兔颈脊髓半侧挫伤模型的建立及其MRI和组织学表现的研究

目的 建立兔颈脊髓半侧挫伤模型,观察不同程度损伤24小时后其MRI及组织学表现。方法 22只成年雄性新西兰兔,随机分为中度损伤组（n=9）、重度损伤组（n=9）和假手术组（n=4）。直径为3.0 mm的打击头由电磁伺服材料试验机驱动,对准C5脊髓左侧行高速挫伤（500 mm/s）。根据打击头的位移距离分为位移2.0 mm组（中度损伤组）和位移2.8 mm组(重度损伤组)。假手术组仅暴露C5脊髓,不进行挫伤。损伤后24小时每组随机取两例行MRI影像学检查,所有动物均取材进行组织学观察,测量横断面脊髓出血面积。 结果 中度损伤组打击力和位移分别为(2.47±0.39) N和(1.99±0.02) mm,重度损伤组打击力和位移分别为(5.16±0.82) N和(2.76±0.02) mm,中度损伤组的打击力明显小于重度损伤组（P<0.05）。MRI结果显示,中度及重度损伤组均可见C5左侧脊髓信号改变。HE染色显示脊髓左侧有明显的出血及脊髓组织结构破坏,中度损伤组损伤中心横截面出血面积（0.012±0.006）mm2明显小于重度损伤组（0.039±0.006）mm2（P<0.05）。 结论 本文建立的兔颈脊髓半侧挫伤模型能够控制挫伤位移,实现对脊髓的高速打击。不同程度的颈脊髓半侧挫伤在打击力、MRI影像学及组织学上均有不同。     

实验用脊髓腹侧损伤撞击器的设计及应用*☆

背景：目前脊髓损伤的基础研究主要依赖于动物损伤模型,每种脊髓损伤模型都有其适应范围及不足之处。 目的：设计并制造实验用大鼠脊髓腹侧损伤撞击器,并在大鼠脊髓损伤实验中验证仪器的使用效果。 方法：设计脊髓腹侧损伤撞击器的图纸,并按图纸组装成成品;应用该仪器制作SD大鼠脊髓腹侧损伤模型。随机分为3组,中度损伤组用23 V电压的打击力量,重度损伤组用25 V电压打击力量,对照组在安装撞击钩后,不实施打击。 结果与结论：重度损伤组BBB评分明显低于中度损伤组(P < 0.001)。BBB评分与脊髓残留组织呈线性相关(P < 0.001),     23 V电压力量30%的脊髓变形率可以制作中度脊髓损伤模型,25 V电压力量61%的脊髓变形率可以制作重度脊髓损伤模型。证实实验设计的脊髓腹侧损伤仪器能够制作大鼠脊髓腹侧中、重度损伤模型,损伤力量大小方便可控,脊髓形变可测。     

SD大鼠脊髓损伤后微环境的模拟实验

BACKGROUND: We built Sprague-Dawley rat models with mild, moderate, and severe spinal cord injuries to accord with the spinal cord injury types for basic empirical study, and consequently to further understand the microenvironmental change in Sprague-Dawley rats with spinal cord injury, and to provide help for clinical treatment. OBJECTIVE: To observe the changes in nerve function, pathological manifestation and motor sensory evoked potential in Allen’s models and Sprague-Dawley rats with complete spinal cord transection at different time points after spinal cord injury by simulating the microenviroment in Sprague-Dawley rats. METHODS: A total of 125 healthy adult female Sprague-Dawley rats were selected and randomly divided into group sham operation group, 100 gcf hit potential group (20 g×5 cm), 200 gcf hit potential (20 g×10 cm), 300 gcf hit potential group (20 g×15 cm), and spinal cord complete transection group with 25 rats in each group. At 1, 5, 7, 14 and 28 days after model establishment, the degree of spinal cord injury was identified by the BBB scores of motion function, motor evoked potential, and pathological section. RESULTS AND CONCLUSION: (1) Totally 24 Sprague-Dawley rats died in the experiment. The death rate and the rate of complications were highest in the spinal cord complete transection group. The BBB score of each group was decreased. The BBB scores in every group increased as time went on. There were significant differences between each surgery group and the sham operation group at corresponding time points (P < 0.05).  No significant difference was found between the 300 gcf hit potential group and the spinal cord complete transection group at corresponding time points (P > 0.05). (2) In each surgery group, the infiltration of inflammatory cells and obvious swelling of neurons were visible at 1 day after injury. Neural cells reduced with time prolonged. At 28 days after injury, a large number of astrocytes proliferated, scar and spinal cord cavity formed. Above symptoms were worse in the 300 gcf hit potential group and spinal cord complete transection group than in the 100 gcf and 200 gcf hit potential groups. (3) Significant differences in amplitude and latency were detectable between each surgery group and the sham operation group (P < 0.05). No significant difference in amplitude and latency was detected between the 300 gcf hit potential group and the spinal cord complete transection group at corresponding time points (P > 0.05). Results confirmed that hit potential of 20 g×5 cm, 20 g×10 cm and 20 g×15 cm can simulate the microenvironment of Sprague-Dawley rats with mild, moderate and severe spinal cord injury. The rate of complication was lower in modified Allen’s model of different hit potentials than in models of spinal cord complete transection, and was more accorded with basic research.       

Effects of acute and chronic midthoracic spinal cord injury on neural circuits for male sexual function. II. Descending pathways

In normal animals, microstimulation of the medullary reticular formation (MRF) has two effects on efferent neurons in the motor branch of the pudendal nerve (PudM). MRF microstimulation depresses motoneuron reflex discharges (RD) elicited by dorsal nerve of the penis (DNP) stimulation and produces long latency sympathetic fiber responses (SFR). The midthoracic spinal location of these descending MRF-PudM projections was studied electrophysiologically using a variety of acute and chronic lesions. Chronic lesions, in 27 mature male rats, included dorsal (DHx) or lateral (LHx) hemisections or moderate/severe contusions (Cx) at spinal level T(8). Behavioral data (sexual reflex latency, bladder voiding) obtained throughout the recovery period revealed a significant impairment of urogenital function for the DHx and severe Cx groups of animals. Microstimulation-induced PudM-RDs and PudM-SFRs, obtained in terminal electrophysiological experiments 30 days postinjury in the same 27 rats (urethan-anesthetized), were tested for a combined total of 1,404 bilateral MRF sites. PudM-RD was obtained for LHx and moderate Cx groups of animals but not for DHx or severe Cx groups. PudM-SFRs were obtained for LHx, DHx (although significantly weakened) and moderate Cx groups but not for those having received either an over-DHx or a severe Cx injury. PudM responses also were tested for 6 MRF sites in six intact control rats both before and after various select acute spinal cord lesions. For MRF sites producing a robust PudM-RD and PudM-SFR, acute bilateral lesions confined to the dorsolateral quadrant (DLQ) eliminated the PudM-RD but failed to eliminate PudM-SFRs. A deeper lesion encompassing additional white matter located dorsally in the ventrolateral quadrant (VLQ) was necessary to eliminate PudM-SFRs. Overall, these electrophysiological results provide evidence for descending projections conveying information between MRF and the lower thoracic/lumbosacral male urogenital circuitry within the DLQ and the dorsal-most aspect of VLQ at the midthoracic level of spinal cord. The alterations of supraspinal projections observed after chronic injury are likely of important clinical significance for functional recovery in cases of clinically incomplete spinal cord injury at midthoracic spinal cord.     

Autonomic dysreflexia in a mouse model of spinal cord injury.

Most experimental studies of spinal cord injury have centered on the rat as an experimental model. A shift toward a mouse model has occurred in recent years because of its usefulness as a genetic tool. While many studies have concentrated on motor function and the inflammatory response following spinal cord injury in the mouse, the development of autonomic dysreflexia after injury has yet to be described. Autonomic dysreflexia is a condition in which episodic hypertension develops after injuries above the mid-thoracic segment of the spinal cord. In this study 129Sv mice received a spinal cord transection at the second thoracic segment. The presence of autonomic dysreflexia was assessed 2 weeks later. Blood pressure responses to stimulation were as follows: moderate cutaneous pinch caudal to the injury (35+/-6 mm Hg), tail pinch (25+/-7 mm Hg), and a 0.3 ml balloon distension of the colon (37+/-4 mm Hg). Previous reports have suggested that small diameter primary afferent fiber sprouting after spinal cord injury may be responsible for the development of autonomic dysreflexia. In order to determine whether autonomic dysreflexia in the mouse may be caused by a similar mechanism, the size of the small diameter primary afferent arbor in spinal cord-injured and sham-operated animals was assessed by measuring the area occupied by calcitonin gene-related peptide-immunoreactive fibers. The percentage increase in the area of the small diameter primary afferent arbor in transected over sham-operated spinal cords was 46%, 45% and 80% at spinal segments thoracic T5-8, thoracic T9-12 and thoracic T13-lumbar L2 respectively.This study demonstrates the development of autonomic dysfunction in a mouse model of spinal cord injury that is associated with sprouting of calcitonin gene-related peptide fibers. These results provide strong support for the use of this mouse model of spinal cord injury in the study of autonomic dysreflexia.     

后路间接减压治疗合并中重度脊髓损伤胸腰椎爆裂骨折的指征和疗效

目的 比较直接减压与间接减压两种术式对合并中重度脊髓损伤的胸腰椎爆裂骨折患者的临床疗效.方法 回顾性分析2013年1月至2015年12月收治的46例合并中重度脊髓损伤的胸腰椎骨折患者资料,根据采用的手术方式分为2组:22例行后路椎弓根钉内固定复位、开窗减压术,即直接减压组;24例行后路椎弓根钉内固定复位术,即间接减压组...     

脊髓挫伤速度对颈脊髓原发性损伤影响的实验研究

目的　确定脊髓挫伤速度是脊髓损伤的因素,探讨不同速度的脊髓挫伤对大鼠颈脊髓原发性损伤的影响。  方法    20只成年雄性Sprague-Dawley大鼠随机分为快速组（500 mm/s,n=8）、慢速组（5 mm/s,n=8）和对照组（n=4）。用直径为4 mm的平头圆锥打击头在C5水平产生1.5 mm的挫伤位移。损伤后即行心脏固定,切取以挫伤部位为中心长约1.5 cm的脊髓组织。行连续矢状位冰冻切片。HE染色观察脊髓大体形态,计算出血量。β-APP免疫组化后观察轴索损伤程度。  结果　挫伤后观察到脊髓表面有一带状出血,且快速组出血带颜色更深。快速组挫伤位移为(1.50±0.05) mm,最大力为(5.3±1.2) N;慢速组挫伤位移为(1.51±0.04) mm,最大力为(2.8±0.6) N,两组间最大力的差异有显著性（P=0.001）。HE染色显示脊髓出血大部分都集中在灰质,白质相对较少。快速组脊髓总出血量、灰质出血量和白质出血量分别为0.94、0.71和0.23 mm3,慢速组分别为0.55、0.43和0.12 mm3,其中两组间总出血量和灰质出血量的差异有显著性（P＜0.05）。β-APP免疫组化观察到快速组轴索断裂比慢速组更为严重。  结论　脊髓挫伤速度是影响脊髓原发性损伤的因素,快速的脊髓挫伤导致的原发性脊髓损伤更为严重,导致更多的脊髓出血和轴索断裂。     

硫酸软骨素酶ABC对大鼠脊髓损伤修复的影响

为了探讨硫酸软骨素酶ABC对脊髓损伤后损伤局部瘢痕形成和脊髓传导功能修复的影响,本研究首先制作大鼠脊髓全横断损伤动物模型,并将其分为脊髓损伤组(A组)和脊髓损伤治疗组(B组)。在观察期内对动物的行为学表现进行BBB评分;用免疫荧光组织化学方法观察损伤4周后硫酸软骨素酶ABC对损伤局部的硫酸软骨素蛋白聚糖(CSPGs)的裂解作用;用辣根过氧化物酶(HRP)示踪法观察损伤8周后神经纤维的再生情况。结果显示:A组与B组之间动物的行为学评分B组优于A组,有显著性差异(P<0.01);B组动物脊髓内硫酸软骨素蛋白聚糖阳性物质的表达明显低于A组,具有显著性差异(P<0.05),而硫酸软骨素核心蛋白的表达无显著性差异(P>0.05);HRP示踪法显示B组脊髓损伤头端可见少量HRP标记的神经元胞体和纤维。本研究结果提示硫酸软骨素酶ABC能够裂解CSPGs中的葡胺聚糖链,减少瘢痕,促进损伤的神经纤维再生。     

安定对大鼠脊髓损伤的保护作用及GABAA受体拮抗剂对此作用的影响

应用大鼠脊髓挤压伤模型来研究安定对大鼠挤压伤模型脊髓损伤后的保护作用,及GABAA受体拮抗剂bicuculline对此作用的影响。实验大鼠分为对照组、安定组、安定联合bicuculline组及bicuculline组,应用大鼠脊髓挤压伤模型观察药物作用72h后各组大鼠脊髓损伤体积变化。结果显示对照组大鼠脊髓损伤体积为(18.21±1.14)mm3;安定组大鼠脊髓损伤体积为(12.11±1.61)mm3,明显小于对照组(P<0.01);安定联合bicuculline组大鼠脊髓损伤体积为(16.34±1.59)mm3,大于安定组(P<0.01),但仍小于对照组(P<0.01);bicuculline组大鼠脊髓损伤体积为(18.45±1.98)mm3;与对照组相比无明显差异(P>0.05)。结论安定可明显减轻大鼠脊髓挤压损伤后的脊髓损伤程度,而GABAA受体拮抗剂bicuculline可拮抗此作用,说明安定通过与GABAA受体结合,可提高GABA与GABAA受体的结合力,从而上调GABA的抑制作用,减少谷氨酸的兴奋性毒性作用以达到保护脊髓的作用。     

Continuous brain-derived neurotrophic factor (BDNF) infusion after methylprednisolone treatment in severe spinal cord injury

Although methylprednisolone (MP) is the standard of care in acute spinal cord injury (SCI), its functional outcome varies in clinical situation. Recent report demonstrated that MP depresses the expression of growth-promoting neurotrophic factors after acute SCI. The present study was designed to investigate whether continuous infusion of brain-derived neurotrophic factor (BDNF) after MP treatment promotes functional recovery in severe SCI. Contusion injury was produced at the T10 vertebral level of the spinal cord in adult rats. The rats received MP intravenously immediately after the injury and BDNF was infused intrathecally using an osmotic mini-pump for six weeks. Immunohistochemical methods were used to detect ED-1, Growth associated protein-43 (GAP-43), neurofilament (NF), and choline acethyl transferase (ChAT) levels. BDNF did not alter the effect of MP on hematogenous inflammatory cellular infiltration. MP treatment with BDNF infusion resulted in greater axonal survival and regeneration compared to MP treatment alone, as indicated by increases in NF and GAP-43 gene expression. Adjunctive BDNF infusion resulted in better locomotor test scores using the Basso-Beattie-Bresnahan (BBB) test. This study demonstrated that continuous infusion of BDNF after initial MP treatment improved functional recovery after severe spinal cord injury without dampening the acute effect of MP.     

脊柱损伤的多层螺旋CT表现及其发生机制

脊柱损伤是一种常见严重创伤,其治疗周期长,合并脊髓损伤者往往出现残疾且预后不良,严重影响患者身心健康,给医疗和患者家庭造成沉重负担。影响脊柱损伤治疗方案的因素主要包括患者的神经学状况、脊柱是否不稳、脊髓压迫情况等。多层螺旋CT(MDCT)单独应用于此类患者即可快速、可靠地判断脊柱损伤的类型、神经损伤的严重程度和脊柱不稳的程度等,诊断效果明显优于常规X线检查,本文对脊柱损伤的MDCT特点进行了综述。     

脐血干细胞移植及电针治疗脊髓损伤大鼠神经生长因子及神经营养因子3的表达

背景：研究表明,脐血干细胞移植对脊髓损伤的恢复起促进作用,而电针也能够通过抑制星形胶质细胞增生,来减少损伤部瘢痕形成,故推测两者结合可能在急性脊髓损伤治疗中发挥重要作用。 目的：观察人脐血干细胞局部移植联合督脉电针治疗后大鼠脊髓损伤组织神经生长因子、神经营养因子3的表达。 方法：选取雌性SD大鼠72只,随机分为对照组、损伤组、移植组、联合组。对照组单纯性背部切口后缝合,损伤组脊髓横断处(T₁₀水平)放置约1 mm×2 mm×2 mm大小、浸润生理盐水的明胶海绵;移植组及联合组在脊髓横断处放置浸润人脐血干细胞悬液的明胶海绵,联合组于造模后1 h开始给予督脉电针治疗。在相应处理7,14,28 d后应用免疫组织化学、Western Blot及实时荧光定量PCR方法检测脊髓组织神经生长因子、神经营养因子3表达量的变化。 结果与结论：脊髓损伤后,移植组与损伤组相比,联合组与移植组相比,神经生长因子、神经营养因子3在7,14,28 d表达量均增加(P < 0.05)。Western Blot、实时荧光定量PCR与免疫组化结果相一致。结果显示人脐血干细胞移植与电针联合治疗脊髓损伤具有协同作用,显著上调损伤脊髓神经生长因子、神经营养因子3的表达水平,有利于脊髓损伤后功能恢复。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

小鼠臂丛离断对脊髓运动神经元树突结构与形态退变的影响

目的 研究臂丛离断后脊髓运动神经元树突退变与时间和损伤距离的相关性。 方法 在距离椎间孔3 mm或10 mm处处离断小鼠臂丛,术后7、14、28、56 d取材,采用MAP2免疫荧光染色和体视学分析、Golgi-Cox染色和Sholl分析观测颈膨大处脊髓前角运动神经元的树突结构和形态变化;术后28 d比较距离椎间孔3 mm和10 mm臂丛离断对脊髓运动神经元树突的影响。 结果 MAP2免疫荧光显示臂丛离断导致脊髓前角内树突的密度和完整性随时间延长逐渐下降;Golgi-Cox染色和Sholl分析显示运动神经元最长树突、总树突长度、树突最大跨度、树突3级分支的数量均呈时间依赖性下降。与距离椎间孔10 mm处离断组相比,3 mm处离断引起的树突长度退变更为明显。 结论 脊髓运动神经元树突在周围神经损伤后会发生退变,随时间延长其退变程度加重,随损伤部位与脊髓的距离延长树突长度退变程度减轻。     

Effect of melatonin on the functional recovery from experimental traumatic compression of the spinal cord

Spinal cord injury is an extremely severe condition with no available effective therapies. We examined the effect of melatonin on traumatic compression of the spinal cord. Sixty male adult Wistar rats were divided into three groups: sham-operated animals and animals with 35 and 50% spinal cord compression with a polycarbonate rod spacer. Each group was divided into two subgroups, each receiving an injection of vehicle or melatonin (2.5 mg/kg, intraperitoneal) 5 min prior to and 1, 2, 3, and 4 h after injury. Functional recovery was monitored weekly by the open-field test, the Basso, Beattie and Bresnahan locomotor scale and the inclined plane test. Histological changes of the spinal cord were examined 35 days after injury. Motor scores were progressively lower as spacer size increased according to the motor scale and inclined plane test evaluation at all times of assessment. The results of the two tests were correlated. The open-field test presented similar results with a less pronounced difference between the 35 and 50% compression groups. The injured groups presented functional recovery that was more evident in the first and second weeks. Animals receiving melatonin treatment presented more pronounced functional recovery than vehicle-treated animals as measured by the motor scale or inclined plane. NADPH-d histochemistry revealed integrity of the spinal cord thoracic segment in sham-operated animals and confirmed the severity of the lesion after spinal cord narrowing. The results obtained after experimental compression of the spinal cord support the hypothesis that melatonin may be considered for use in clinical practice because of its protective effect on the secondary wave of neuronal death following the primary wave after spinal cord injury.     

Therapeutic time window for methylprednisolone in spinal cord injured rat.

Recent clinical trials have reported that methylprednisolone sodium succinate administered within 8 hours improves neurological recovery in human spinal cord injury (SCI). Methylprednisolone, however, was ineffective and possibly even deleterious when given more than 8 hours after injury. This finding suggests that a therapeutic time window exists in spinal cord injury. In order to determine the doses, durations and timing of methylprednisolone treatment for optimal neuroprotection, a single or two bolus dose of methylprednisolone (30 mg/kg) was administered at 10, 30, 120, 150 and 240 min. after three graded spinal cord injury. The primary outcome measure was 24-hour spinal cord lesion volumes estimated from spinal cord Na+ and K+ shifts. A single 30 mg/kg dose of methylprednisolone at 10 min. after injury significantly reduced 24-hour lesion volumes in injured rat spinal cords. However, any other methylprednisolone treatment starting 30 min. or more after injury had no effect on 24-hour lesion volumes compared to the vehicle control group. Moreover, delayed treatment increased lesion volumes in some cases. These results suggest that the NYU SCI model has a very short therapeutic window.     

控释胶质细胞源性神经营养因子与骨髓间充质干细胞源神经元样细胞移植可减少脊髓损伤后空洞形成

背景：前期研究发现控释胶质细胞源性神经营养因子与骨髓间充质干细胞源神经元样细胞移植可以有效地促进猕猴脊髓损伤后运动功能的恢复。 目的：验证控释胶质细胞源性神经营养因子联合骨髓间充质干细胞源神经元样细胞移植对猴脊髓损伤后组织结构的保护作用是否优于单纯细胞移植。 方法：将急性重度脊髓损伤模型恒河猴分为3组,联合移植组采用控释神经营养因子+神经元样细胞联合移植,单纯细胞移植组给予神经元样细胞移植,对照组给予磷酸盐缓冲液。制备脊髓组织石蜡标本,苏木精-伊红染色后显微镜下观察空洞形成情况,并应用图像分析系统计算空洞面积。 结果与结论：对照组脊髓结构严重破坏,空洞面积大、累及范围广;单纯细胞移植组脊髓结构保存较好,有小面积空洞,偶有较大空洞形成;联合移植组脊髓结构保存最好,仅存在小面积空洞。组间两两比较差异有显著意义(P < 0.01)。提示与单纯神经元样细胞移植比较,控释胶质细胞源性神经营养因子联合骨髓间充质干细胞源性神经元样细胞移植对脊髓损伤后组织结构的保护作用更佳,可以在更大程度上减少脊髓空洞的形成可能是其作用机制之一。     

急性脊髓损伤模型大鼠与白细胞介素1受体拮抗剂的保护作用

背景：白细胞介素1受体拮抗剂对大鼠急性脊髓损伤后脊髓功能修复具有保护作用,但具体机制不明。 目的：观察白细胞介素1受体拮抗剂对大鼠急性脊髓损伤组织神经丝蛋白质200和胶质纤维酸性蛋白的影响。 方法：SD大鼠随机分成假手术组,生理盐水对照组和白细胞介素1受体拮抗剂治疗组。采用改良Allen氏打击法建立急性脊髓损伤大鼠模型。分别在建模后1,48和72 h获取损伤段8 mm脊髓标本。 结果和结论：免疫组织化学染色检测,白细胞介素1受体拮抗剂治疗组神经丝蛋白质200和胶质纤维酸性蛋白的表达较假手术组和生理盐水组高,差异有显著性意义(P < 0.05)。提示白细胞介素1受体拮抗剂可使急性脊髓损伤大鼠模型损伤段脊髓神经丝蛋白质200和胶质纤维酸性蛋白表达增加,对急性脊髓损伤发挥保护作用。     

Increased spinal c-Fos expression with noxious and non-noxious peripheral stimulation after severe spinal contusion

The effects of severe contusive spinal cord injury (SCI), at thoracic level 8 (T8), on lumbar c-Fos expression in the spinal cord was investigated. As hypothesized, chronic SCI has a significant effect on expression of c-Fos in the dorsal spinal sensory areas with noxious and innocuous peripheral stimulation of the sciatic nerve. This alteration to stimulation effects was measured using counts of c-Fos immunoreactive cells in the dorsal horn of the L5 lumbar spinal cord in injured animals at 90 days post-injury and in uninjured controls. The number of c-Fos immunoreactive cells increased in SCI rats only after noxious peripheral stimulation (electrical and chemical) suggesting a general increase in excitability in spinal pathways (central sensitization) associated with chronic SCI. These altered responses may represent a functional anatomical reorganization of spinal cord circuitry leading to increased dorsal horn c-Fos expression as a response to severe chronic contusive damage to the spinal cord sensory pathways.     

右美托咪定在大鼠脊髓缺血再灌注损伤中的 保护作用及机制研究

目的 探讨右美托咪定对大鼠脊髓缺血/再灌注损伤的保护作用及PI3K/Akt传导通路在其中的作用。方法 30只成年雄性大鼠随机分为假手术组、模型组和右美托咪定治疗组,每组10只。建立大鼠脊髓缺血/再灌注损伤模型,对再灌注损伤后6 h、12 h、24 h、48 h实验大鼠后肢运动功能进行评分,检测缺血脊髓前角组织中P-AKT的表达水平及神经元的凋亡指数。结果 右美托咪定可改善脊髓缺血/再灌注损伤后实验大鼠的后肢运动功能(P＜0.05);提高脊髓前角P-AKT的表达水平(P＜0.05),抑制缺血/再灌注损伤所致的脊髓神经元的凋亡(P＜0.05)。结论 右美托咪定对脊髓缺血/再灌注损伤有一定的保护作用,其机制可能与激活PI3K/Akt传导通路,从而抑制神经元的凋亡有关。     

过氧化物酶体增殖物激活受体γ激动剂对大鼠脊髓损伤后细胞自噬的影响

背景：过氧化物酶体增殖物激活受体γ受体激动剂具有抗炎和抑制神经凋亡保护作用,能在一定程度上保护脊髓神经元,对脊髓损伤后细胞自噬应激调控等产生影响。 目的：观察过氧化物酶体增殖物激活受体γ对大鼠脊髓损伤后细胞自噬的影响。 方法：将60只SD大鼠分为3组,正常对照组仅做椎板切除,不损伤脊髓,腹腔注射生理盐水;其余大鼠以改良Allen法制作大鼠脊髓损伤模型,过氧化物酶体增殖物激活受体γ组腹腔注射罗格列酮;脊髓损伤组不做处理。损伤后1,3,7,       14 d为时间点并取材,对脊髓损伤区分别进行免疫组织化学法检测,并以Western Blot法检测Beclin 1/Bcl-2的表达变化,同时采用BBB评分方法观察神经功能恢复情况。 结果与结论：大鼠脊髓损伤后第3~14天,过氧化物酶体增殖物激活受体γ组BBB 评分显著高于脊髓损伤组(P < 0.05)。脊髓损伤组和过氧化物酶体增殖物激活受体γ组均见自噬相关阳性细胞表达,过氧化物酶体增殖物激活受体γ组细胞自噬程度相对降低,Beclin 1表达较脊髓损伤组降低(P < 0.05),Bcl-2表达较脊髓损伤组明显增加(P < 0.05),神经功能增强(P < 0.05)。提示过氧化物酶体增殖物激活受体γ激动剂在一定程度上降低大鼠脊髓损伤后细胞自噬,对细胞凋亡产生拮抗作用,并在一定程度上可促进神经功能的恢复。关键词：过氧化物酶体增殖物激活受体γ;脊髓损伤;自噬;大鼠;神经功能 缩略语注释：PPARγ：Peroxisome proliferator activated receptor,过氧化物酶体增殖物激活受体γ doi:10.3969/j.issn.1673-8225.2012.15.026