甲基强的松龙冲击法治疗急性脊髓损伤的近期观察

目的探讨应用大剂量甲基强的松龙（MP）对急性脊髓损伤（ASCI）近期神经功能恢复的影响。方法2002年8月至2005年8月，对60例急性脊髓损伤患者，根据伤后时间并按照自愿选择用药原则分为应用MP治疗组（A组），12例，男18例，女14例，平均年龄（42．6±6．4）岁和未应用MP对照组（B组），28例，男16例，女12例，平均年龄（39．6±7．8）岁。伤后8h以内患者列入大剂量MP治疗组，受伤时间超过8h的患者列入对照组。以ASIA分级标准进行分级，并比较疗效和并发症。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MP治疗组（A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。结论甲基强的松龙是治疗急性脊髓损伤有效的药物，正确、及时使用MP能够早期促进运动功能的恢复，但未显著增加患者治疗中并发症的发生率。     

汉防己甲素对大鼠急性脊髓损伤的作用及意义

目的：探讨汉防己甲素（Tet）对急性脊髓损伤（ASCI）的保护作用及作用机制。方法：81只大鼠随机分为三组：生盐水对照组（NS组）、汉防己甲素治疗组（Tet组）和甲基强松龙治疗组（MP组），每组27只，用加速型Allen′s打击法制成脊髓急性损伤模型，监测大鼠ASCI后及用药后的血压变化，测定损伤区脊髓Ca^2 、MDA含量；采用氢清除法测定脊髓伤区血流量（SCBF）的变化；连续观测6周ASCI后运动功能评分情况，ASCI后4h,8h、6周取伤区标本进行组织病理检查，结果：ASCI后10s各组动物的MABP显著升高，1min内迅速降至正常水平，之后Tet组舒张压，平均动脉明显降低（P＜0．05），而收缩压降低不明显（P＞0．05）；ASCI后SCBF下降，但Tet组和MP组的SCBF较NS组高（P＜0．05）；损伤区Ca^2 及MDA含量Tet组和MP组均较NS组低，神经功能评分均较NS组高。结论：Tet能改善微循环，防止SCBF的减少；抗脂质过氧化损伤，减少脂质过氧化物MDA的生成；减轻Ca^2 的局部积聚，防止钙超载，阻断继发性损伤的链式反应，减轻组织继发性损伤。对实验性急性脊髓损伤有保护作用。     

大剂量甲基强的松龙对大鼠急性脊髓损伤后神经细胞Bcl-2表达及细胞凋亡的影响

目的：观察大剂量甲基强的松龙（MP）治疗对大鼠急性脊髓损伤（ASCI）后神经细胞凋亡及凋亡基因Bcl-2的影响。方法：选取48只雌性SD大鼠随机等分为2组,对照组与治疗组,按Nystrom法制备大鼠急性脊髓损伤模型。治疗组伤后30min经腹膜腔注入MP30mg／kg,以后每小时腹膜腔注入MP5．4mg／kg,维持24h;对照组应用生理盐水替代MP,处理方法同治疗组。两组分别于伤后4、8h及1、3、7、14d灌注固定后取材。免疫组织化学检测损伤段脊髓内Bcl-2蛋白表达,TUNEL检测细胞凋亡,染色结果应用图像分析仪进行半定量分析。结果：大鼠ASCI后4h即可见脊髓内TUNEL阳性细胞,8h表达达高峰,此后表达量逐渐下降,14d时仍可见少量阳性细胞。凋亡相关蛋白Bcl-2在伤后4h即可见表达,伤后1d达高峰,伤后14d仍有表达,与对照组相比,治疗组伤后8h、1d和3d时凋亡细胞数减少有统计学意义,伤后8h和1d Bcl-2蛋白表达增高有统计学意义。结论：大剂量甲基强的松龙治疗可抑制大鼠ASCI后神经细胞凋亡,并增加凋亡相关蛋白Bcl-2的表达：     

大剂量甲基强的松龙冲击治疗急性脊髓损伤疗效分析

目的研究大剂量甲基强的松龙(MP)治疗急性脊髓损伤的临床效果.方法对87例急性脊髓损伤患者进行回顾性研究,根据伤后时间并按自愿选择用药原则分为应用MP治疗组(MP组,45例)和未应用MP治疗组(对照组,42例),以ASIA分级标准进行分级,并比较疗效和并发症.结果两组患者在治疗前后感觉及运动功能均有明显改善(P＜0.05).但MP组的感觉及运动功能恢复均优于对照组(P＜0.05).MP治疗组中24h治疗组(A组)与48h治疗组(B组)并发症发生率比较无显著性差异(P＞0.05),而MP组与对照组比较并发症的发生率明显增加,有显著性差异(P＜0.05).结论早期应用MP大剂量冲击治疗急性脊髓损伤是一项有效措施,但会显著增加患者治疗中并发症的发生率.     

甲基强的松龙对大鼠脊髓损伤后神经细胞凋亡的影响及其机理

目的研究甲基强的松龙(MP)对大鼠横断性脊髓损伤(SCI)后神经细胞凋亡的影响及其作用机理.方法60只成年Wistar大鼠随机分成正常对照组、脊髓损伤组和MP治疗组,每组20只,MP治疗组在横断T10脊髓组织后30min经尾静脉给予MP治疗,损伤组和对照组未予任何治疗.MP治疗组和脊髓损伤组大鼠于脊髓损伤后8h、24h、3d和1周取材,采用透射电镜、TUNEL染色观察细胞凋亡情况,采用免疫组织化学染色观察Fas、半胱氨酸蛋白酶(caspase)-8和caspase-3在SCI前后的变化情况,采用改良Tarlov评分方法观察大鼠后肢运动功能.结果SCI后24h大鼠后肢运动功能逐渐恢复,MP治疗组大鼠的后肢运动功能恢复优于损伤组,7d后尤其明显.TUNEL染色和电镜检查证实SCI后8h即有凋亡细胞出现,其中既有神经元也有胶质细胞3d凋亡细胞数达到高峰;7d仍有凋亡细胞存在,但已明显减少;各时间点治疗组凋亡细胞数量明显少于损伤组(P＜0.05).治疗组和损伤组在SCI后8h可以检测到少量的Fas和caspase-8阳性神经元及胶质细胞,Fas和caspase-8的表达在SCI后3d达到高峰,7d表达下降,各时间点治疗组的Fas和caspase-8灰度值明显大于损伤组,二者有显著性差异(P＜0.05).治疗组和损伤组caspase-3的表达在SCI后8h均逐渐增加(与对照组相比),7d达到高峰,治疗组灰度值大于损伤组,但二者无显著性差异.结论MP能抑制大鼠脊髓横断性脊髓损伤后的神经细胞凋亡,但不能推迟细胞凋亡出现的高峰时间;MP抑制细胞凋亡的途径可能通过非特异性抑制Fas和caspase-8的表达来实现.     

川芎嗪对大鼠脊髓损伤后神经功能恢复作用的研究

目的探讨川芎嗪(TMP)对大鼠脊髓损伤后后肢运动功能恢复的影响。方法雄性成年SD大鼠24只,随机均分为假手术组、对照组及TMP治疗组。采用改良Allen法建立大鼠胸段脊髓打击模型,HE染色观察伤后4周伤段脊髓残存组织的面积,采用斜板试验和运动功能评分观察大鼠后肢运动功能的恢复情况。结果大鼠脊髓损伤后1～4周,TMP治疗组后肢运动功能评分明显高于对照组,两组间差异有显著性(P<0.05)。伤后4周,TMP组伤段残存脊髓组织的面积大于对照组(P<0.01)。结论TMP能明显减少脊髓损伤后伤区的坏死和萎缩,并促进大鼠后肢运动功能的恢复。     

甲基强的松龙对脊髓爆震伤后运动神经元形态学改变的实验研究

目的观察甲基强的松龙(MP)冲击疗法在脊髓爆震伤后早期救治中的疗效.方法将48只家兔随机分为6h生理盐水组(A组)、24h生理盐水组(B组)、48h生理盐水组(C组)、6h MP组(D组)、24h MP组(E组)及48h MP组(F组),每组8只,采用0.9g黑索金(RDX)对每只家兔进行爆震,伤后1h内A、B、C组给予静脉输入生理盐水,速度为5ml/kg/h,D、E、F组根据NASCISⅡ方案给予MP,A、D组于伤后6h取材,B、E组于伤后24h取材,C、F于伤后48h取材,观察脊髓前角运动神经元的形态和数量的变化.结果爆震伤后6h脊髓运动神经元出现可逆性改变,伤后24h脊髓死亡运动神经元达到最多,并且持续到伤后48h,伤后1h内给予MP冲击治疗后,24h、48h组与对照组相比在正常与坏死神经元的数量方面均表现出显著的统计学差异(P＜0.001).结论脊髓爆震伤后早期给予MP冲击治疗,对脊髓运动神经元具有保护作用.     

重组人促红细胞生成素(rH-EPO)对急性脊髓水肿抑制作用的实验研究

目的研究重组人促红细胞生成素对急性脊髓水肿的抑制作用及其机制探究其临床应用的可能性。方法实验动物随机分为3组,采用静力加载技术于Wistar大鼠T13椎体水平造成急性脊髓损伤。生理盐水对照组,伤后立即给予生理盐水尾静脉注射。rHu-EPO治疗组,动物伤后立即给予rHu-EPO 1000unit/kg of bw尾静脉注射。甲基强的松龙治疗组,伤后立即给予甲基强的松龙30mg/kg of bw尾静脉注射。观察治疗前后实验动物神经功能评分变化、以及脊髓组织含水量的改变,细胞内游离钙含量([Ca2 ]i)的变化。结果(1)较之对照组,rH-EPO治疗组伤后1h运动功能已明显恢复(P<0.01)Rh-EPO治疗组受伤节段含水量在伤后各阶段均明显低于对照组(P<0.01),Rh-EPO在伤后12h对细胞内[Ca2 ]i含量的上升表现出明显的抑制作用(P<0.05)(。2)较之对照组,MP治疗组伤后伤后24h开始出现明显的功能恢复(P<0.05),伤后24h、48h含水量少于对照组(P<0.01),MP在伤后24h对细胞内[Ca2 ]i含量的上升表现出明显的抑制作用(P<0.05)。结论重组人促红细胞生成素对急性脊髓水肿具有明显的抑制作用,并且起效时间早,有效促进急性脊髓水肿时的神经功能恢复。     

大剂量甲基强的松龙对急性脊髓损伤的疗效及预后判断

目的探讨大剂量甲基强的松龙（methylprednisolone,MP）对急性脊髓损伤（acute spinal cord injury,ASCI）的疗效、并发症防治及预后判断。方法将38例ASCI患者根据影像学改变和脊髓功能丧失程度分轻、中、重三度。轻度10例,影像检查无明显异常、脊髓功能部分丧失;中度21例,影像检查轻至中度异常（椎管轻至中度占位,MRI脊髓有信号改变）、脊髓功能部分丧失;重度7例,影像检查重度异常（椎管中至重度占位,MRI显示脊髓断裂）、脊髓功能完全丧失。38例患者在受伤8 h内按NASCIS方案接受MP冲击治疗,分析其疗效和判断预后。结果经6周及6个月随访,MP对轻、中度组患者疗效显著,预后好;重度组疗效及预后差。38例患者住院治疗及随访过程中除1例发生上消化道出血,余无伤口感染、延迟愈合、肺部感染、心率失常等并发症。结论大剂量MP冲击治疗对急性脊髓损伤患者安全有效,对轻、中度患者疗效显著,预后好。     

硫酸软骨素酶ABC促进大鼠脊髓损伤后神经功能恢复的实验研究

目的 探讨硫酸软骨素酶ABC(ChABC)对神经脊髓损伤后运动功能恢复的影响.方法 SD大鼠72只,雌雄不限,随机分为假手术组、生理盐水对照组和ChABC治疗组,采用Allen法打击大鼠胸10脊髓损伤模型,分别在伤后即刻和随后每天一次连续一周蛛网膜下注射生理盐水和ChABC.HE染色和尼氏染色观察各时间点脊髓损伤组织形态和尼氏体及神经元的变化,采用BBB功能评分和运动诱发电位(MEP)观察大鼠的运动功能恢复情况.结果 大鼠脊髓损伤后1周时BBB评分和对照组无显著差别,在2、4周,治疗组评分结果明显优于对照组(P＜0.05;P＜0.01);MEP在1、4周的N1波潜伏期与对照组差异显著(P＜0.05;P＜0.01).HE和Nissl染色显示治疗组的形态和神经元数量要优于对照组.结论 ChABC能促进大鼠脊髓损伤后神经运动功能恢复,并对脊髓组织损伤具有保护作用.     

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。     

纳洛酮治疗急性脊髓损伤的临床观察

作者以甲基强的松龙为参照，观察了１４例急性脊髓损伤患者应用纳洛酮后的神经功能恢复。结果表明，急性脊髓损伤６ｈ内的患者，入院后即在１５ｍｉｎ内通过外周静脉滴注纳洛酮５．４μｇ／ｋｇ，暂停４５ｍｉｎ后以４μｇ／ｋｇ／ｈ维持２３ｈ。给药后６周观察，同对照组相比，纳洛酮治疗患者的触觉、痛觉评分明显提高，同对照组相比，甲基强的松龙组给药后６周及６月观察，运动功能、触觉、痛觉功能评分均显著提高。结论：急性脊髓损伤后６ｈ内外周静脉给予纳洛酮也可改善急性脊髓损伤患者的神经功能，但作用不如甲基强的松龙显著。     

Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study.

The 1-year follow-up data of a multicenter randomized controlled trial of methylprednisolone (30 mg/kg bolus and 5.4 mg/kg/hr for 23 hours) or naloxone (5.4 mg/kg bolus and 4.0 mg/kg/hr for 23 hours) treatment for acute spinal cord injury are reported and compared with placebo results. In patients treated with methylprednisolone within 8 hours of injury, increased recovery of neurological function was seen at 6 weeks and at 6 months and continued to be observed 1 year after injury. For motor function, this difference was statistically significant (p = 0.030), and was found in patients with total sensory and motor loss in the emergency room (p = 0.019) and in those with some preservation of motor and sensory function (p = 0.024). Naloxone-treated patients did not show significantly greater recovery. Patients treated after 8 hours of injury recovered less motor function if receiving methylprednisolone (p = 0.08) or naloxone (p = 0.10) as compared with those given placebo. Complication and mortality rates were similar in either group of treated patients as compared with the placebo group. The authors conclude that treatment with the study dose of methylprednisolone is indicated for acute spinal cord trauma, but only if it can be started within 8 hours of injury.     

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。     

乌司他丁对急性脊髓伤神经细胞保护作用的实验研究

目的研究乌司他丁对急性脊髓损伤大鼠微环境调控的影响及神经功能的预防和保护作用。方法选用SD大鼠80只，采用改良Allen重物打击法制成脊髓损伤模型，随机分为4组：脊髓损伤组（SCI组，n=20）；使用乌司他丁组（U组，n=20）；使用甲基强的松龙组（M组，n=20）；乌司他丁＋甲基强的松龙联合用药组（U＋M组，n=20），所有给药组在脊髓损伤后0．5h、4h、8h、24h、36h、48h、60h、72h给药。在脊髓损伤后24h、72h、1周、2周、3周5个时间段进行神经功能评分、脊髓病理形态学观察。结果使用乌司他丁可明显改善损伤脊髓的病理形态；神经功能评分明显增高。结论大鼠急性脊髓损伤后使用乌司他丁能有效的保护神经细胞，抑制细胞进一步衰亡。     

Sustained spinal cord compression: part II: effect of methylprednisolone on regional blood flow and recovery of somatosensory evoked potentials

BACKGROUND: The efficacy of methylprednisolone in the treatment of traumatic spinal cord injury is controversial. We examined the effect of methylprednisolone on regional spinal cord blood flow and attempted to determine whether recovery of electrophysiological function is dependent on reperfusion, either during sustained spinal cord compression or after decompression. METHODS: The effects of methylprednisolone therapy on recovery of somatosensory evoked potentials and on spinal cord blood flow were examined in a canine model of dynamic spinal cord compression. Methylprednisolone (30 mg/kg intravenous loading dose followed by 5.4 mg/kg/hr intravenous infusion) or saline solution was administered to thirty-six beagles (eighteen in each group) five minutes after cessation of dynamic spinal cord compression and loss of all somatosensory evoked potentials. After ninety minutes of sustained compression, the spinal cords were decompressed. Somatosensory evoked potentials and spinal cord blood flow were evaluated throughout the period of sustained compression and for three hours after decompression. RESULTS: Seven dogs treated with methylprednisolone and none treated with saline solution recovered measurable somatosensory evoked potentials during sustained compression. After decompression, three more dogs treated with methylprednisolone and seven dogs treated with saline solution recovered somatosensory evoked potentials. Four dogs treated with methylprednisolone lost their previously measurable somatosensory evoked potentials. In the methylprednisolone group, spinal cord blood flow was significantly higher (p < 0.05) in the dogs that had recovered somatosensory evoked potentials than it was in the dogs that had not. Reperfusion blood flow was significantly higher (p < 0.05) in the saline-solution group than it was in the methylprednisolone group. Spinal cord blood flow in the saline-solution group returned to baseline levels within five minutes after decompression. It did not return to baseline levels in the dogs treated with methylprednisolone. CONCLUSIONS: The methylprednisolone administered in this study did not provide a large or significant lasting benefit with regard to neurological preservation or restoration. Methylprednisolone may reduce regional spinal cord blood flow through mechanisms affecting normal autoregulatory blood-flow function.     

Effects of dexmedetomidine or methylprednisolone on inflammatory responses in spinal cord injury

Background: The aim of this study was to compare the anti-inflammatory response of methylprednisolone and the α2-agonist dexmedetomidine in spinal cord injury (SCI).
Methods: Twenty-four male adult Wistar albino rats, weight 200–250 g, were included in the study. The rats were divided into four groups as follows: the control group ( n : 6) received only laminectomy; the SCI group ( n : 6) with trauma alone; the SCI+methylprednisolone group ( n : 6) with trauma and 30 mg/kg methylprednisolone, followed by a maintenance dose of 5.4 mg/kg/h; and the SCI+dexmedetomidine group ( n : 6) with trauma and 10 μg/kg dexmedetomidine treatment intraperitoneally. Twenty-four hours after the trauma, spinal cord samples were taken for histopathological examination and serum samples were collected for interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α measurement.
Results: TNF-α ( P =0.009) and IL-6 ( P =0.009) levels were significantly increased in the SCI group. TNF-α and IL-6 levels were significantly decreased with methylprednisolone ( P =0.002, 0.002) and dexmedetomidine ( P =0.002, 0.009) treatment, respectively. Methylprednisolone and dexmedetomidine treatment reduced neutrophils' infiltration in SCI.
Conclusions: The current study does not clarify the definitive mechanism by which dexmedetomidine decreases inflammatory cytokines but it is the first study to report the anti-inflammatory effect of dexmedetomidine in SCI. Further studies are required to elucidate the effects of dexmedetomidine on the inflammatory response.     

脊髓爆震伤后早期治疗神经元的形态学变化

[目的]研究脊髓爆震伤后早期采用不同药物干预对脊髓前角运动神经元影响。[方法]将36只家兔随机分为对照组（A组，n=12）、地塞米松实验纽（B组，n=12）、甲强龙实验组（C组，n=12），每组家兔均采用0．9g单质金属炸药黑索金（cyclotrimethylene trinitramine）进行爆震，伤后各组分别给予静脉输入生理盐水、地塞米松及甲强龙，于伤后6h、24h2个时间点取材，在光镜下观察脊髓前角运动神经元形态和数量的改变。[结果]发现爆震伤后6h脊髓运动神经元出现可逆性改变，伤后24h脊髓死亡运动神经元显著增加，伤后早期给予地塞米松及甲强龙治疗后，死亡神经元的数量减少与对照组相比有显著的统计学意义（P〈0．001），而B、C组之间无显著差别（P〉0．05）。[结论]脊髓爆震伤后早期应用糖皮质激素对运动神经元具有保护作用，在本实验条件下，甲强龙在早期脊髓爆震伤中的疗效与地塞米松相比没有优势。