实验性脊髓损伤后内皮素与前列环素含量的变化及意义

目的：探讨脊髓损伤后脊髓组织中内皮素（ＥＴ）与前列环素（ＰＧＩ２）变化的相互关系与意义。方法：３６只大鼠随机分为６组，Ａｌｅｎｓ法中度量（５０ｇ·ｃｍ）损伤脊髓。测定伤段脊髓中内皮素与６－酮－前列腺素Ｆ１α含量。结果：内皮素含量在伤后３０ｍｉｎ显著升高，２ｈ急剧升高达到高峰，以后逐渐下降；６－酮－前列腺素Ｆ１α含量在伤后３０ｍｉｎ即升高，２ｈ达到较高水平，其升高程度较内皮素小，以后缓慢上升。结论：脊髓损伤早期内皮素含量的急剧升高和前列环素的相对不足可能与脊髓损伤后早期缺血的产生有关，内皮素可能通过多种途经参与脊髓损伤后的继发损伤     

脊髓损伤后低剂量FK506对伤段组织电解质水含量失衡的早期保护作用

[目的]探讨脊髓损伤后早期应用低剂量抗移植排斥药物—FK506对伤段脊髓组织钙、镁离子及水含量的影响,明确其神经保护作用的可能机制。[方法]35只雄性Wistar大鼠随机分为对照组、损伤组和治疗组。采用Allen＇s打击法制作脊髓损伤模型,对照组仅做椎板切除术。治疗组在脊髓损伤后5min一次性经尾静脉注射FK506（0.3mg/kg）,其余两组以相同方法给予0.9%的生理盐水。术后6、12、24h取材,采用干湿法测定伤段脊髓组织水含量,以原子吸收光谱分析法测定钙、镁离子含量。[结果]伤段脊髓组织中水含量及钙离子水平升高,两者均于伤后12h达高峰,而镁离子水平降低,应用FK506可显著改善上述变化（P〈0.05,P〈0.01）。[结论]低剂量FK506可减轻伤段脊髓组织水肿和电解质失衡,对继发性脊髓损伤具有神经保护作用。     

尾静脉注射bFGF对大鼠脊髓损伤的早期影响

目的:比较不同途径应用碱性成纤维细胞生长因子(basicfibroblastgrowthfactor,bFGF)对大鼠脊髓损伤早期水、钙、镁离子的影响,探讨静脉应用bFGF的可行性。方法:AllenWD(Weightdrop)技术,以10g×25cm致伤力造成大鼠T8急性脊髓不完全损伤,不同途径用药比较。术后2h、6h及24h切取伤区脊髓组织检测水、钙、镁离子变化。结果:受损伤脊髓组织水含量增多,钙离子水平增高,镁离子水平下降,而蛛网膜下腔应用bFGF及尾静脉注射bFGF均能明显改变上述变化。结论:脊髓损伤早期静脉应用bFGF同样对脊髓损伤具有保护作用。     

早期补镁对脊髓损伤后继发性脊髓水肿的影响

目的：探讨镁对脊髓损伤后继发性水肿的影响。方法：按改良的Ａｌｌｅｎ’ｓ重物打击法制备兔脊髓损伤模型,将动物分为５组,Ａ组为正常对照组;Ｂ、Ｄ组分别为损伤后２４ｈ和４８ｈ不用镁组;Ｃ、Ｅ组分别为损伤后２４ｈ及４８ｈ用镁组,于脊髓损伤后３０ｍｉｎ一次性给予硫酸镁（６００ｍｇ／ｋｇ,皮下注射）。分别取材测定伤段脊髓组织水、钙、镁含量及观察局部的组织病理学改变。结果：各损伤组脊髓组织含水量显著高于正常对照     

磁刺激和碱性成纤维细胞生长因子对脊髓损伤早期的保护作用

目的探讨脊髓损伤后，应用磁刺激和外源性碱性成纤维细胞生长因子(bFGF)对损伤脊髓组织早期的保护作用。方法实验利用Allen WD(weight drop)技术，以致伤力(砝码质量10g，下落高度2．5cm)制成wistar大鼠T8脊髓损伤模型，治疗组分别于术后即刻、1h、2h、4h、24h分别予0．5HZ、70％输出强度的磁刺激，同时经蛛网膜下腔导管注入20ul bFGF，对照组不做处理。术后2h、6h、24h取治疗组、对照组动物损伤区脊髓组织作以下检测：用干湿法测水含量；用原子吸收光谱法测钙、镁离子含量；伤后5d取损伤脊髓组织，电镜观察脊髓结构。结果损伤区脊髓组织水含量增多，钙离子水平升高，镁离子水平下降，白质内髓鞘结构紊乱，囊性变严重；而应用磁刺激和bFGF可改善上述变化。结论脊髓损伤后应用磁刺激和bFGF可减轻脊髓损伤后的离子失衡，从而对继发性脊髓损伤具有保护作用。     

醒髓汤抑制脊髓继发性损伤的实验研究

目的：研究中药复方醒髓汤对于脊髓损伤后兴奋性氨基酸诱发神经毒效应的抑制作用。方法：80只SD大鼠随机分成3组,用AllenWD法致脊髓不完全性损伤,对照组（A组,18只）切除椎板,不损伤脊髓,不给药;模型(B组,26只）造模前后30min应用蒸馏水2ml灌胃,治疗组分成造模前30min给药组（C1组,18只）及30min后给药组（C2组,18只）,按12．5g.kg^-1.d^-1剂量分2次给药。于用药后50min取伤段脊髓标本,纸上电泳法检测其兴奋性氨基酸含量;于造模后24h取伤段脊髓标本,干湿重法测定水含量;原子吸收光谱法测定离子含量;于造模后72h取脊髓标本进行光,电镜观察。结果：同A组比较,B组脊髓组织兴奋性氨基酸含量早期显著增高（P＜0．05）,而后期无显著性差异（P＞0．05）,早期B组相比,C1组脊髓组织兴奋性氨基酸含量显著降低（P＜0．01）;组织细胞变性坏死严重,同B组相比,C1组脊须组织兴奋性氨基酸含量显著降低（P＜0．01）,水钠,钾,钙含量显著减少（P＜0．01）,钾,镁含量显著增高（P＜0．01）,脊髓组织变性坏死轻,同B组比较,C2组脊髓组织兴奋性氨基酸含量无显著性差异＊（P＞0．05）,水钠,钾,钙含量也无显著性差异（P＞0．05）,然而,其钾,镁含量显著增高（P＜0．01）,脊髓组织变性坏死程度重于C1组,但较B组为轻,结论：早期应用醒髓汤能够有效地抑制继发性脊髓损伤。     

脊髓损伤后脊髓自由基和超氧化物岐化酶的动态变化

目的：研究脊髓损伤后脊髓内自由基丙二醛(MDA)含量及超氧化物岐化酶(SOD)的活性变化，以探讨自由基在脊髓继发性损伤中的作用机制。方法：42只健康家兔采用改良式Allen氏法造成脊髓损伤模型，测定其损伤后12h、48h、3d、7d、14d及21d脊髓组织内自由基含量和超氧化物岐化酶的活性。结果：脊髓损伤后，MDA在24h内显著升高，7d达最高峰，升幅达90％，并随之逐渐下降；伤后SOD活性显著下降，3d时达最低，降幅达54％，随后并逐渐回升。结论：自由基和超氧化物歧化酶参与了脊髓继发性损伤的病理过程。     

甲泼尼龙对急性脊髓爆震伤后脊髓继发性损伤的影响

目的探讨甲泼尼龙（MP）对脊髓爆震性损伤早期救治的效果及其机制。方法家兔36只，随机分为三组：对照组、损伤组和MP组，每组12只。除对照组外，其他两组建立局限性脊髓爆震性损伤模型，损伤组仅给予生理盐水注射，MP组致伤后立即给予MP治疗。于伤后6、12、24h取血液标本和损伤段脊髓标本，测定血液和脊髓组织中SOD、MDA和Ca^＋的含量变化情况，同时观察损伤段脊髓组织的病理变化。结果损伤组血液标本和脊髓组织中MDA、Ca^＋升高，SOD浓度下降，与对照组比较差异有统计学意义（P〈0．01）。与损伤组比较，MP组能明显降低脊髓爆震伤后血液标本和损伤脊髓中MDA、Ca^＋含量，防止SOD损失，差异有统计学意义（P〈0．01）。组织学观察可见损伤组伤后6h脊髓组织出现轻微坏死，24h出现不可逆性损伤，MP组脊髓组织坏死性改变较轻。结论急性脊髓爆震伤后立即应用MP冲击治疗，能够明显降低血清和脊髓组织中MDA、Ca^＋含量，提高SOD浓度，在一定程度上阻止继发性损伤的进一步发展。     

脊髓损伤后自由基变化及丹参对自由基影响的实验研究

目的　了解实验性脊髓损伤后血液和脊髓组织中自由基的变化及丹参对自由基的清除作用。方法　选用家兔 3 5只 ,分为正常组、损伤组、生理盐水对照组、丹参治疗组 A和 B等 5组 ,后 4组按 Allen氏法致伤造成脊髓损伤模型 ,后 3组术后分别立即静脉注射生理盐水 ,不同浓度丹参注射液。 2小时后取血液和脊髓组织测丙二醛 ( MDA)和超氧化物歧化酶 ( SOD) ,并观察脊髓病理变化。结果　脊髓损伤后血液和脊髓组织中 MDA升高 ,SOD下降 ,使用丹参后可使 MDA降低 ,SOD升高。结论　脊髓损伤后血液和脊髓组织中自由基含量升高 ,丹参能够有效清除自由基 ,两个丹参治疗组之间的抗自由基作用无显著性差异。     

三七总皂甙对脊髓损伤早期保护作用的实验研究

采用７２只成年健康杂种猫，随机分为正常、对照和治疗３组，Ａｌｌｅｎ法４００ｇｃｆ制作猫急性脊髓损伤模型，观察了三七总皂甙对脊髓损伤后早期６ｈ的治疗保护作用。结果表明，治疗组与对照组比较，脊髓损伤区血流量明显增加，脂质过氧化产物丙二醛含量、水含量及离子含量的异常改变得到改善，节段性脊髓诱发电位回复较好，光、电镜检查发现治疗组脊髓损伤后伤区组织损害程度明显减轻，提示三七总皂甙对脊髓损伤早期的继发性损害具有一定的保护作用。     

内皮素受体拮抗剂对损伤脊髓早期保护作用

目的评价非选择性内皮素(ET)受体拮抗剂PD145065对损伤脊髓的保护作用,证实ET参与脊髓损伤(SCI)后继发损伤的假设并探讨其作用机制。方法压迫法致伤大鼠脊髓(50g,1min)。损伤前10min鞘内注射PD145065或生理盐水,观察脊髓血流(SCBF)、丙二醛(MDA)、细胞内钙(［Ca2+］i)、伊文思兰(EB)及水含量变化。结果伤区SCBF在伤后5min即有明显下降,为基线的(75.23±9.21)%,2h降为(57.06±7.35)%;伤区邻近血流下降较慢,伤后30min降为(79.82±7.98)%。伤区及邻近区伤后4h?SCBF都未恢复。伤段脊髓组织中MDA、［Ca2+］i、EB和水含量均高于假手术组(P＜0.05)。PD145065明显改善了伤区SCBF,消除了伤区邻近段SCBF的下降。PD145065预处理组脊髓中MDA、［Ca2+］i、EB和水含量均低于生理盐水组(P＜0.05)。结论PD145065对损伤脊髓早期有明显保护作用,ET及其受体可能通过多种途径参与SCI后的继发损伤。临床应用ET受体拮抗剂对SCI可能有治疗作用。     

大鼠脊髓损伤后线粒体代谢功能和还原型谷胱甘肽水平的变化

目的 探讨大鼠脊髓损伤后伤段脊髓线粒体代谢功能和还原型谷胱甘肽(GSH)水平的变化.方法 取48只SD大鼠,随机分为假手术组(对照组)和脊髓损伤组(SCI组),每组又分为处理后6、12、24 h 3个时相组,每个时相组8只,分别提取伤段脊髓的线粒体,测定线粒体呼吸功能[呼吸Ⅲ态(R3)、呼吸Ⅳ态(R4)、呼吸控制率(RCR)及磷氧比(P/O)值]、三磷酸腺苷酶(ATPase)活性(Na+、K+-ATP酶和Ca2+、Mg2+-ATP酶活性)及GSH的变化.结果 SCI组在伤后6、12、24 h伤段脊髓线粒体的R3、RCR及P/O均显著低于对照组,R4显著高于对照组,差异有统计学意义(P＜0.05).SCl组Na+、K+-ATP酶和Ca2+、Mg2+-ATP酶较对照组明显降低,伤后6 h急剧下降,12 h后稍有代偿性升高,24 h后又下降,与对照组比较差异有统计学意义(P＜0.05).GSH水平SCI组与对照组相比明显降低,以伤后12 h最为明显,差异有统计学意义(P＜0.05).结论 脊髓损伤后伤段脊髓线粒体的呼吸功能、ATPase酶活性及GSH水平明显下降,说明脊髓损伤后线粒体能量代谢功能和自由基清除能力均受到明显损害.     

NGF、BDNF基因修饰嗅鞘细胞脊髓内移植对损伤脊髓细胞的保护作用

目的：观察神经生长因子(nerve growth factor，NGF)和脑源性神经营养因子(brain-derived neurotmphic fac-tor，BDNF)基因修饰的嗅神经鞘细胞(Olfactory ensheathing cells，OECs)移植对损伤脊髓组织的保护作用。方法：将脊髓半横断伤SD大鼠模型，随机分为：NGF、BDNF基因修饰的OECs移植组(A组)、OECs移植组(B组)、损伤对照组(C组)和正常对照组(D组)。24h后每组8只动物取伤段标本，测水离子含量。其余动物第6周和12周每组8只动物爬坡试验，评价下肢运动功能及运动诱发电位(MEP)检测。结果：脊髓损伤(SCI)后组织水肿，Na^ 、Ca^2 离子浓度升高，K^ 、Mg^2 离子浓度降低。NGF、BDNF、基因修饰的OECs脊髓内移植后显著改善这些变化，且使SCI后神经功能有显著恢复。结论：NGF、BDNF基因修饰的OECs脊髓内移植对SCI有保护作用。其机制可能与减少神经细胞离子失衡，改善细胞内环境有关。     

兔脊髓损伤后脑红蛋白的表达变化及其意义

[目的]探讨兔脊髓损伤(SCI)后脑红蛋白(Ngb)的表达变化规律及其意义。[方法]健康新西兰大白兔48只,随机分为8组,采用球囊压迫SCI模型,应用实时荧光定量PCR(Real-time PCR)和蛋白质印迹(West-ern blot)检测伤段脊髓组织Ngb mRNA和蛋白的表达变化情况。[结果]Ngb在正常兔脊髓组织内表达,SCI后6 hNgb表达逐渐增强,伤后24 h达到高峰;随后逐渐下降但维持较高水平至损伤后72 h,伤后7 d Ngb表达接近正常水平。[结论]Ngb存在于正常的脊髓组织内,Ngb的高表达与SCI的时间密切相关,SCI后Ngb表达上调是机体内源性保护机制之一。     

Spinal cord sodium, potassium, calcium, and water concentration changes in rats after graded contusion injury

Spinal cord Na, K, Ca, and H2O changes were measured 6 h after graded contusion injuries in 40 Sprague-Dawley rats. A 10 g weight was dropped 1.25 cm (n = 6), 2.5 cm (n = 7), 5.0 cm (n = 6), or 7.5 cm (n = 7) onto the thoracic spinal cord of 26 rats. An additional 10 rats served as laminectomy controls and 4 rats were unoperated controls. At 6 h after surgery or injury, the spinal cords were rapidly cut into 4 mm segments, weighed to obtain tissue wet weights (W), dried for 14-16 h at 97 degrees C in a vacuum oven (30 mmHg), and reweighed for tissue dry weights (D). Water concentrations ([H2O]d) were estimated from (W-D)/D in units of ml/g D. Ionic concentrations ([Na]d, [K]d, and [Ca]d) of the tissue samples were measured by atomic absorption spectroscopy with units of mumol/g D. Ionic shifts (delta [Na]d, delta [K]d, delta [Ca]d) were calculated by subtracting laminectomy control values from those measured in injured cords. Laminectomy alone significantly increased [Na]d and [H2O]d compared to unoperated controls. Mean +/- standard deviations of [H2O]d, [Na]d, [K]d, and [Ca]d were, respectively, 1.95 +/- 0.07, 182.6 +/- 5.9, 277.2 +/- 11.8, and 12.1 +/- 1.4 in unoperated controls; 2.12 +/- 0.08, 238.6 +/- 9.2, 277.8 +/- 9.2, and 11.7 +/- 1.1 in laminectomy controls. At the impact site, [K]d fell by 14-37% and [H2O]d rose by 14-24%, [Na]d by 13-64%, and [Ca]d by 65-137% of laminectomy control values. delta [Na]d, delta [K]d, and delta [Ca]d correlated linearly with impact velocities; [Ca]d increased by 1.0% per cm/sec (r = 0.995, p less than 0.005), [Na]d increased 0.67% per cm/sec (r = 0.950, p less than 0.01), and [K]d decreased 0.34% per cm/sec (r = 0.964, p less than 0.01). Neither delta [H2O] nor delta [Na]d + delta [K]d consistently predicted impact velocity. [Na]d + [K]d correlated with [H2O]d with a slope of 177.4 mumol/ml (r = 0.697, p less than 0.005). Since Na and K constitute greater than 95% of tissue inorganic ions, the slope approximates net ionic shift per ml of water entry or the ionic osmolarity of edema fluid. These results indicate that increasing contusions produce graded ionic shifts and that edema does not predict contusion severity. These data support our hypothesis that net ionic shifts cause edema in injured spinal cords.     

Cerebrospinal fluid lactate and electrolyte levels following experimental spinal cord injury.

Cerebrospinal fluid (CSF) lactate, sodium (Na+), potassium (K+), calcium (Ca++), magnesium (Mg++), and chloride (C1-) levels were determined for 17 to 21 days following experimental spinal cord compression in cats. Laminectomies were performed at L-2 under general anesthesia with aseptic techniques. Paraplegia was produced by applying a 170-gm weight transdurally for 5 minutes. Significant increases in CSF lactate levels were observed on the first through ninth days post injury with peak levels (50% above normal) occurring at Day 5. The only significant postinjury CSF electrolyte changes were elevation in Ca++ concentration on Days 3, 9, 11, 13, and 15, elevation in K+ concentration on Days 9 and 11 and decline in C1- levels on the first day. The CSF K+ increase probably reflected cellular loss of K+ from damaged tissue whereas the Ca++ rise may have resulted from increased CSF protein levels. The prolonged elevation of CSF lactate indicates that tissue hypoxia plays a role in spinal cord compression paralysis, and that there is a continuing hypoxia of metabolically active spinal cord tissue for several days post injury.     

Changes of free iron contents and its correlation with lipid peroxidation after experimental spinal cord injury

Objective: To observe the dynamic changes of free iron contents and its relationship to the changes of lipid peroxidation after experimental spinal cord injury (SCI). Methods: Sprague Dawley rats were randomly divided into three groups: Group A (n=6) received no operation; Group B (n=48) received only laminectomy (sham) ; and Group C (n=48) received both laminectomy and traumatic injury ( SCI model). The SCI animal models were made by using an modified Alien‘s weight-drop device (50 g. cm) on T12. Rats were sacrificed at 0.5, 1, 3, 6, 12, 24 hours after injury. The levels of free iron involved in spinal cord segments at different time points were measured by blcomycin assay. The malondialdehyde (MDA) was also measured by the thiobarbituric acid (TBA). Results: After SCI in Group C, the level of free iron showed a significant increase at 0.5 hour compared to Groups B and A, restored to the control level at 6 h; the level of MDA was increased at 0.5 hour, peaked at 3 hours, returned to the control level at 12 hours; the concentrations of free iron and lipid peroxidation in injured rats were significantly and positively correlated at 0.5-3 hours. Conclusions: After SCI the levels of free iron are increased quickly and might be a major contributor to lipid peroxidation in injured spinal cord.     

Effect of Mg2SO4 usage on spinal cord ischemia-reperfusion injury: electron microscopic and functional evaluation

OBJECTIVES: To evaluate the effects of intravenous magnesium sulfate (Mg(2)SO(4)) administration on ischemia-reperfusion injury of the spinal cord. MATERIAL AND METHODS: Sixteen rabbits were randomly assigned to the control (group I, 8 rabbits) and the study group (group II, 8 rabbits). The abdominal aorta was clamped for a period of 30 min followed by a reperfusion period of 60 min. The animals in group II received 0.25 ml/kg/h Mg(2)SO(4) intravenous infusion (15% Mg(2)SO(4)) throughout this procedure. The animals were then observed for 24 h after which their neurological states were evaluated and tissue samples obtained from the spinal cord were examined with electron microscopy. RESULTS: Aortic pressure distal to the cross-clamp during the occlusion period was 9 +/- 3 mm Hg in group I and 19 +/- 6 mm Hg in group II. All animals in group I were paraplegic at the end of the study. In group II the neurological outcome of 1 animal was poor while the other 7 animals were neurologically in a good condition. Electron microscopic examinations of the spinal cord tissues of group I revealed severe injury but the ultrastructure was well preserved in group II. CONCLUSIONS: Intravenous Mg(2)SO(4) administration may have protective effects on the ischemia-reperfusion injury of the spinal cord. We propose that Mg(2)SO(4) may be an additional protective pharmacological agent in thoracal and thoracoabdominal aortic surgery.     

Effects of magnesium sulfate on traumatic brain edema in rats

svarietyofneuroprotectiveagentshavebeensynthesized .However ,besidessomeagentspresentlybeingevaluatedinclinicaltrails ,mostofthesecompoundshavelimitedclinicalusebecauseofneurotoxicityandbehavioralsideeffects .Recently ,severalstudiesdemonstratedthattraumaticinjurytothebraincausesadecreaseinmagnesiumconcentrationcorrelatedwithinjuryseverity .1Sincethen ,moreandmoreattentionhasbeen paidtoMgSO4 foritsneuroprotectiveeffects .Magnesiumsulfatehasbeenwidelyusedinclinicalpracticeforalmost 10 0 years.…