神经节苷脂联合苯巴比妥治疗新生儿脑病的研究

目的探讨神经节苷脂联合苯巴比妥治疗新生儿缺氧缺血性脑病的临床疗效及对新生儿神经功能的影响。方法选取2017年3月-2019年3月本院收治的缺氧缺血性脑病新生儿106例,随机分为两组,对照组应用苯巴比妥治疗,研究组应用神经节苷脂联合苯巴比妥治疗。比较临床治疗有效率、神经功能恢复效果、治疗前后NBNA评分统计。结果研究组临床治疗有效率、不同程度的时间恢复效果、治疗后NBNA评分均高于对照组(P<0.05)。结论治疗新生儿缺氧缺血性脑病治疗过程当中,神经节苷脂联合苯巴比妥的治疗效果理想,可改善新生儿神经功能。     

外源性神经节苷脂相关性吉兰—巴雷综合征的发病机制及诊治研究进展

吉兰―巴雷综合征（GBS）是一种以快速进行性四肢麻木无力为特点的急性炎性脱髓鞘性多发性多神经根神经病。随着外源性神经节苷脂在临床的广泛应用，该药引起的副作用也逐渐显现，外源性神经节苷脂相关性GBS是其最严重的并发症，临床上主要表现为轴索型GBS，以四肢弛缓性瘫痪为首发症状，表现为急性、严重且快速进展的周围神经受累，较其他轴索型GBS病情重，恢复时间长，预后差。目前发病机制尚不明确。静脉注射人免疫球蛋白是其具有循证医学证据的治疗方法，目前已取代血浆置换成为GBS首选治疗方法，推荐剂量为0.4 g/（kg·d），连续静滴5 d，大剂量激素治疗的效果还有待进一步探讨。早发现、早诊断、尽早停用外源性神经节苷脂、及时应用人血免疫球蛋白冲击治疗和康复治疗，可改善预后。     

Excitability of motor and sensory axons in multifocal motor neuropathy

ObjectiveTo assess excitability differences between motor and sensory axons of affected nerves in patients with multifocal motor neuropathy (MMN).MethodsWe performed motor and sensory excitability tests in affected median nerves of 20 MMN patients and in 20 age-matched normal subjects. CMAPs were recorded from the thenar and SNAPs from the 3rd digit. Clinical tests included assessment of muscle strength, two-point discrimination and joint position.ResultsAll MMN patients had weakness of the thenar muscle and normal sensory tests. Motor excitability testing in MMN showed an increased threshold for a 50% CMAP, increased rheobase, decreased stimulus-response slope, fanning-out of threshold electrotonus, decreased resting I/V slope, shortened refractory period, and more pronounced superexcitability. Sensory excitability testing in MMN revealed decreased accommodation half-time and S2-accommodation and less pronounced subexcitability. Mathematical modeling indicated increased Barrett-Barrett conductance for motor fibers and increase in internodal fast potassium conductance for sensory fibers.ConclusionsExcitability findings in MMN suggest myelin sheath or paranodal seal involvement in motor fibers and, possibly, paranodal detachment in sensory fibers.SignificanceExcitability properties of affected nerves in MMN differ between motor and sensory nerve fibers.     

丹参注射液联合神经节苷脂辅助治疗康复期脊髓损伤患者的临床疗效及机制

目的:探讨丹参注射液联合神经节苷脂辅助治疗康复期脊髓损伤(SCI)患者的临床疗效,挖掘其作用机制。方法:将新疆石河子大学第一附属医院收治的113例脊髓损伤患者随机分为对照组(n=25)、丹参注射液组(n=28)、神经节苷脂组(n=30)和联合组(n=30),对照组患者给予正常康复训练,神经节苷脂组在对照组基础上,给予静脉滴注神经节苷脂治疗60mg,每日1次,丹参注射液组在对照组基础上给予静脉滴注丹参注射液治疗10 m L,每日1次,联合组在对照组治疗基础上给予神经节苷脂联合丹参注射液治疗,连续治疗20 d,停药10 d。比较两组患者的治疗总有效率和不良反应发生率,同时于治疗前后,比较各炎症因子水平和运动、痛觉及触觉等神经功能康复指标评分;采用ELISA法检测各组患者治疗前后血清中炎症相关因子TNF-α、IL-8、IL-1β及氧化应激相关因子SOD、MDA、VE的表达。结果:联合组疗效最佳,总有效率为83.33%,高于对照组(60%)、丹参注射液组(75%)及神经节苷脂(66.67%);联合组患者运动、痛觉及触觉的ASIA评分均明显高于对照组、丹参注射液组及神经节苷脂组(P<0.05),且联合组肌力恢复正常时间、住院时间及可下地行走时间均明显低于其他组(P<0.05);所有入组患者治疗后血清炎症相关因子TNF-α、IL-8、IL-1β均低于治疗前,但联合组表达最低(P<0.05);丹参注射液组及联合组患者治疗后血清SOD、VE表达升高,MDA降低(P<0.05)。结论:丹参注射液与神经节苷脂联合应用有助于康复期SCI患者恢复,预防脊髓继发性损害,其作用机制可能与抗炎、抗氧化有关。     

神经节苷脂联合鼠神经生长因子对早产儿脑损伤后血清神经损伤标志物的影响

目的观察神经节苷脂联合鼠神经生长因子对早产儿脑损伤后血清神经损伤标志物的影响。方法选取我院胎龄均<37周的脑损伤患儿78例,随机分为对照组和试验组,每组39例。对照组给予胞二磷胆碱注射液0.125 g,每天1次,静脉滴注;试验组在对照组的基础上给予单唾液酸四己糖神经节苷脂钠注射液20 mg+注射用鼠神经生长因子18μg,每天1次,静脉滴注。2组患儿均治疗14 d。出生24 h内和出生14 d内收集血液标本,测定血清髓鞘碱性蛋白(MBP)、S^-100β蛋白、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和Toll样受体-4(TLR-4)水平,同时比较2组患者的临床疗效和药物不良反应发生情况。结果治疗后,试验组和对照组的总改善率分别为94.87%(37例/39例)和76.92%(30例/39例),差异有统计学意义(P<0.05)。治疗后,试验组和对照组的血清MBP分别为(2.01±0.58)和(2.46±0.67)μg·L^-1,S^-100β分别为(0.69±0.28)和(0.91±0.35)μg·L^-1,血清TNF-α分别为(2.04±1.03)和(3.15±1.26)μg·L^-1,IL-6分别为(161.78±44.18)和(257.63±51.36)ng·L^-1,TLR-4分别为(8.45±4.37)和(11.68±4.94)pg·m L^-1,意识恢复时间分别为(2.30±0.57)和(3.21±0.64)d,吸吮能力恢复时间分别为(4.17±0.42)和(5.01±0.45)d,原始反射恢复时间分别为(4.23±0.48)和(6.85±0.59)d,肌张力恢复时间分别为(4.68±0.49)和(7.04±0.53)d,差异均有统计学意义(均P<0.05)。试验组的药物不良反应主要有胃肠道反应及发热,药物不良反应发生率为10.26%(4例/39例);对照组的药物不良反应主要有胃肠道反应、躁动及发热,药物不良反应发生率为12.82%(5例/39例),差异无统计学意义(P>0.05)。结论神经节苷脂联合鼠神经生长因子对脑损伤早产儿的临床疗效确切,有利于缩短恢复时间,改善神经功能,且药物安全性高。     

Ganglioside promotes the bridging of sciatic nerve defects in cryopreserved peripheral nerve allografts

Previous studies have shown that exogenous gangliosides promote nervous system regeneration and synapse formation.In this study,10 mm sciatic nerve segments from New Zealand rabbits were thawed from cryopreservation and were used for the repair of left sciatic nerve defects through allograft bridging.Three days later,1 m L ganglioside solution(1 g/L) was subcutaneously injected into the right hind leg of rabbits.Compared with non-injected rats,muscle wet weight ratio was increased at 2–12 weeks after modeling.The quantity of myelinated fibers in regenerated sciatic nerve,myelin thickness and fiber diameter were elevated at 4–12 weeks after modeling.Sciatic nerve potential amplitude and conduction velocity were raised at 8 and 12 weeks,while conduction latencies were decreased at 12 weeks.Experimental findings indicate that ganglioside can promote the regeneration of sciatic nerve defects after repair with cryopreserved peripheral nerve allografts.     

Association of antibodies to ganglioside complexes and conduction blocks in axonal Guillain‐Barré syndrome presenting as acute motor conduction block neuropathy

A close relationship between acute motor conduction block neuropathy and antibodies against the complex of GM1 and GalNAc‐GD1a has been reported. This study investigates the hypothesis that conduction block at the early phase of axonal Guillain‐Barré syndrome (GBS) is also associated with such ganglioside complexes. Sera were obtained from seven French patients with initial evidence of isolated conduction blocks that resolved or progressed to acute motor axonal neuropathy. Serum IgG to asialo‐GM1 and gangliosides of LM1, GM1, GM1b, GD1a, GalNAc‐GD1a, GD1b, GT1a, GT1b, and GQ1b as well as their complexes were measured. Five of seven patients progressed within the first month of disease to AMAN. One patient had IgG antibodies against the complex of asialo‐GM1 and each of the other ganglioside antigens. Another patient carried IgG antibodies against GM1 complex with GM1b, GD1a, and GT1a as well as asialo‐GM1 complex with GD1a and GT1a. None had IgG antibodies against GM1/GalNAc‐GD1a complex. Six patients had IgG against single antigens GM1, GD1a, GalNAc‐GD1a, GD1b, and asialo‐GM1. In three patients, a reduced reaction against GM1/GalNAc‐GD1a complex was observed. The presence of conduction block in axonal GBS is not always associated with anti‐GM1/GalNAc‐GD1a complex antibodies.     

神经节苷脂GM1在帕金森氏病症状波动治疗中的应用

目的探讨神经节苷脂GM1治疗帕金森氏病(PD)的疗效和安全性。方法对33例长期服用左旋多巴等治疗帕金森氏病药物后出现症状波动的患者,加用神经节苷脂GM1100mg/d,静脉滴注,每日1次,疗程4周。分别在GM1治疗后2、3、4周对患者进行帕金森病统一评分量表(UPDRS)运动评分及日常生活活动能力(ADL)评分,并观察治疗期间药物的毒副作用。结果33例PD患者在GM1治疗后2、3、4周UPDRS运动评分分别为(23.5±8.9)、(22.8±8.3)和(22.5±9.1),与治疗前(36.7±10.2)比较,均有非常显著性差异(P<0.01);ADL评分分别为(21.4±10.9)、(20.3±9.5)和(20.6±10.2),与治疗前(30.5±12.1)比较,亦均有非常显著性差异(P<0.01)。但治疗2、3、4周的UPDRS运动评分或ADL评分两两比较,无显著性差异(P>0.05)。治疗期间没有观察到明显的毒副作用。结论对长期服用左旋多巴出现症状波动或疗效减退的PD患者,加用GM1治疗,能在一定程度上改善患者的运动功能和日常生活能力。     

Sphingomyelin changes in rat cerebral cortex during focal ischemia

Abstract

To better define the sphingolipid metabolism during focal brain ischemia, levels of ceramide, sphingomyelin, cerebroside and gangliosides were determined in rat cerebral cortex during focal ischemia produced by occlusion of the middle cerebral artery. Sphingomyelin began to decrease at 2 hours of ischemia and continued to decrease for 96 hours. In contrast, ceramide increased at 6 hours and increased to 4.2-fold at 96 hours after ischemia, and the fatty acid composition of ceramide was solely nonhydroxylated fatty acid similar to sphingomyelin. Hydroxylated fatty acid-linked cerebroside decreased at 6 hours of ischemia, whereas any significant decrease of nonhydroxylated fatty acid-linked cerebroside didn't occur for 96 hours of ischemia. There were no measurable changes in the levels of gangliosides. These results suggested that ceramide was produced in the cerebral cortex by the breakdown of sphingomyelin during early ischemia. [Neurol Res 1996; 18: 337-341]     

Enhanced Tumor Targeting of Doxorubicin by Ganglioside GMl-bearing Long-circulating Liposomes

Abstract

Doxorubicin (DXR) was encapsulated in long-circulating liposomes, composed of ganglioside GM1 (GM1)/distearoylphosphatidylcholine (DSPC)/cholesterol (CH) (0.13:1:1 in molar ratio) and sized to approximately 100 nm in mean diameter, with 98% entrapping efficiency by the transmembrane pH gradient method. Free DXR, DXR-DSPC/CH and DXR-GM1/DSPC/CH liposomes were injected intravenously into Colon 26 tumor-bearing Balb/c mice via the tail vein at a dose of 5.0 mg DXR/kg. DXR-GM1/DSPC/CH liposomes gave a higher blood level of the drug than did DXR-DSPC/CH liposomes or free DXR up to 24 hours after injection, and the area under the blood concentration-time curve (AUC) for DXR-GM1/DSPC/CH liposomes was 1.5 or 526 times higher than that for DXR-DSPC/CH liposomes or free DXR, respectively. DXR-GM1/DSPC/CH liposomes gave a decreased DXR concentration in the reticuloendothelial system (RES) of the liver and the spleen. Both liposomal formulations effectively reduced the DXR concentration in the heart as compared with that in the case of free DXR. At 6 hours after i.v. injection, DXR-GM1/DSPC/CH liposomes provided an approximately 3.3- or 9-fold higher peak DXR level in the tumor as compared with DXR-DSPC/CH liposomes or the free drug, respectively. These high tumor levels of DXR appear to reflect the prolonged residence time of the liposomes. The results suggest that encapsulation of DXR in GM1-bearing long-circulating liposomes will be useful for cancer chemotherapy.