胚胎脊髓移植联合甲基强的松龙治疗脊髓损伤的实验研究

目的采用胚胎脊髓移植及大剂量甲基强的松龙联合应用治疗脊髓损伤,观察两者有无协同作用.方法雄性SD大鼠50只,随机分为5组,A、B、C、D组为T12急性脊髓右侧半横断损伤后治疗组,A组给大剂量甲基强的松龙及胚胎脊髓移植联合治疗;B组行大剂量甲基强的松龙治疗;C组行胚胎脊髓移植治疗;D组为单纯损伤;E组为空白对照.治疗后24 h及8周后观察大鼠一般行为及运动功能变化,评分分析.病理观察包括治疗后8周神经纤维记数对比及辣根过氧化物酶示踪观察.结果病理学形态观察示A组损伤区横断面神经纤维记数较B、C、D组明显增多(P＜0.01);A、C组在损伤区注入的辣根过氧化物酶可扩散至损伤区远、近端各约1.0 cm处.除A组左下肢感觉有部分恢复外,无明显行为学改变.结论大剂量甲基强的松龙及胚胎脊髓移植可协同修复损伤脊髓.     

直流电场与甲基强的松龙联合应用治疗急性脊髓损伤的实验研究

目的:探讨直流电场与大剂量甲基强的松龙联合应用治疗完全性急性脊髓损伤的疗效。方法:33只中国家犬随机分成3组,用AllenWD法致脊髓损伤。A组为对照组;B组为脊髓损伤后6h置入电刺激器组;C组为脊髓损伤后2h静滴大剂量甲基强的松龙,脊髓损伤后6h再置入电刺激器组。观察各组伤后1、2、3个月神经功能、皮层体感诱发电位、神经元数量、神经元截面积和尼氏体密度。结果:B、C组各项指标均优于同时期A组(P<0.05或P<0.01),C组优于B组,差异有显著性意义。结论:直流电场与大剂量甲基强的松龙联合应用能协同治疗急性脊髓损伤,更好地促进神经功能早期恢复。     

大剂量甲基强的松龙冲击疗法治疗急性脊髓损伤

Youg[1](1982)应用大剂量甲基强的松龙(Methyl-prednisolone)静脉内注射治疗实验性动物急性脊髓损伤发现,该药可改善损伤后脊髓血流和微血管灌注。Hall[2]用大剂量可的松动物实验性治疗得出类似结果。Bracken等[3]在近期病人随机对比研究中证明,在急性脊髓损伤8h内给予大剂量甲基强的松龙可使神经功能得到改善,但随访时间短。国内尚未见有关报道。本院从1989年1月～1991年12月,3年间共应用大剂量甲基强的松龙治疗伤后48h内入院的急性脊髓不全损伤20例,收到较好效果。本文着重分析给药时间与疗效的关系。1临床资料 本组20例,男15例,女5例;…     

大剂量维生素C与小剂量甲基强的松龙联合治疗大鼠急性脊髓损伤初步研究

目的:研究大剂量维生素C(VitC) 小剂量甲基强的松龙(MP)对大鼠急性脊髓损伤(SCI)的疗效。方法:SD成年大鼠64只,采用Allen法(7g×4cm)在T11造成急性SCI动物模型。动物随机分为:MP治疗组(A组)﹑VitC 1/2MP治疗组(B组)﹑VitC治疗组(C组)﹑对照组(D组)。伤后48h行脊髓形态学检查(HE染色 Olsiwski氏小体染色)、测定脊髓含水量,伤后2周进行行为学检查(斜板实验 Gale评分)。结果:B组SCI后48h脊髓坏死及出血范围明显轻于D组,伤后2周行为学指标优于D组(P<0.05),与A﹑C组相似(P>0.05);伤后48h脊髓含水量明显低于A组﹑C组﹑D组,神经元残存Olsiwski氏小体数量明显高于A组﹑C组及D组(P<0.05)。结论:大鼠急性SCI后早期使用大剂量VitC 小剂量MP具有治疗作用,效果优于单独应用大剂量MP或VitC治疗。     

实验性大鼠胚胎脊髓移植对损伤脊髓影响的观察

目的 建立了一个胚胎脊髓（ｆｅｔａｌ ｓｐｉｎａｌ ｃｏｒｄ）组织的低温保存方法笔一个损伤移植模式。方法 通过病理学、组织化学和免疫组织化学的研究,选用胎龄１４天的Ｗｉｓｔａｒ大鼠,分离胚胎脊髓,逐步降温,最后置于液氮中保存。１５天后取出,快速复温,并植入损伤大鼠脊椎内。全部动物于伤后８周处死。结果 经过低温保存的移植物能够在异体脊髓内存活并与宿主组织融合,其在损伤移植区的胶质细胞增生少于对照组。     

甲基强的松龙预防牵张性脊髓损伤的实验研究

为探索甲基强的松龙（ＭＰ）对牵张性脊髓损伤的防治作用，选用日本大耳白兔４８只，随机分为对照组（Ａ、Ｂ）、实验组（Ｃ、Ｄ）。实验组于伤前３０分钟一次静脉缓慢推注ＭＰ３０ｍｇ／ｋｇ；伤后１５分钟开始，每１小时静脉滴注ＭＰ５．４ｍｇ／ｋｇ，持续５小时。对照组用生理盐水治疗。采用皮质体感诱发电位（ＳＣＥＰ）监护、组织形态学、脊髓组织生化测定、运动功能评定等方法评价。结果表明，Ｃ组、Ｄ组较Ａ组、Ｂ组ＳＣＥＰＰ１波波幅恢复快速、稳定；伤后８小时及１４天运动功能评定其障碍率低于Ａ组、Ｂ组（Ｐ＜０．０５）；脊髓前角灰质神经元体积密度及１００μｍ白质范围内有髓神经纤维数高于Ａ组、Ｂ组（Ｐ＜０．０５）；丙二醛含量低于Ａ组、Ｂ组，过氧化物歧化酶含量高于Ａ组、Ｂ组（Ｐ＜０．０５）；神经元及神经纤维变性、坏死，灰质出血范围及脊髓微血管痉挛程度明显轻于Ａ组、Ｂ组。认为，在脊柱畸形矫正术前应用大剂量ＭＰ，具有预防牵张性脊髓损伤的作用；伤后及时给予ＭＰ，可减轻脊髓继发性损伤     

甲基强的松龙对大鼠急性脊髓损伤后Nogo-A表达的影响

目的：探讨大剂量甲基强的松龙（MP）对急性脊髓损伤（SCI）大鼠脊髓组织中Nogo-A蛋白表达的影响。方法：将56只成年SD大鼠分为正常对照组（A组,n=8）、急性脊髓损伤组（B组,n=24）和急性脊髓损伤后大剂量MP治疗组（C组,n=24）,C组在损伤后早期从尾静脉注射大剂量MP治疗。分别在术后3、7、14d对B、C组大鼠后肢运动功能行BBB评分,再在各时间点处死动物,取受损节段脊髓行HE染色及免疫组化染色观察形态学变化和Nogo-A在脊髓组织中的分布特点;同时应用Western-blot方法测定各组相应时间点Nogo-A表达量,并与A组比较。结果：B、C组大鼠在损伤后各个时间点后肢运动功能均有一定程度的恢复,Nogo-A蛋白在各组大鼠脊髓组织中均呈阳性表达,分布于神经细胞的细胞浆和脊髓神经纤维周围呈包裹神经纤维的状态。B、C组各个时间点Nogo-A表达均显著高于A组（P〈0.05）,7d时最高,14d时的表达量仍高于正常组;C组在各个时间点的表达量显著低于B组,差异有显著性（P〈0.05）。结论：大鼠急性脊髓损伤后Nogo-A显著升高,早期应用大剂量MP对Nogo-A的表达具有明显的抑制作用。     

甲基强的松龙治疗脊髓伤的机制

近20年来，随着对脊髓损伤（spinalcordinjurySCI）基础研究的深入，药物治疗SCI已越来越被外科医师所重视。其中甲基强的松龙（methylprednisoloneMP）在SCIe的应用较为广泛。美国急性脊髓损伤研究会组织第二次多中心临床研究认为MP确实可以促进神经功能的恢复。目前在临床工作中，国内已经有部分医院开始应用大剂量MP治疗急性脊髓伤。本文旨就MP治疗SCI的机制作一综术。众所周知，SCI除包括致伤因素直接造成原发性损伤（primaryinury）外，更重要的是损伤后继发性病理生理改变所造成的继发性损伤（secondaryinjury）。后者是引…     

甲基强的松龙与神经节苷脂治疗大鼠急性脊髓损伤

目的探讨早期联合应用大剂量甲基强的松龙(MP)及神经节苷脂(GM1)对大鼠急性脊髓损伤的治疗效果.方法改良Allen's打击法致伤36只大鼠T10～T12脊髓建立急性脊髓损伤模型,随机分为对照组、MP治疗组(应用大剂量MP)及MP+GM1治疗组(早期联合应用大剂量MP及GM1),观察大鼠肢体功能恢复、运动神经元数目及截面积以及胆碱脂酶活性变化,TUNEL标记检测凋亡神经元细胞,比较各组间差别.结果治疗组大鼠神经元细胞结构退变较对照组轻,BBB评分、运动神经元数目及截面积以及胆碱脂酶(CHE)活性较对照组明显提高,尤以MP+GM1组更明显,脊髓凋亡神经元数对照组较实验组明显增多(P＜0.05).结论甲基强的松龙及神经节苷脂对急性脊髓损伤大鼠的脊髓功能具有保护作用,二者联合应用具有协同作用.     

甲基强的松龙对急性脊髓损伤治疗的药理作用

甲基强的松龙对急性脊髓损伤治疗的药理作用郝定均，周晓渝，袁福镛近年来，大量动物实验和临床研究证明，大剂量甲基强的松龙（ｍｅｔｈｙｌｐｒｅｄｎｉｓｏｌｏｎｅ，ＭＰＳ）可阻止外伤后脊髓的变性及坏死。一组双盲法研究的结果表明，伤后８ｈ内的脊髓损伤患者，２４...     

大鼠胚胎脊髓移植后对损伤脊髓神经营养因子表达的影响

目的：研究大鼠胚胎脊髓移植对损伤脊髓神经营养因子表达的影响。方法：将孕１４ｄ大鼠胚胎脊髓组织移植到成鼠半切洞损伤的脊髓中,手术后采用免疫组织化学技术,对损伤脊髓组织中神经生长因子（ＮＧＦ）、脑源性神经生长因子（ＢＤＮＦ）、神经生长因子３（ＮＴ－３）、睫状神经生长因子（ＣＮＴＦ）进行定量分析。结果：移植组神经营养因子１周、２周、４周、都明显高于单纯损伤组,４周时移植组ＢＤＮＦ表达高于其它各组（Ｐ〈０     

甲基强的松龙辅助直流电场治疗脊髓损伤的实验研究

目的 为弥补脊髓完全损伤后6h置入电刺激器的疗效比伤后立即置入电刺激器的疗效为差这一缺陷，伤后2h应用大剂量甲基强的松龙一次，以减轻或阻止脊髓水肿，提高直流电场的疗效。方法 24只中国家犬随机分成2组，用Allen WD法致脊髓完全损伤。A组为脊髓损伤6h置入电刺激器组；B组脊髓损伤2h静滴大剂量甲基强的松龙，脊髓损伤6h再置入电刺激器组。观察各组伤后1、2、3个月神经功能、皮层体感诱发电位、神经元数量、神经元截面积和尼氏体密度恢复情况。结果 B组上述各项指标均优于同时期A组，差异有显性意义。结论 直流电场的确能有效地促进脊髓再生，辅助使用大剂量甲基强的松龙能更有效地治疗脊髓损伤，特别是促进神经功能早期、更好的恢复。     

Effects of methylprednisolone and dextromethorphan on lipid peroxidation in an experimental model of spinal cord injury

Objective. This study examines the effects of agents purported to improve recovery following spinal cord trauma, methylprednisolone sodium succinate, dextromethorphan, and the combination of both, on the post-traumatic alterations of membrane lipid metabolism. Methods. After sparing ten rats for a control group (G1) and performing T3–T6 laminectomies in 150 rats, spinal cord injuries were accomplished in 120 of 150 Wistar rats with an aneurysmal clip compression at the level of T4-5 for 30 sec. Hence the G2 group (n 30) included the "only laminectomy/sham" group. The 120 injured animals were subdivided into four equal groups (n 30 each). Group G3 underwent no therapy, G4 methylprednisolone (MP), G5 dextromethorphan (DM), and G6 MP+DM therapies. Groups G2–G6 were killed ten by ten at 10 min, 30 min, and 120 min after the operation. We measured tissue (MDA) and blood malonyldialdehyde (MDAb), (a product of lipid peroxidation) levels as an indicator of oxidative damage by thiobarbituric acid method and activity levels of antioxidant enzymes superoxide dismutase and glutathione peroxidase in erythrocytes. Intergroup and intragroup results were compared statistically. Results. Methylprednisolone was able to keep the levels for all parameters close to baseline except for 30-min MDA, MDA_b, and SOD values. But their results were all different from those of G3. Dextromethorphan was successful in this respect at 30-min GSH-Px and 120-min SOD and GSH-Px, and all values were also different from G3 values except for 10-min MDA, SOD, and GSH-Px. Combined therapy was not able to keep levels close to baseline for all parameters, but they were different from G3's except for the GSH-Px values. Methylprednisolone values displayed minimal alterations according to baseline at 120 min. Dextromethorphan was relatively unsuccessful at 10 min. Combined therapy did not show benefit superior to MP/DM single therapies. Electronic Publication     

Somatosensory spinal cord evoked potentials in the evaluation of the effect of dexamethasone in experimental spinal cord injury

We studied the effects of high-dose dexamethasone on amplitude and latency values of spinal cord evoked potentials. Thirty-three rabbits were divided into three equal groups. The first group served as the control group, the others received high-dose (2.5 mg/kg) dexamenthasone, the second group 1 hour prior to and the third group immediately after the induction of a spinal cord trauma in segment T12. The spinal cord evoked potentials were recorded epidurally from T12 segment 5 min before and 5, 30, 60, 90,120 and 150 min after trauma. Pretreatment with dexamethasone (group II) prevented the latency delay, and later treatment with dexemethasone (group III) prevented the latency delay partially.Our results suggest that when dexamethasone is given prophylactially it prevents latency alteration, while treatment with dexamethasone after lesioning prevents latency alteration partially. From our results we conclude that pre-treatment with dexamethasone may involve different mechanisms than were activated in the posttreatment group.     

大鼠脊髓损伤中的细胞凋亡及甲基强的松龙的干预作用

目的：探讨脊髓损伤（SCI）继发损伤机制,研究损伤脊髓细胞的凋亡及其意义,观察甲基强的松龙（MP）对细胞凋亡的影响。方法：使用改良Allen法制作大鼠急性SCI模型,实验分3组,假损伤（脊髓未受打击）,损伤组及MP治疗组,采用HE,荧光Hoechst 33342,TUNEL(末端脱氧核苷转移酶介导的脱氧尿苷三磷酸生物素缺口末端标记技术）等技术观察SCI后4h,8h,3d,7d,14d,21d及28d时损伤中心及邻近节段脊髓细胞的凋亡,治疗组损伤后30min给予大剂量MP,比较MP治疗组与损伤组脊髓细胞凋亡的变化,同时平行观察大鼠神经学和组织学恢复情况及两组神经丝蛋白（NF）含量的变化。结果：假损伤组各检测方法未见脊髓细胞凋亡,损伤组大鼠急性SCI后1d开始出现脊髓细胞凋亡,3d达高峰,自损伤中心向头尾端递减分布,持续21d,MP治疗组在伤后3d及7d凋亡脊髓细胞较损伤组显著减少,神经学恢复及组织学评分较损伤组有显著性提高,结论：凋亡是SCI后脊髓神经元死亡的一种重要方式,在继发性损伤中起极为重要的作用。MP的治疗作用可能与其干预SCI后细胞凋亡有关。     

复方丹参注射液和甲基强的松龙治疗大鼠急性脊髓损伤的作用及机制

目的探讨联合应用复方丹参注射液和甲基强的松龙(MP)对大鼠急性脊髓损伤的治疗作用和意义.方法采用Allen法将64只SD大鼠制成脊髓中度损伤模型,随机分为4组,每组16只,分别给予复方丹参注射液(丹参组)、MP(MP组)、二药联合应用(联合组)及生理盐水(对照组)治疗,观察比较治疗前后动物不同时间的神经功能评分、斜板试验和体感诱发电位,并定量观察受损伤脊髓组织的原位末端标记(TUNEL)阳性细胞数目变化.结果从伤后3周起,治疗组神经功能评分、斜板试验角度以及体感诱发电位与对照组比较差异均有显著性(P＜0.01),联合治疗组与丹参组及激素组比较差异有显著性(P＜0.05).从伤后1周起,丹参组和对照组比较,胶质细胞TUNEL阳性细胞数目显著性减少(P＜0.05).结论复方丹参注射液对大鼠急性脊髓损伤有治疗作用,联合应用复方丹参注射液与MP治疗脊髓损伤具有协同作用.复方丹参注射液可能通过抑制胶质细胞凋亡发挥其治疗作用.     

大剂量甲基强的松龙与东莨菪碱治疗急性脊髓损伤的临床观察

目的比较甲基强的松龙(MP)与东莨菪碱(SCP)治疗急性脊髓损伤(ASCI)的治疗效果.方法将44例ASCI患者随机分为3组,伤后8h以内患者随机分入大剂量MP治疗组及SCP治疗组,受伤时间超过8h的患者分人对照组.分别于入院时、伤后6周和6个月时对脊髓功能进行评分.结果两治疗组的感觉功能在伤后6周和6个月时均有明显好转,运动功能MP治疗组在伤后6周时即有明显好转,而SCP治疗组在伤后6个月时才有明显好转.对照组患者脊髓功能恢复不明显.结论MP与SCP均是治疗ASCI有效的药物,MP能够早期促进运动功能的恢复,对ASCI患者的康复有重要意义.     

脊髓诱发电位的实验研究

为探索脊髓诱发电位（Spinalcordevokednotentials，SCEP）在术中监测的安全范围，将刺激和记录线电极分别置于24只大耳白兔T7～T8、L4～L5间隙硬障外，记录正常电位后对脊髓施加纵向牵张力，至实验要求的波幅。波幅下降至正常的80％组脊髓组织结构轻微改变，脊髓功能正常；下降至50％组及＜50％组则出现不可逆损害。结果表明，SCEP波形稳定，其波幅下降至80％是脊髓损伤的危险信号，下降至50％或50％以下将产生不可逆的脊髓损伤。     

Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury

Spinal cord injury (SCI) results in the loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Methylprednisolone (MP), by reducing edema and protecting the cell membrane against peroxidation, is the only pharmacological agent with a proven clinically beneficial effect on SCI. Melatonin, known as a free radical scavenger, has been shown to have an effect on lipid peroxidation following experimental SCI. The purpose of this study was to examine the effect of MP and melatonin on neurological, ultrastructural, and electrophysiological recovery. Female albino rats weighing 200–250 g were randomized into five groups of 18 rats each and six rats for the control group. Weight-drop trauma was performed for each group and a 30-mg/kg single dose of MP for rats in group 1, a 10-mg/kg single dose of melatonin for rats in group 2, and MP and melatonin in the same doses for rats in group 3 were administered immediately after trauma. The rats in group 4 were the vehicle group (treated with ethanol) and group 5 was the trauma group. The motor and somatosensory evoked potentials were recorded at the 4th hour, the 24th hour, and on the 10th day of the study for six rats in each group. Posttraumatic neurological recovery was recorded for 10 days using motor function score and inclined plane test. After electrophysiological study the rats were terminated for an analysis of lipid peroxidation level of the injured site of the spinal cord. Electron microscopic studies were performed to determine the effects of melatonin, MP, and the combined treatment with MP and melatonin on axons, neurons, myelin, nucleus, and intracytoplasmic edema. The groups treated with MP, melatonin, and a combination of both had significantly enhanced electrophysiological, biochemical, and neurological recovery and also showed better ultrastructural findings than the trauma and vehicle groups. Although combined treatment was significantly more effective on lipid peroxidation than melatonin or MP treatments alone, at the 10th day, neurobehavioral, electrophysiological, and ultrastructural recovery were at the same level. In conclusion, MP, melatonin, and MP and melatonin combined treatment modalities improved functional recovery at the same level. Future studies involving different doses of melatonin and different dose combinations with MP could promise better results since each drug has a different anti-oxidative mechanism of action.Electronic Supplementary Material Supplementary material is available in the online version of this article at The number of references, figures of waveforms obtained from CSEP and MEP tests, and electron micrographs of the samples obtained from trauma and all treatment groups at the 10th day postinjury have been reduced in the printed version. The complete version of the article will be published in the web version of the Journal