的影响[J].中国脊柱脊髓杂志2006 16 Suppl 23 26.
[66]黄异飞 吴彦生 艾克拜尔 等.大剂量甲基强的松龙在伴有严重脊髓受压的脊髓型颈椎病围手术期的应用[J].中国脊柱脊髓杂志2007 17 6 443--445.
[67]Sekhon LH, Fehlings MG. Epidemiology, demographics,and patho2 physiology of acute spinal cord injury. Spine,2001,26:2
[68]Sauerland M, Phank P, Lacks K, et al. The system analysis of the application of high dose methylprednisolone in the perioperation of surgery[J].Drug Safety,23 (5):449-461.
[69]夏磊,殷铁林等.甲泼尼龙预干预脊髓缺血再灌注损伤对热休克蛋白27和肿瘤坏死因子α表达的影响[J].中华创伤骨科杂志 2009 11 6 555--558
[70]夏磊,杜琳等.甲基强的松龙预处理对缺血再灌注损伤脊髓中热休克蛋白27表达的影响[J].中国脊柱脊髓杂志2009 18 12 939-941
[1]刘渤,廖维宏.脊髓缺血再灌注损伤后神经功能恢复的实验研究.中华创伤杂志,2001,17：359-362
[2]Naidu KA, Fu ES, SuttOn ET, et aL The therapeutic effects of epidural interceUular adhesion molecule-1 monoclonal antibody in a rabbit model:involvement of the intercellular adhesion molecule—1 pathw y in spinal cord ischemiaL [J]. Anesth Analg, 2003,97(3):857—862
[3]杨小玉,朱庆三,赵立君,等.脊髓缺血-再灌注损伤细胞间粘附分子-1及白细胞介素-1β的表达.中国脊柱脊髓杂志,2004,14：167-170
[4]Lin R, Roseborough G, DongY, et a.l DNA damage and repair system in spinal cord ischemia. JVasc Surg,2003,37:847-858
[5]SaderAA, Barbieri-Neto,SaderSL,eta.l The protective action of chlorpromazine on the spinal cord of rabbits submitted to ischemia and reperfusion is dose-dependent. J Cardiovasc Surg(Torino),2002,43:827-831
[6]金惠铭 王建枝等 病理生理学[M]第六版 人民卫生出版社,2004,202--204
[7]Jarasch ED Bruder G, Heid HW. Signif icance of xanth ine oxidase in cap illary enthodelial cells. A cta Physical Scand Supp 1,1986; 548:39
[8]LukacovaN, HalatG, ChavkoM, et a.l Ischemia-reperfusion injury in the spinal cord of rabbits strongly enhances lipid peroxidation andmodifiesphospholipid profiles. Neurochem Res,1996,21:869-873
[9]镇万新,张铁良,黄琪裳,王炳勋.钙阻断剂与激素对实验性脊髓损伤的作用比较.中华骨科杂志,1993,13(6)：439-442.
[10]Young W. Secondary injury mechanisms in acute spinal cord injury. J Emerg Med,1993 11 Suppl 1:13-22.
[11]申才良,江曙,董英海,等.兔脊髓损伤后钠钾钙镁含量变化及临床意义.中国骨伤,1999,12：18-20.
[12]于明琨,朱诚,张光霁,邢宝仁,陈宜张.N—甲基—D—天门冬氨酸受体拮抗剂对猫创伤性脑水肿的影响.中华神经外科杂志,1994,10(2)：79-82.
[13]叶晓健,李家顺,王家林,李明,奚建华.兴奋性氨基酸在脊髓继发性损伤中作用机制的研究.第二军医大学学报,1995,16(6)：520-523.
[14]叶晓健,李明,李家顺,赵定麟,贾连顺.急性脊髓损伤后脑脊液中兴奋性氨基酸含量变化的临床观察.第二军医大学学报,1996,17(6)：531-534.
[15]Olney JW,Ariga TV,Sekine MI,Miyatake TL, Freddo LM,Latov NF.Cytotoxic effects of acidic sulpher containing amino acids on the infant mouse central nervous system. Exp.BrainRes,1971,14(1):61-66.
[16]Panter SS,Gordon EL,Danielsson PE,Nguyen T,Wim HR.Alteration in extracellular amino acids after traumatic spinal cord injury.Ann Neurol,1990,27(1):96-103.
[17]刘连生,廖维宏,刘祚周,陈恒胜,王禾.脊髓损伤及其继发损伤时的兴奋性氨基酸含量变化.中华神经外科杂志,1994,10(20)：70-72.
[18]Watkins JC,Davies J,Evans RH,Francis AA,Jones AW.Pharmacology of receptors for excitatory amino acids.Adv Biochem Psychopharmacol,1981,27:263-273.
[19]Ip WK,Wong CK, Lam CW. Tumour necrosis factor-alpha-in-duced expression of intercellular adhension molecule-1 on human eosinophilic leukaemia Eol-1 cells ismediateded by the activation of nuclear factor-kappaB pathway. Clin Exp Allergy,2003, 33:242-248
[20]Farhood A, McGurie GM, ManningAM, et a.l Intercellular adhensionmolecule 1 expression and its role in neutrophil-induced ischemia-reperfusion injury in rat liver. Leukoc Bio,l 1995,57:368-374
[21]杨惠林,张洪涛,唐天驷,等.缺血再灌注脊髓组织中白细胞介素-8表达的试验研究.苏州大学学报(医学版),2002,22：659-661
[22]朱庆三,尹飞,郭丽,等.脊髓缺血再灌注损伤中神经细胞凋亡的研究.吉林大学学报,2003,29：609-610
[23]Katoh D, Ikau T. Effect of dietary vitamin C on compession injury of the spinal cord in a rat mutantunable to synthesize ascorbic acid and its correlation with that vitamin E[J]. Spine Cord,1996,34 (4):234-245.
[24]章亚东,候树勋,刘英炳,等.脊髓损伤细胞内Ca2+变化及其与脊髓神经功能损害的关系[J].中华骨科杂志,1997,17(5)：291-294
[25]Geisler FH, Dorsey FC, Coleman WP. Past and current clinical stuies with GM1 gangliosidesin acute spinal cord injury[J]. Ann Emerg Med,1993, (6):1041-1047.
[26]Cao X, Tang C, Luo Y. Effect of nerve growth factor on neuronal apoptosis After spinal cord injury in rats[J]. Traumatol, 2002,5 (3):131-135.
[27]Lipton SA, Stamler JS. Actions of redox related congeners of nitricoxide at the NMD A receptor [J].Neuro Pharmacology,1994,33 (3):1299-1308.
[28]Xu J Kim GM Ahmed SH. Glucocorticoid receptor-mediated suppression of acticitor protein -1 activation and matrix metalloproteinase expression after spinal cord injury [J].J Neurosci 2001 21 1 92-97.
[29]王文刚,夏磊,等.早期应用甲基强的松龙上调受损脊髓细胞内hsp27蛋白的表达[J].医药论坛杂志,2007,3：13-15.
[30]Veerkamp JH, Zimmerman AW.Fatty acid-binding proteins of nervous tissue[J]. J Mol neurosci,2001,16(2-3):133-157
[31]张卫红,王道新.脊髓损伤后胶质纤维酸性蛋白的表达及其意义[J] 南京医科大学学 报,22(1)：17-19.
[32]Hoerlein BF, Redding RW, Hof EJ, et al. Evaluation of naloxone, crocetin, thyrotropine releasing hormone, methylprednisolone, partial myelotomy,and hemilaminectomy in the treatment of acute spinal cord trauma[J]. J Am Animal Hosp Assoc,1984,21:67-77.
[33]Goodman LS, Gilman AG Goodman and Gilman's the pharmacological basis of therapeutics, ed7.New York:Macmillan,1985,pp 1459-1489.
[34]Braughler JM,Hall ED. Uptake and elimination of methylprednisolone from c ontused cat spinal cord following intravenous injection of the sodium succinate e ster[J].J Neurosurg,1983,58(4):538-542.
[35]YoungW1Methylp rednis ol one and s p inal cord injury [J]1J1Neuro surg,2002,96 (Supp 11):141-1421
[36]刘郑生 王俊生 王征 等.甲基强的松龙在脊髓型颈椎病外科治疗中的应用价值[J].中国脊柱脊髓杂志2004 14 5 271-274.
[37]Gomes JA Stevens RD Lewin JJ 3rd et al.Glucocorticoid therapy in neurologic critical care[J].Crit Care Med 2005 33 6 1214-1224.
[38]王征,王岩.严重脊髓受压患者围手术期应用甲基强地松龙的临床观察[J].中国脊柱脊髓杂志,2006,16(7)：515-518.
[39]陶春生 倪斌.甲基强的松龙在伴有严重脊髓压迫的颈椎疾患减压术中的应用[J].中国脊柱脊髓杂志2005 15(12)：716--718.
[40]潘胜发 孙宇.大剂量甲基强的松龙在脊髓型颈椎病围手术期应用的探讨[J].中国脊柱脊髓杂志2005 15(12)：719--721.
[41]李宏 李淳德 刘宪义.腰椎手术后应用小剂量甲基强的松龙的安全性观察[J].中国脊柱脊髓杂志 2009 19(5)：369—371
[42]张继东 夏群 苗军.甲基强的松龙在脊髓型颈椎病围手术期不同用法的效果观察[J].中国脊柱脊髓杂志2007 17 4 294--296.
[43]李锋 娄玉健 李光辉 等.甲基强的松龙冲击疗法对手术治疗脊髓型颈椎病近期疗效的影响[J].中国脊柱脊髓杂志2006 16 Suppl 23 26.
[44]黄异飞 吴彦生 艾克拜尔等.大剂量甲基强的松龙在伴有严重脊髓受压的脊髓型颈椎病围手术期的应用[J].中国脊柱脊髓杂志2007 17 6 443--445.
[45]Sekhon LH, Fehlings MG Epidemiology, demographics,and patho2 physiology of acute spinal cord injury. Spine,2001,26:2
[46]夏磊,殷铁林等.甲泼尼龙预干预脊髓缺血再灌注损伤对热休克蛋白27和肿瘤坏死因子α表达的影响[J].中华创伤骨科杂志2009 11 6 555--558
[47]夏磊,杜琳等.甲基强的松龙预处理对缺血再灌注损伤脊髓中热休克蛋白27表达的影响[J].中国脊柱脊髓杂志2009 18 12 939—941
[48]Sauerland M, Phank P, Lacks K, et al. The system analysis of the application of high dose methylprednisolone in the perioperation of surgery[J].Drug Safety,23 (5):449-461.
[49]Moll oy S, Middleton F, Casey A1 Failure t o administer methyl p rednis ol one for acute traumatic spinal cord injury-a prospective audit of 100 patients from a regional spinal injuries unit[J]1 Injury,2002,33:575-5781
[50]ColemanWP, Benzel E, Cahill D, et al1 A critical app raisal of the reporting of the NationalAcute Sp inal Cord Injury Studies (Ⅱ and Ⅲ)ofmethylp rednis ol one in acute s p inal cord injury[J]1 J Sp inalDis ord,2000,13:185