川楝素与肉毒毒素在神经肌肉接头相互作用的超微结构观察

本实验用电子显微镜观察了小鼠在不同时间给以川楝素和肉毒毒素后,膈肌神经肌肉接头超微结构的改变。给川楝素后立即或1小时后给毒素,其改变与单给川楝素小鼠的相似。主要是突触小泡明显减少,长管形泡较多,髓膜样或自噬体样结构经常可见等变化。但是,如果先给毒素,5小时或24小时后再给川楝素,则突触小泡平均密度比单给川楝素小鼠的高约90%。表明预先作用于神经肌肉接头的肉毒毒素对川楝素引起的突触小泡减少有阻碍效应。其他改变与单给川楝素的相似。     

A型肉毒素在去皱应用中常见的副反应

肉毒素，又名肉毒杆菌肉毒素A，是肉毒梭菌生长繁殖过程中产生的一种细菌外毒素，是一种神经毒素蛋白，作用于周围神经运动末梢，抑制周围运动神经突触前膜释放乙酰胆碱，引起肌肉暂时性松弛性麻痹，3～6个月后失活的神经末梢产生神经轴突芽生，重新激发神经．肌肉传导。近几年来肉毒素用于治疗面部皱纹，被证明是有效的生物制剂。     

A型肉毒毒素与综合康复治疗对痉挛型脑性瘫痪的疗效观察

目的探讨A型肉毒毒素注射配合运动疗法和神经肌肉电刺激治疗痉挛型脑瘫患儿的效果。方法 75例下肢痉挛脑瘫患儿分为两组:对照组38例采用运动疗法;研究组37例采用A型肉毒毒素注射后配合运动疗法和神经肌肉电刺激。治疗前后采用改良Ashworth评定量表(MAS)、粗大运动功能测试量表(GMFM-88)进行评定。结果治疗3个月后,两组患儿MAS评分、GMFM评分均优于治疗前(P<0.05),研究组疗效优于对照组(P<0.05)。结论 A型肉毒毒素注射配合运动疗法和神经肌肉电刺激可以快速降低肌张力,有效提高痉挛型脑瘫患儿的粗大运动功能。     

A-型肉毒素在面部除皱中的应用

随着人们生活水平的不断提高,为减轻岁月的痕迹,如何减少面部的皱纹一直是皮肤美容医师共同追求的目标。肉毒素注射除皱是其中之一,现就A-型肉毒素在面部除皱中的应用就有关文献综述如下。1肉毒毒素概念肉毒毒素(botulinum toxin)是由厌氧芽胞杆菌属中的肉毒杆菌分泌的一种毒性极强的神经毒素[1]。其中根据其血清抗原性的不同,可分为A、B、Cα、Cβ、D、E、F、和G 8个型[2],其中A型肉毒素(BT-A)因其稳定性最好、易于制备和保存而普遍用于临床。2肉毒素的作用机理肉毒毒素能从多方面作用于神经肌肉接头,阻断神经对肌肉的传导,导致肌肉…     

肉毒毒素A对大鼠肛门括约肌作用的实验研究

目的了解肉毒毒素A对肛门括约肌的作用效果,并初步探讨其作用机制。为肉毒毒素A治疗肛直肠痉挛性疾病奠定理论基础。方法取Wistar大鼠75只,随机分为3组,每组25只。分别注射肉毒毒素A、生理盐水和阿托品溶液。在注药前、后分别检测3组动物的肛周括约肌肌电图,同时行肛直肠测压。此外,作肛门括约肌的病理组织切片和苏木素-伊红(HE)染色,并在光镜下观察其组织学形态。结果治疗前3组动物间肌电图表现差异无统计学意义(P>0.05),平均电位振幅(97±36)μV,平均时限(3.8±0.9)ms。治疗后72h,肉毒素A治疗组的肌电图运动电位的平均振幅为(68±29)μV,低于阿托品组和生理盐水组;平均时限(4.6±1.2)ms,长于阿托品组和生理盐水组,差异有统计学意义(P<0.05)。肉毒毒素治疗组的肛直肠静息压、肛直肠最大自主收缩压、直肠肛门抑制反射值均低于生理盐水组和阿托品组,差异有统计学意义(P<0.05)。结论肉毒毒素A能有效降低肛门括约肌的压力,为临床治疗慢性出口梗阻型便秘疾病提供了新的方法和思路,值得进一步研究。     

A型肉毒毒素治疗带状疱疹后顽固性神经痛20例

目的观察A型肉毒毒素治疗带状疱疹后顽固性神经痛的效果。方法将40例带状疱疹后顽固性神经痛患者随机分为治疗组和对照组各20例，两组均排除其他因素引起的疼痛，均给予抗病毒、营养神经、对症治疗，治疗组给予A型肉毒毒素沿神经走向行全身多点皮下注射，每点注射0.1 mL（含2.5万U）。结果治疗第1天治疗组疼痛积分为（6.9±0.85）分，对照组疼痛积分为（7.8±0.7）分，两组比较差异无显著性;治疗第3，第7，第14和第30天,治疗组疼痛积分均较对照组明显下降，且均差异有显著性（均P＜0.05）。结论 沿神经走向皮下注射A型肉毒毒素可有效治疗带状疱疹后顽固性神经痛，改善患者的精神、食欲和睡眠状态。     

康复训练结合药物治疗儿童脑瘫的疗效观察

目的：探讨A型肉毒毒素辅助治疗儿童脑瘫的临床价值。方法：将86例双下肢痉挛脑瘫患儿随机分为两组：对照组43例,采用Vojta训练治疗;实验组43例,采用Vojta训练与肌肉注射A型肉毒毒素治疗。观察比较两组患儿的痉挛状况、运动功能及日常生活活动能力。结果：实验组治疗后的综合痉挛评分明显低于对照组（P〈0．05）,实验组治疗后的粗大运动功能D区、E区分值均明显高于对照组（P〈0．05）,实验组治疗后的日常生活活动能力评分明显高于对照组（P〈0．05）。结论：A型肉毒毒素能有效缓解脑瘫患儿的肢体肌肉痉挛,促进运动功能恢复。     

甲钴胺促进周围神经再生的实验研究

目的:研究甲钴胺对周围神经再生的影响.方法:将30只Wistar大鼠随机分成对照组(N)、模型组(M)和甲钴胺组(B),每组10只.通过钳夹损伤复制大鼠坐骨神经损伤模型,对照组、模型组给予灌胃生理盐水,甲钴胺组灌胃甲钻胺水溶液,14 d后观察神经纤维的数量和排列、神经传导速度、坐骨神经功能指数、后肢拉力、腓肠肌肌细胞横截而积和腓肠肌湿质量指数等指标.结果:模型组神经纤维稀疏,排列紊乱,神经传导速度减慢,坐骨神经功能指数、腓肠肌肌细胞横截面积、腓肠肌湿质量指数减小,健侧和患侧后肢拉力差值增加,与对照组比较差别有统计学意义(P＜0.01);甲钴胺组神经纤维的数量较多、排列较规则,神经传导速度、坐骨神经功能指数、腓肠肌肌细胞横截面积、腓肠肌湿质量指数高于模型组(P＜0.01),但低于正常组(P＜0.01),后肢拉力差值低于模型组(P＜0.01),但仍高于对照组(P＜0.01).结论:甲钻胺可以加快受损伤轴突的生长速度,延缓失神经支配肌肉的萎缩,促进周围神经损伤后的功能重建.     

腹腔注射A型肉毒毒素对大鼠肠道肥大细胞的影响

目的探讨腹腔注射A型肉毒毒素(BTA)对大鼠肠黏膜肥大细胞数量的影响。方法8周龄Wistar雄性大鼠40只随机分为A、B、C、D组,每组10只,A、B、C组分别腹腔注射含BTA4u、2u、1u的生理盐水2ml,D组为对照组,腹腔注射生理盐水2ml。4周后取大鼠回肠末段、回盲部、直肠标本行改良甲苯胺蓝染色测定肥大细胞数目。结果A、B组大鼠回肠末段、回盲部及直肠肥大细胞数量(个)[分别为(5.16±2.74)、(4.50±3.19);(3.83±1.78)、(3.33±2.50)和(7.00±2.53)、(7.50±3.29)]均明显少于D组[(11.16±4.48)、(8.50±3.04)、(13.66±4.83),各组P<0.05],而C组各部位计数与D组相比差异无统计学意义。结论腹腔注射A型肉毒毒素能够减少大鼠肠道肥大细胞数量。     

A型肉毒毒素治疗眼睑痉挛的疗效观察及护理

A型肉毒毒素能抑制周围运动神经末梢突触前膜乙酰胆碱释放 ,引起肌肉松弛性麻痹。我们应用于治疗眼睑痉挛 ,将药物注射于上下睑眼轮匝肌内 ,取得较满意的效果。本文就选择注射部位、掌握剂量、联合使用利多卡因局麻及护理方面进行总结。1　临床资料1.1　药物 :兰州生物制品研究所生产的注射用 A型肉毒毒素 ,每瓶 5 0单位或 10 0单位 ,用生理盐水 10 ml稀释后轻轻振荡 ,直至完全溶解。1.2　病例 :1999年 5月～ 2 0 0 0年 9月 ,筛选患 级、 级和 级眼睑痉挛的门诊患者 10 9例并分为两组进行注射。一组单独注射 A型肉毒毒素 41例 ,另一组 6…     

Synaptic terminal degeneration and remodeling at the rat neuromuscular junction resulting from a single exposure to acrylamide

Repetitive exposure to low doses of acrylamide results in extensive pathological changes at the neuromuscular junction (NMJ), but it remains undetermined if a single exposure to a larger dose will produce a similar neuropathological outcome. In the present study, morphometric and ultrastructural analyses of rat soleus NMJ were performed to determine early pathological effects of an intraperitoneal injection of 100 mg/kg acrylamide. Widespread nerve terminal degeneration, terminal sprouting, and endplate lengthening were evident as early as 4 days after injection. Degenerating terminal branches were swollen and exhibited enhanced argyrophilia. Ultrastructurally, the majority of terminals exhibited axolemmal abnormalities, neurofilament accumulations, and a paucity of synaptic vesicles; occasional swollen terminals lacked neurofilaments but contained increased numbers of tubulovesicular profiles. This early morphological pattern of nerve terminal changes suggests that acrylamide may disrupt both synaptic vesicle recycling and neurofilament degradation. These findings indicate that a single high dose of acrylamide triggers pathological lesions and remodeling in motor nerve terminals virtually identical to those resulting from multiple low doses.     

白血病抑制因子促进大鼠坐骨神经再生的作用研究

目的探讨白血病抑制因子(LIF)对大鼠坐骨神经损伤后再生的作用。方法 60只SD大鼠随机分成2组,每组30只。按Lundborg方法制成神经再生室动物模型,实验组套接管内注入LIF 50μL(0.5μg),对照组注入等量的生理盐水。术后4、8、12周,每组分别取10只大鼠进行坐骨神经指数、神经电生理学检测,然后取出硅胶管内的神经和同侧的腓肠肌进行神经肌肉组织学检查。结果术后4、8、12周实验组的坐骨神经指数、神经传导速度、有髓神经计数,有髓神经的髓鞘厚度、肌湿重均较对照组有显著改善(P<0.001)。结论白血病抑制因子能够促进大鼠坐骨神经的再生,且有肌营养作用。     

Electroneurophysiological studies in rats of acute dimethoate poisoning.

In order to investigate the mechanism of muscular weakness in the intermediate myasthenia syndrome (IMS) following acute organophosphate poisoning, the effect of dimethoate on the neuromuscular transmission was studied in rats by using the electrical stimulation single fiber electromyography (SSFEMG) and repetitive nerve stimulation (RNS). The results showed that there was a prolongation of mean consecutive difference (MCD) of the latencies of single fiber potential shown by SSFEMG in dimethoate intoxicated rats during the presence of muscle weakness when the stimuli were given at 10 or 20 Hz, and there was a remarkable decrement of compound muscle action potential (CMAP) of gastrocnemius muscle evoked by RNS on the sciatic nerve at 20 Hz in some rats with myasthenia. The frequency of neuromuscular transmission abnormalities detected by SSFEMG was significantly higher than those detected by RNS. This study demonstrates that the SSFEMG is a more sensitive electrophysiological method in the detection of neuromuscular transmission block occurred in rats of acute organophosphate poisoning with muscle weakness.     

黄芪参附对低位中枢神经-肌接头和骨骼肌疲劳的影响

目的:观察黄芪注射液和参附注射液对低位中枢、神经-肌接头和骨骼肌疲劳的影响。方法:记录蟾蜍坐骨神经干动作电位和腓肠肌收缩曲线,测定低位运动中枢、神经-肌接头和骨骼肌出现疲劳的时间。结果:与对照组比较,黄芪组和参附组低位中枢、神经-肌接头和骨骼肌疲劳的时间均明显延长(P<0.05);黄芪组和参附组对中枢的抗疲劳作用差异无显著性(P>0.05);而与黄芪组比较,参附组神经-肌接头和骨骼肌疲劳时间延长,差异具有显著性(P<0.05)。结论:黄芪注射液和参附注射液具有抗低位中枢、神经-肌接头和骨骼肌疲劳的作用。     

Neuronal glia interactions at the vertebrate neuromuscular junction

Emerging studies demonstrate that perisynaptic Schwann cells (PSCs), which are the glia cells juxtaposed to the motor nerve terminal, actively participate in multiple aspects of the neuromuscular junction. During development, PSCs guide and promote synaptic growth. In adult muscles, PSCs can sense nerve stimulation by increasing intracellular calcium and are also capable of modulating transmitter release. Although adult PSCs are not required for acute synaptic maintenance and function, they are indispensable for long-term synaptic maintenance. Furthermore, PSC sprouts lead nerve terminal extension during synaptic remodeling. After nerve injury, PSCs sprout profusely and PSC processes guide regenerating nerve terminals. Future challenges will be to identify the molecular mechanisms by which PSCs interact with the nerve terminal and the muscle fiber.     

Repetitive nerve stimulation and stimulation single fiber electromyography studies in rats intoxicated with single or mixed insecticides

The function of the neuromuscular transmission in rats dosed with phoxim (P), methomyl (M), fenvalerate (F), and mixtures of P+M and P+F was studied by using both the stimulation single fiber electromyography (SSFEMG) and repetitive nerve stimulations (RNS) to determine the single muscle fiber action potential and compound muscle action potential (CMAP) respectively. The results showed that the mean consecutive difference (MCD) in SSFEMG was significantly prolonged in P, P+M and P+F intoxicated rats during the presence of myasthenia, but not in rats dosed with F and M when stimuli were given at 10 Hz or 20 Hz, thus indicating a transmission blocking at the neuromuscular junction (NMJ) induced by P. The frequency of neuromuscular transmission abnormalities detected by SSFEMG was significantly higher than those detected by RNS. This study demonstrated that the neuromuscular junction (NMJ) blocking is more frequently seen in P, P+M and P+F poisoning than in M and F poisoning, and that SSFEMG is a more sensitive electrophysiological method than RNS for detecting neuromuscular transmission blockage in myasthenia rats with acute insecticides poisoning.     

Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction

Botulinum neurotoxins (BoNTs) and some animal neurotoxins (β-Bungarotoxin, β-Btx, from elapid snakes and α-Latrotoxin, α-Ltx, from black widow spiders) are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is different, leading to a largely-different duration of neuromuscular junction (NMJ) blockade. BoNTs induce a long-lasting paralysis without nerve terminal degeneration acting via proteolytic cleavage of SNARE proteins, whereas animal neurotoxins cause an acute and complete degeneration of motor axon terminals, followed by a rapid recovery. In this study, the injection of animal neurotoxins in mice muscles previously paralyzed by BoNT/A or /B accelerates the recovery of neurotransmission, as assessed by electrophysiology and morphological analysis. This result provides a proof of principle that, by causing the complete degeneration, reabsorption, and regeneration of a paralysed nerve terminal, one could favour the recovery of function of a biochemically- or genetically-altered motor axon terminal. These observations might be relevant to dying-back neuropathies, where pathological changes first occur at the neuromuscular junction and then progress proximally toward the cell body.     

Levocarnitine acetyl stimulates peripheral nerve regeneration and neuromuscular junction remodelling following sciatic nerve injury.

The effects of levocarnitine acetyl were investigated on both peripheral nerve regeneration and neuromuscular remodelling in male Sprague-Dawley rats, three months of age, following crush of their left sciatic nerve. Levocarnitine acetyl, 150 mg/kg/day in drinking water, was given from one week before to 5, 15, 20, and 60 days after nerve crush. The sciatic nerve was examined morphologically at all given times and morphometrically at 15, 20, and 60 days after the lesion. Morphology, at 5, 15, and 60 days, and morphometry, at 60 days after the nerve crush, were also performed on the neuromuscular junction in the soleus and extensor digitorum longus muscles. Five days after nerve crush, complete axonal degeneration was observed in both control and treated rats. At 15 and 20 days, recovery from injury in treated animals was better than in controls, as shown by a significantly higher increase in the number of regenerating axons. At the same times, denervated endplates were present in both groups. At 60 days, axonal regeneration restored the number of axons to normal values in all injured animals, while their size maturation was greater in treated rats than in controls. A markedly lower number of degenerating elements was found in treated animals. In the neuromuscular junctions of the soleus and extensor digitorum longus muscles, nerve terminal branch points were reduced in the lesioned rats in comparison with uninjured ones. However, morphometric analysis revealed a greater endplate complexity in treated animals in which, at 60 days after nerve crush, nerve terminal branching and sprouting index values were significantly higher than in controls. It is concluded that levocarnitine acetyl exerts a beneficial effect on nerve regeneration processes and synaptic remodelling in crush-induced neuropathies.     

Dantrolene effects on neuromuscular function in cat soleus muscle.

Dantrolene sodium (DS) was investigated for its effects on cat soleus muscle contractile properties and motor nerve terminal activity in particular. DS, 0.1-1.5 mg/kg i.v., caused a dose-dependent depression of indirectly elicited contractile strength which was more pronounced at lower frequencies of stimulation. Maximum tetanic strength at frequencies of 10-400 Hz was depressed to a lesser degree than contractile responses evoked by lower frequencies of stimulation; the twitch/tetanus contraction ratios were reduced with increasing dose, primarily because of diminished twitch. DS was without effect on motor nerve terminals as evidenced by normal post-tetanic repetition in the nerves following DS administration. Post-tetanic potentiation became relatively larger in amplitude as contractile strength was diminished. These data suggest that DS depresses neuromuscular function at a site other than the neural apparatus at the neuromuscular junction.     

Studies on drug-induced neuropathies. III. Motor nerve deficit in cats with experimental acrylamide neuropathy.

To assess motor nerve and motor nerve terminal function in acrylamide neuropathy, cats were given i.m. injections of acrylamide (15 mg/kg) daily for 10 days to induce a peripheral neuropathy. Tests of function were performed on the day of the 10th injection (day 0) and 7, 21 and 35 days thereafter. In untreated animals tetanic conditioning evoked stimulus-bound repetition (SBR) in 85% of soleus alpha-motoneurones. Following administration of acrylamide, the percent of axons elaborating SBR were: day 0 -- 79%, day 7 -- 71%, day 21 -- 31%, day 35 -- 22%. The response of soleus muscle to SBR is normally a post-tetanic potentiation (PTP) of contractile tension which is proportional to the tetanic conditioning frequency; during the development of the neuropathy, PTP in response to all tetanic frequencies progressively declined, concomitant with and as a result of the declining incidence of SBR. These data indicate that initial functional alterations in motor nerves during acrylamide neuropathy occurs at the level of the nerve terminal, preceding alterations in conduction velocities in the axons. However, the motor nerve deficit is not adequate, in either time to onset or severity, to account for the clinical manifestations of the neuropathy. The possible contribution to clinical signs of the neuropathy made by lesions to other peripheral nerves is discussed.