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刘志恒

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脊髓缺血再灌注损伤的实验研究
硕士研究生
:刘志恒
     
:罗卓荆 教授
第四军医大学西京医院骨科,西安 710032
 
脊髓损伤发生率高,造成的后果严重,不仅给患者带来生理上和心里上的巨大创伤,也为家庭及社会带来许多问题。脊髓损伤后的损伤机制及进展过程已被逐渐揭示,相关的药物治疗也在不断发展,但依旧没有一种有效而又廉价的药物或是治疗方法。
脊髓损伤过程中存在着众多损伤机制,其中缺血再灌注损伤尤其受到关注,无论是在脊髓本身的创伤还是在其他的医源性损伤中,都扮演着重要的角色。目前临床上应用较广,并受到权威推荐的治疗脊髓损伤的药物是MPGM-1,但单独使用往往带来许多严重的并发症,根据MP的作用特性和经济成本,结合维生素C在体内的广泛作用,联合使用可能会带来较好的治疗效果,并能避免相关并发症的发生。在临床上还有部分患者(1.5%-3%)在接受了脊髓减压手术后,可出现不明原因的进行性脊髓功能丧失,目前多考虑与减压局部脊髓缺血--再灌注损伤有关。观察MP与维生素C联合使用的治疗效果,评估其疗效,并研究慢性脊髓压迫减压后的缺血再灌注损伤程度,讨论其损伤机制。
1.探讨小剂量甲基强的松龙与维生素C联用对兔急性脊髓缺血再灌注损伤模型的保护作用。
2.探讨缺血再灌注损伤是否为慢性脊髓压迫症减压后不明脊髓功能丧失的致伤因素。
第一部分 维生素C与小剂量激素联用对急性脊髓缺血再灌注损伤的保护作用
成年新西兰白兔144只,随机平均分为6组:A组(阴性对照组)、B组(缺血再灌注组)、C组(小剂量MP组)、D组(Vc组)、E(大剂量MP组)、F组(MP+Vc组)。夹闭腹主动脉25 min后移除动脉夹造成缺血再灌注模型,随即给予相应的处理。于再灌注30 min6122448 h每组各取4只动物,检测丙二醛MDA、过氧化氢酶CAT、超氧化物歧化酶SOD、谷胱甘肽过氧物酶GSH-Px表达水平;每组取4只动物于麻醉清醒即刻、再灌注2448 hTarlov 评分系统行后肢运动功能评分,并于48 h评分完毕后取材行HE染色及TUNEL凋亡染色。
第二部分 慢性脊髓压迫减压后的缺血再灌注损伤
成年新西兰白兔96只,随机分为A组(假手术组),B组(缺血再灌注组),C组(慢性压迫减压组)。于0h30min6h12h24h48h每组各取4只动物,检测MDACATSODGSH-Px表达水平;各组于0h48h各取4只动物取材行凋亡细胞计数。
第一部分AEFMDACATSODGSH-Px于再灌注30 min61224 h表达水平明显低于BCD组,且AEF 3组间无明显差异;Tarlov 评分结果提示E3.25±0.43)、F3.50±0.50)组明显优于B2.00±0.71)、C2.50±0.50)、D2.50±0.50)组;HE染色及TUNEL凋亡染色观察E组(29.68±4.57%F组(30.50±4.40%损伤程度及细胞凋亡指数相当,均明显低于其他组。
第二部分BMDACATSODGSH-Px30min6h12h24h表达水平明显高于A组;CMDACATSODGSH-Px于各时间点表达水平均明显高于A组,且C组组间各时间点表达水平无明显区别;C0h48hTUNEL阳性细胞数量无明显差异。
1.小剂量MPVc联合应用对急性脊髓缺血再灌注有明显的保护作用,且效果与大剂量MP相当,避免大剂量激素应用发生并发症的风险。
2.慢性脊髓压迫减压后减压局部并无明显缺血再灌注损伤标志,缺血再灌注并非减压后脊髓功能丧失的原因。
 
 
 
关键词:脊髓损伤;缺血再灌注损伤;甲泼尼龙;维生素C
慢性脊髓压迫


 
Ischemia/Reperfusion after Spinal Cord Injury
Candidate for master: Liu Zhiheng
Supervisor: Luo Zhuojing
Department of Orthopaedics, Xijing hospital, Fourth Military Medical University,
Xi’an 710032, China
 
spinal cord injury has a high incidence, resulting in serious consequences, not only bring physical and psychological problems, but also bring many family and society problems. The mechanism and the process of spinal cord injury has been gradually revealed, and the development of drug treatment has achieved some success, but we still need some effective and inexpensive drugs.
A number of mechanisms happened in spinal cord injury and ischemia/reperfusion injury is particularly concerned. I/R injury plays an important role both in the spinal cord injury and other iatrogenic injuries. MP and GM-1 were recommended as a treatment after spinal cord injury, but their application in clinical often bring many potential complications. According to the pharmacological characteristics and economic costs of MP, combined with extensive effect of vitamin C in the body, the co-application may be a good choice, and to avoid potential complications. And some patients (1.5% -3%) can occur with unexplained loss of spinal function after received spinal decompression surgery, some researchers hold the opinion that it was caused by I/R injury happened in decompression tissue. Compare the efficacy of MP alone with co-application of vitamin C combined with MP, investigate I/R injury after decompression of chronic spinal cord compression, discuss the injury mechanism.
1 To investigate the protection of co-application of low dose MP and ascorbic acid in I/R model.
2 To investigate I/R injury after spinal cord decompression.
Part 1  The protection of co-application MP and ascorbic acid in acute spinal cord I/R injury model
Spinal cord ischemia model was induced by clamping the infrarenal aortic for 25 min. 144 New Zealand white rabbits were randomized as follows: A(negative control group)BI/R group)、C(low-dose MP)DVc)、Ehigh-dose MP group)、FMP+Vc.Each group was given the corresponding disposal. The neurological scoreMDASODCATGDH-Px levels were detected at different time pointH&E and Tunel stains were observed at 48h.
Part 2  Ischemia / reperfusion injury after decompression in chronic spinal cord compression
96 New Zealand white rabbits were randomized as follows: A (negative control group), BI/R group), CDecompression group). MDASODCATGDH-Px were detected at 0h, 30min, 6h, 12h, 24h, 48h. Apoptosis cell numbers were analysis at 0h and 48h.
Results
Part 1: MDASODCATGDH-Px levels in groupAEF at different time were significantly decreased. but there were no significant difference among group AEFTarlov scores of group EF show significantly increase compared with group C and DAnd H&E and Tunel stains show group E and F have the similar injury extent during I/R compared with group BC and D.
Part 2: MDASODCAT and GSH-Px levels in group B were significantly increased compared with group A at 30min, 6h, 12h, 24h, the levels in Group C were significantly increased compared with group A at each time point, and there were no difference in group C; Tunel stain shows the apoptosis cell number has no significant difference between 0h and 48h in group C.
1 The co-application of low dose MP and ascorbic acid shows the same therapeutic effect to spinal cord ischemia-reperfusion compared with large dose MP.
2 There were no significant I/R injury after spinal cord decompression, I/R injury was not the cause of disfunction after spinal cord decompression.
 
 
Key wordsSpinal cord injury; Ischemia-reperfusion; Methylprednisolone;

ascorbic acid; chronic compression

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