氟桂利嗪对杏仁核点燃鼠海马Bax mRNA表达的影响

目的:观察氟桂利嗪对杏仁核点燃鼠癎性发作及海马促凋亡基因Bax mRNA表达的影响。方法:建立杏仁核点燃模型,予不同剂量氟桂利嗪灌喂点燃鼠。原位杂交法检测鼠脑海马Bax mRNA表达,图像分析软件测量阳性细胞平均吸光度。结果:正常大鼠海马存在少量Bax mRNA表达阳性细胞,点燃鼠海马各区Bax mRNA表达阳性细胞数及平均吸光度增加,氟桂利嗪处理后平均吸光度下降与剂量有关。结论:氟桂利嗪具有抗癫癎效应和拮抗点燃鼠海马Bax mRNA表达的作用。     

高压氧联合氟桂利嗪治疗偏头痛疗效分析

目的探讨高压氧联合氟桂利嗪治疗偏头痛的疗效。方法将120例偏头痛患者随机分为氟桂利嗪组、高压氧组和联合治疗组,对比分析各组间的有效率和1周治愈率。结果有效率:联合组(97.5%)高于高压氧组(82.5%)和氟桂利嗪组(80.0%),差异有统计学意义(P<0.05);1周治愈率:联合组(60.0%)、高压氧组(52.5%)高于氟桂利嗪组(22.5%),差异有统计学意义(P<0.01)。结论高压氧联合氟桂利嗪是治疗偏头痛的理想方法。     

帕罗西汀联合氟桂利嗪防治更年期偏头痛的疗效观察

目的 观察帕罗西汀联合氟桂利嗪防治更年期偏头痛的疗效.方法 将120例更年期偏头痛患者随机分成两组,帕罗西汀联合氟桂利嗪为研究组,单用氟桂利嗪为对照组,观察治疗前后偏头痛发作次数、持续时间的变化,同时采用汉密尔顿抑郁量表(HAMD)和汉密尔顿焦虑量表(HAMA)进行评定.共观察8周.结果 治疗8周末,研究组每周偏头痛发作次数(0.5±0.3)比治疗前减少(1.1±0.5),差异有统计学意义(t=8.0,P<0.01);偏头痛持续时间(h/次)比治疗前短(2.7±0.7,7.6±3.1,t=11.9,P<0.01).治疗8周末,对照组发作次数也比治疗前减少,差异有统计学意义(0.7±0.3,2.7±0.7,t=8.0,P<0.01),偏头痛持续时间(h/次)比治疗前短(2.7±0.7,7.4±3.1,t=11.5,P<0.01);治疗8周末,研究组的发作次数少于对照组(t=3.7,P<0.05),两组偏头痛持续时间差异无统计学意义(t=0,P>0.05).治疗8周末研究组HAMD和 HAMA低于对照组(HAMD:5.9±1.8,8.7±2.3,t=7.3,P<0.01;HAMA:4.9±1.7,8.8±2.1,t=11.2,P<0.01).结论 帕罗西汀联合氟桂利嗪对预防更年期偏头痛发作优于单用氟桂利嗪.     

氟桂利嗪和倍他司汀治疗良性位置性眩晕及其伴随症状的临床疗效比较

目的观察氟桂利嗪与倍他司汀治疗良性位置性眩晕(BPPV)及其伴随症状的临床疗效。方法将182例BPPV的患者随机分为氟桂利嗪治疗组和倍他司汀治疗组。氟桂利嗪治疗组给予氟桂利嗪进行常规治疗,倍他司汀治疗组施以倍他司汀治疗。两组均治疗8周为1个疗程并进行随访。比较两种药物治疗眩晕及伴随症状的疗效。结果治疗8周后,氟桂利嗪治疗眩晕的疗效高于倍他司汀(χ2=4.4138,P<0.05),在治疗头痛、自主神经伴随症状方面,氟桂利嗪的疗效也均高于倍他司汀(均P<0.01),而在治疗耳鸣方面,两组疗效比较无统计学差异(χ2=3.3442,P>0.05)。结论氟桂利嗪治疗BPPV及其伴随症状具有较好的疗效。     

牛磺酸对糖尿病大鼠周围神经病变的保护作用

目的研究牛磺酸对糖尿病大鼠坐骨神经结构、功能以及神经生长因子mRNA表达的影响。方法54只雄性Wistar大鼠随机分为模型组、牛磺酸组和正常对照组,每组各18只。大鼠于禁食12h后,一次性腹腔注射1%链脲佐菌素诱导制备糖尿病大鼠模型;72h后尾静脉采血测定血糖水平,>16.7mmol/L者纳入实验。模型制备后第8周末于光学显微镜和电子显微镜下观察坐骨神经形态改变。同时行逆转录聚合酶链反应半定量分析神经生长因子mRNA含量;化学比色法检测血清丙二醛含量;采用MS302多媒体生物信号系统分别记录模型制备后第4周、8周时大鼠坐骨神经运动神经传导速度。结果(1)与模型组相比,牛磺酸对链脲佐菌素诱导的糖尿病大鼠的体质量和血糖水平无明显改善(P>0.05)。(2)与正常对照组相比,模型组和牛磺酸组大鼠在注射链脲佐菌素后第8周血清丙二醛水平明显升高(均P<0.01),但牛磺酸组低于模型组(P<0.01)。(3)与正常对照组相比,模型组大鼠坐骨神经运动神经传导速度在制模后第4周、8周明显减慢(均P<0.01);同期牛磺酸组与模型组间差异亦有显著性意义(均P<0.05)。(4)病理观察显示,模型组和牛磺酸组大鼠在注射链脲佐菌素后第8周均表现为明显的损伤反应,但牛磺酸组病变程度较轻。(5)与正常对照组相比,注射链脲佐菌素后第8周模型组大鼠神经生长因子mRNA表达水平显著下降(P<0.01),牛磺酸组表达水平高于模型组(P<0.01)。结论牛磺酸对糖尿病周围神经病变的防治作用不是直接通过降低血糖水平,而可能是通过有效清除自由基,减轻脂质过氧化,上调神经生长因子mRNA表达而改善神经损伤实现的。     

大鼠脑出血后Fas表达与神经细胞凋亡的关系及氟桂利嗪的干预作用

目的 观察大鼠脑血肿周围脑组织Fas的表达和神经细胞的凋亡,探讨氟桂利嗪能否下调血肿周围Fas的表达而减轻神经细胞凋亡.方法 采用自体股动脉血注入大鼠尾壳核建立脑出血模型,分别于术后6h、12h、24h、2d、4d 5个时间点取脑组织,应用免疫组化方法 检测血肿周围组织Fas的表达情况,TUNEL法检测血肿周围神经细胞凋亡.结果 脑出血组大鼠脑血肿周围组织Fas的表达及细胞凋亡明显高于其他组(P＜0.01),氟桂利嗪治疗组上述指标均低于脑出血组(P＜0.01),而高于假手术组(P＜0.01), Fas的表达与血肿周围神经细胞的凋亡呈正相关(r=0.953,P <0.05).结论 Fas、神经细胞凋亡参与了大鼠脑血肿周围脑组织损伤的病理生理过程;氟桂利嗪能抑制血肿周围Fas的表达,减轻神经细胞凋亡.     

养血清脑颗粒对偏头痛患者LPA、TNF水平影响的研究

目的 探讨养血清脑颗粒对偏头痛患者溶血磷脂酸(LPA)、肿瘤坏死因子(TNF)水平的影响.方法 治疗组:160例,采用盐酸氟桂利嗪胶囊加养血清脑颗粒治疗;对照组:58例,单独使用盐酸氟桂利嗪胶囊;健康组:35例.均采用酶免法及严格按试剂说明书操作,对3组受检者外周血LPA、TNF水平进行了检测.结果 治疗组偏头痛患者外周血LPA及TNF水平在用药24h前和用药2周均较健康组高(P＜0.01),用药4周基本恢复健康组水平(P＞0.05);治疗组在用药2周、4周LPA、TNF水平均较对照组低(P＜0.05).而对照组在用药的2周、4周均较健康组高(P＜0.01),P＜0.05).结论 采用盐酸氟桂利嗪胶囊加养血清脑颗粒较单独使用盐酸氟桂利嗪胶囊治疗能更显著的降低偏头痛患者外周血LPA及TNF水平,并能更快更好的缓解头痛症状.提示LPA、TNF增高在偏头痛发作期的发病中发挥一定作用,养血清脑颗粒可有效降低偏头痛发作时LPA、TNF水平和缓解头痛症状.     

丁苯酞预处理对缺血再灌注损伤后大鼠海马神经元的保护作用

目的探讨丁苯酞(NBP)预处理对脑缺血再灌注损伤后大鼠海马神经元的保护作用。方法将120只SD大鼠随机分为假手术组、缺血再灌注组、NBP低剂量预处理组(低剂量组)、NBP中剂量预处理组(中剂量组)和NBP高剂量预处理组(高剂量组),每组24只大鼠。低、中、高剂量组大鼠分别给予20 mg/kg、40 mg/kg、80 mg/kg NBP预处理。采用改良Zea Longa线栓法制备脑缺血再灌注模型。2%氯化三苯基四氮唑(TTC)染色测量梗死体积,免疫组织化学法观察5-羟色胺(5-HT)阳性细胞数,免疫印迹法检测5-HT蛋白水平。结果 NBP低剂量组、中剂量组、高剂量组脑梗死体积显著小于缺血再灌注组(均P0.05)。中剂量组与高剂量组脑梗死体积显著小于低剂量组(均P0.05)。与假手术组比较,缺血再灌注组大鼠海马中5-HT阳性细胞数及蛋白表达明显降低(均P0.01)。与缺血再灌注组比较,NBP低、中、高剂量组的5-HT阳性细胞数及蛋白表达显著增加(均P0.05)。中剂量组与高剂量组5-HT阳性细胞数及蛋白表达显著高于低剂量组(均P0.05),高剂量组与中剂量组差异无统计学意义。结论丁苯酞预处理具有脑保护作用,其机制可能为上调缺血海马半暗带区5-HT表达。     

尼莫地平联合盐酸氟桂利嗪治疗偏头痛

目的探讨尼莫地平与盐酸氟桂利嗪联用治疗偏头痛的临床疗效及安全性。方法 50例门诊治疗的偏头痛患者随机分为实验组和对照组,实验组联用尼莫地平与盐酸氟桂利嗪,对照组仅用盐酸氟桂利嗪;疗程为8周,观察短期疗效、长期疗效及不良反应。结果实验组短期疗效、长期疗效均优于对照组(P<0.05);2组不良反应均轻微且差异无统计学意义(P>0.05)。结论尼莫地平与盐酸氟桂利嗪联用治疗偏头痛疗效确切且安全性高,值得临床上进一步推广运用。     

中枢类大麻受体拮抗剂利莫那班对2型糖尿病周围神经病变疗效的实验分析

目的 观察利莫那班对大鼠糖尿病周围神经痛变的疗效,探讨其作用机制.方法 采用链尿佐菌素(STZ)腹腔注射诱导形成糖尿病周围神经病变(DPN)模型,随机分为模型对照组、利莫那班小剂量组、利莫那班大剂量组、正常对照组.糖尿病大鼠造模成功后予利莫那班干预,开始给药24周后将模型组和正常组比较痛阈、坐骨神经传导速度.用酶联免疫吸附测定法(ELISA法)分别洲定各组大鼠血清、脊髓及坐骨神经内IL-Iβ、TNF-α的浓度.结果 利莫邢班对DNP大鼠痛阈、坐骨神经传导速度(NCV)有明显改善(P＜0.05).与对照组比较.DPN模型组大鼠的lL-Iβ、TNF-α的含量显著增高(P＜0.05),利莫那班治疗24周后.与DPN模型组比较IL-lβ、TNF-α的含量显著降低(P＜0.05).结论 利莫那班对糖尿病周围神经病变有良好的疗效,可能是通过调节自身免疫功能机制发挥作用.     

改善微循环对大鼠坐骨神经损害血管内皮细胞生长因子表达及病理改变的影响

目的:探讨改善微循环对周围神经嵌压性损害血管内皮细胞生长因子(VEGF)表达和病理改变的影响。方法:分别检测坐骨神经嵌压后12、72h和7d背根神经节细胞VEGF水平与第4周神经干、神经节病理变化、脊髓病变神经元计数等,并运用正常对照组、模型组、前列地尔组和丁咯地尔组采用SPSS10.0统计软件进行方差分析统计处理。结果:嵌压后72hVEGF水平达到高峰,与正常对照组比较,其余各组均显著增加(P<0.01,P<0.05);前列地尔组和丁咯地尔组较模型组为优(P<0.01,P<0.05);嵌压后4周前列地尔组和丁咯地尔组的神经干、神经节病理变化、脊髓病变神经元计数均优于模型组(P<0.05)。结论:对于周围神经嵌压性损害,改善微循环可增加VEGF的表达并减轻其病理损害,从而对周围神经嵌压性损害的修复具有促进作用。     

TLR4基因突变对小鼠坐骨神经损伤修复的影响

目的 探讨Toll样受体4（TLR4）基因突变达对小鼠坐骨神经损伤修复的影响。方法 取10只C3H/HeJ小鼠（TLR4基因突变作为突变组,20只C3H/HeN小鼠（TLR4基因正常）随机分为假手术组（n=10）和模型组（n=10）。突变组和模型组在暴露的坐骨神经中部用止血钳夹持60 s以建立小鼠坐骨神经损伤模型,假手术组仅暴露坐骨神经而不进行夹伤。造模后4周,采用坐骨神经功能指数（SFI）评分评定坐骨神经功能,然后每组取3只小鼠行HE染色观察坐骨神经病理改变,每组取3只小鼠采用RT-PCR检测坐骨神经组织白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）mRNA表达水平,每组取4只小鼠采用免疫印迹法检测坐骨神经组织生长相关蛋白43（GAP43）、p75神经营养素受体（p75NTR）蛋白表达水平。结果 与假手术组相比,模型组SFI评分显著降低（P<0.05）,HE染色显示细胞形态异常并出现大量嗜中性粒细胞和巨噬细胞,坐骨神经组织IL-1β、IL-6、TNF-α mRNA表达水平以及GAP43、p75NTR蛋白表达水平均显著增高（P<0.05）。与模型组相比,突变组SFI评分明显增高（P<0.05）,组织结构病理改变明显改善,IL-1β、IL-6、TNF-α mRNA表达水平以及GAP43、p75NTR蛋白表达水平显著降低（P<0.05）。结论 TLR4基因突变可促进小鼠坐骨神经损伤后修复,可能与降低IL-1β、IL-6、TNF-α等炎症因子水平有关。     

Electrical stimulation impairs early functional recovery and accentuates skeletal muscle atrophy after sciatic nerve crush injury in rats

Neuromuscular recovery after peripheral nerve lesion depends on the regeneration of severed axons that re‐establish their functional connection with the denervated muscle. The aim of this study was to determine the effects of electrical stimulation (ES) on the neuromuscular recovery after nerve crush injury in rats. Electrical stimulation was carried out on the tibialis anterior (TA) muscle after sciatic nerve crush injury in a rat model. Six ES sessions were administered every other day starting from day 3 postinjury until the end of the experiment (day 14). The sciatic functional index was calculated. Muscle excitability, neural cell adhesion molecule (N‐CAM) expression, and muscle fiber cross‐sectional area (CSA) were accessed from TA muscle. Regenerated sciatic nerves were analyzed by light and confocal microscopy. Both treated (crush+ES) and untreated (crush) groups had their muscle weight and CSA decreased compared with the normal group (P < 0.05). Electrical stimulation accentuated muscle fiber atrophy more in the crush+ES than in the crush group (P < 0.05). N‐CAM expression increased in both crush and crush+ES groups compared with the normal group (P < 0.05). Regenerated nerves revealed no difference between the crush and crush+ES groups. Nevertheless, functional recovery at day 14 post‐injury was significantly lower in crush+ES group compared with the crush group. In addition, the crush+ES group had chronaxie values significantly higher on days 7 and 13 compared with the crush group, which indicates a decrease in muscle excitability in the crush+ES animals. The results of this study do not support a benefit of the tested protocol of ES during the period of motor nerve recovery following injury. Muscle Nerve, 2010     

Directly applied low intensity direct electric current enhances peripheral nerve regeneration in rats

The influence of direct electric stimulation on nerve regeneration was studied in a model of crush injury of the sciatic nerve of rats. Forty-three rats were used and distributed in four groups according to the procedure: (1) intact nerve, inactive circuit; (2) crush injury, inactive circuit; (3) intact nerve, active circuit; (4) crush injury, active circuit. The low intensity continuous current circuit (1 microA) was implanted in the lumbar region, the anode being fixed to the muscles proximally and the cathode below the nerve distally to the lesion site. The Sciatic Functional Index (SFI) was evaluated at weekly intervals for 3 weeks, the sciatic nerve being resected on the 21st day for histologic and morphometric studies. The SFI progressively improved and the average fiber nerve density recovered to a nearly normal value in Group 2 and increased in Group 4 compared with the control groups (1 and 3), but this was accompanied by a decreased average fiber nerve diameter. Both number and diameter of inter and intra-fascicular blood vessels increased in the stimulated nerves. We conclude that low intensity direct electric stimulation enhances nerve regeneration following a controlled nerve crush injury and increases blood supply by increasing number and diameter of vasa nervorum.     

Intraoperative single administration of neutrophil peptide 1 accelerates the early functional recovery of peripheral nerves after crush injury

Neutrophil peptide 1 belongs to a family of peptides involved in innate immunity. Continuous intramuscular injection of neutrophil peptide 1 can promote the regeneration of peripheral nerves, but clinical application in this manner is not convenient. To this end, the effects of a single intraoperative administration of neutrophil peptide 1 on peripheral nerve regeneration were experimentally observed. A rat model of sciatic nerve crush injury was established using the clamp method. After model establishment, a normal saline group and a neutrophil peptide 1 group were injected with a single dose of normal saline or 10 μg/mL neutrophil peptide 1, respectively. A sham group, without sciatic nerve crush was also prepared as a control. Sciatic nerve function tests, neuroelectrophysiological tests, and hematoxylin-eosin staining showed that the nerve conduction velocity, sciatic functional index, and tibialis anterior muscle fiber cross-sectional area were better in the neutrophil peptide 1 group than in the normal saline group at 4 weeks after surgery. At 4 and 8 weeks after surgery, there were no differences in the wet weight of the tibialis anterior muscle between the neutrophil peptide 1 and saline groups. Histological staining of the sciatic nerve showed no significant differences in the number of myelinated nerve fibers or the axon cross-sectional area between the neutrophil peptide 1 and normal saline groups. The above data confirmed that a single dose of neutrophil peptide 1 during surgery can promote the recovery of neurological function 4 weeks after sciatic nerve injury. All the experiments were approved by the Medical Ethics Committee of Peking University People's Hospital, China(approval No. 2015-50) on December 9, 2015.     

Two-dimensional digital video ankle motion analysis for assessment of function in the rat sciatic nerve model

Ankle motion analysis may provide a better method to assess function in the rat sciatic nerve model than the standard method, the sciatic functional index (SFI), but it is not widely used in experiments on nerve regeneration possibly because of complicated analysis. In this study, we investigated the practical use of a two-dimensional (2D) digital video motion analysis system. Reproducibility was investigated in normal rats. Recovery of ankle motion was analyzed after sciatic, tibial, and peroneal nerve crush injury. Results were compared with scores for the SFI. Results were not significantly different from animal-to-animal and day-to-day. Interobserver variability also was small. In the analysis of recovery after separate nerve crush injuries, subtle differences in ankle plantar flexion and dorsiflexion could be detected. The method was also more sensitive than the SFI: whereas scores for the SFI had returned to normal 4 weeks after sciatic nerve crush injury, the ankle angle at mid-stance was still significantly different from that in sham-operated animals 6 weeks after the injury. 2D digital video ankle motion analysis is a practical and sensitive method to assess function in the rat sciatic nerve model.     

Effect of pulsed magnetic field on regenerating rat sciatic nerve: An in-vitro electrophysiologic study

Some experimental studies report that low-frequency pulsed electromagnetic field (PEMF) stimulation may accelerate regeneration in peripheral nerves. In the present study, effects of PEMF on the regeneration of the crushed rat sciatic nerves were investigated with histological and in-vitro electrophysiological methods (sucrose-gap). After crush injury of the sciatic nerves, rats were divided into 5, 15, 25, 38 day-groups and exposed to PEMF (1.5 h/day, intensity; 1.5 mT, consecutive frequency; 10-10-100 Hz). In the 15th day post crush, compound action potential (CAP) amplitude was measured as 5.5 ± 1 mV (crush group) and 5.4 ± 1.2 mV (crush + PEMF group). In addition, half width of CAP extended ～ 3 fold in both groups and frequency-dependent amplitude inhibition (FDI) decreased -20% at 100 Hz. In the 38th day, amplitude of CAP, half width of CAP and FDI were measured nearly intact nerve values in both groups. In histological examinations, Wallerian degeneration was observed similar progress between both groups. The results were compared between crush and crush + PEMF groups, it was found that the effect of PEMF was not significant. The authors conclude that PEMF were ineffective on rat sciatic nerve regeneration.     

Spatiotemporal expression of inducible nitric oxide synthase and cyclooxygenase 2 in the spinal cord during early stage sciatic nerve crush injury

BACKGROUND: Previous studies have shown that inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) participate in inflammatory immune responses and neuropathic pain following peripheral nerve injury. However, few reports have addressed time-dependent expression of iNOS and COX-2 following peripheral nerve injury. OBJECTIVE: To investigate spatiotemporal expression of iNOS and COX-2 during early stage sciatic nerve crush injury.DESIGN, TIME AND SETTING: The randomized, controlled, animal experiment was performed at the Laboratory of Applied Anatomy, Department of Human Anatomy and Neurobiology, Central South University, China from September 2006 to September 2007.MATERIALS: Mouse anti-rat iNOS monoclonal antibody and goat anti-rat COX-2 monoclonal antibody (Transduction Laboratory, USA), as well as biotinylated rabbit anti-mouse lgG and biotinylated rabbit anti-goat IgG (Santa Cruz Biotechnology, USA) were used in the present study.METHODS: A total of 48 healthy, adult, Sprague Dawley rats were randomly assigned to three groups. In the model group (n = 32), crush injury to the right sciatic nerve was established using an artery clamp. The model group was further assigned to four subgroups according to survival time (6,12, 24, and 72 hours), respectively (n = 8). Sham surgery (n = 8) and normal control (n = 8) groups were also established.MAIN OUTCOME MEASURES: iNOS and COX-2 expression was detected in the L4-6 spinal cord with immunohistochemistry. Gray values of iNOS- and COX-2-postive cells in the anterior horn and posterior horn of spinal cord, as well as quantification of iNOS- and COX-2-positive cells in the anterior horn of spinal cord, were measured.RESULTS: iNOS and COX-2 expression gradually increased in the anterior horn and posterior horn of the spinal cord on the damaged side over time from 6 hours following sciatic nerve injury (P＜0.05) and peaked at 72 hours. Simultaneously, the number of iNOS- and COX-2-positive cells similarly increased in the anterior horn of spinal cord on the damaged side (P＜ 0.05).CONCLUSION: iNOS and COX-2 expression increased in the spinal cord during early stage sciatic nerve crush, which suggested that iNOS and COX-2 participate in occurrence and development of inflammatory immune responses following peripheral nerve injury.     

坐骨神经损伤模型大鼠神经传导速度及损伤运动神经元内生长相关蛋白43表达与磁刺激干预

背景：磁刺激可促进损伤神经的修复。 目的：观察磁刺激对大鼠损伤坐骨神经神经传导速度及相应水平脊髓运动神经元内生长相关蛋白43表达的影响。 方法：将60只SD大鼠随机分为实验组(n=24)、模型组(n=24)和假手术组(n=12),用一新的长17 cm的止血钳钳夹坐骨神经至第二扣,以21.95×103 Pa维持10 s制备损伤模型。造模后24 h,实验组每天给予0.09 T的磁刺激。 结果与结论：造模后第2,4,8,12周,免疫组织化学染色显示实验组脊髓L4~5运动神经元生长相关蛋白43的表达较模型组相应时间点明显增高( P < 0. 05);造模后12周,电生理检测发现,与模型组比较,实验组再生神经传导速度加快,波幅升高,潜伏期缩短(P < 0.05)。说明磁刺激能提高损伤坐骨神经的传导速度,增加其对应脊髓节段运动神经元中生长相关蛋白43的表达,对大鼠损伤坐骨神经的修复起促进作用。