单唾液酸神经节苷脂治疗老年急性缺血性脑卒中的临床研究

目的通过对单唾液酸神经节苷脂（ＧＭ１）治疗组与常规治疗组病人神经功能缺损程度的评定，阐明ＧＭ１在老年缺血性脑卒中患者急性期应用对局灶性脑缺血的损害有一定保护作用。方法采用Ｆｒｉｔｈｚ－Ｗｅｎｎｅｒ（ＦＷ）及ＢａｒｔｈｅｌＩｎｄｅｘ（ＢＩ）评分法，对病人进行神经学及日常生活能力和意识水平评分。结果ＧＭ１治疗组病人治疗后ＦＷ及ＢＩ评分均高于对照组（Ｐ＜０．０１）。结论ＧＭ１在缺血性脑卒中急性期使用提高了治愈率，降低了病人神经功能的缺损程度。     

神经节苷脂对不完全性脑缺血后齿状回NOS阳性神经元表达的影响

目的 :探讨神经节苷脂 (GM1 )对不完全性脑缺血及再灌注不同时间后海马齿状回一氧化氮合酶(NOS)的影响。方法 :用双侧颈总动脉夹闭加放血的方法制成大鼠不完性脑缺血及再灌注模型 ,以还原尼克酰胺腺嘌呤二核苷酸脱氢酶 (NDAPH- d)组织化学方法观察缺血及再灌注后海马齿状回 NOS阳性神经细胞变化及 GM1 对其的影响。结果 :海马齿状回在缺血 30 min时 NOS阳性细胞数最高 (4 3.6 7± 6 .71) ,再灌注 2 h、12 h、2 4 h、3d后逐渐下降 ,5 d时恢复正常水平。而 GM1 能防止脑缺血及再灌注后神经细胞受损和 NOS阳性神经细胞变化。结论 :GM1 对大鼠不完全性脑缺血及再灌注不同时间后海马齿状回 NOS的表达有抑制作用     

神经节苷脂对不完全性脑缺血后大脑皮层NOS阳性神经元表达的影响

目的 :探讨神经节苷脂 (GM1 )对不完全性脑缺血及再灌注不同时间后大脑皮层一氧化氮合酶 (NOS)的影响。方法 :用双侧颈总动脉夹闭加放血的方法制成大鼠不完性脑缺血及再灌注模型 ,以还原尼克酰胺腺嘌呤二核苷酸脱氢酶 (NADPH -d)组织化学方法观察缺血及再灌注后大脑皮层NOS阳性神经细胞变化及GM1 对其的影响。结果 :大脑皮层在缺血 3 0min时NOS阳性细胞数最高 ( 12 .83± 4.49) ,再灌注 2h、12h、2 4h、3d后逐渐下降 ,5天时恢复正常水平。而GM1 能防止脑缺血及再灌注后NOS阳性神经细胞变化。结论 :GM1 对大鼠不完全性脑缺血及再灌注不同时间后大脑皮层NOS的表达有抑制作用     

Effects of microencapsulated monosialoganglioside GM1 on cholinergic neurons

The preparation, physical characterization and effects of microcapsules containing the monosialoganglioside GM1 in an in vivo rat model are described herewith. Several preparations of microcapsules were obtained differing in physical and chemical properties. Human serum albumin (HSA) microcapsules with or without GM1 are spherical in shape, have a consistent particle size (8-10 microns in diameter) and are devoid of large pores. In agreement with our previous work, we now provide further evidence that GM1 can prevent shrinkage and the decrease of choline acetyltransferase activity in the nucleus basalis magnocellularis (NBM) of the rat following a unilateral cortical lesion. In the present study we examined the effect of microencapsulated GM1 in this in vivo rat model. Local application of HSA-microencapsulated GM1 (in doses comparable to those obtained by i.c.v. administration) onto the surface of the lesioned cortex prevents both the biochemical and morphological degenerative changes in the NBM of rats with unilateral devascularizing cortical lesions. The results from these studies show that microencapsulated GM1 can be applied successfully and a prolonged controlled release of this drug obtained, thus avoiding surgical implantation of a cannula.     

单唾液酸四己糖神经节苷酯治疗新生儿缺氧缺血性脑病90例

目的研究单唾液酸四己糖神经节苷酯(GM1)静滴治疗新生儿缺氧缺血性脑病(HIE)疗效。方法将90例HIE患儿随机分为观察组和对照组,每组45例,均予常规治疗,观察组加用GM1。观察和记录2组临床症状、体征恢复情况和新生儿行为神经测定(NBNA)评分。结果应用GM1治疗新生儿HIE对改善HIE所致的远期神经系统发育障碍有较好的疗效。结论在常规治疗基础上加用GM1是目前治疗中重度HIE较理想的方法。     

GM-1预处理减轻布比卡因诱导的N2a细胞凋亡

目的研究单唾液酸四己糖神经节苷脂(GM-1)预处理对布比卡因诱导N2a细胞凋亡后对c-Jun氨基末端激酶(JNK)、CCAAT/增强子结合蛋白同源蛋白(CHOP)表达的影响。方法体外培养小鼠神经母细胞瘤细胞N2a细胞株,取对数生长期N2a细胞,将细胞随机分为四组:对照组(C组),N2a细胞无任何药物处理;GM-1组(G组),N2a细胞中加入GM-15μmol/L处理24 h;布比卡因组(B组),N2a细胞中加入布比卡因900μmol/L处理36 h;GM-1预处理组(GB组),GM-15μmol/L预处理24h后,N2a细胞中加入布比卡因900μmol/L处理36 h。以倒置显微镜观察细胞形态学变化,采用TUNEL法检测细胞凋亡率,采用qRT-PCR法和Western blot法分别检测细胞内JNK和CHOP mRNA表达量及蛋白含量。结果与C组比较,B组和GB组细胞损伤形态明显加重,凋亡率明显升高,JNK和CHOP mRNA表达量及蛋白含量明显升高(P<0.05)。与B组比较,GB组细胞损伤形态明显减轻,凋亡率明显下降,JNK和CHOP mRNA表达量及蛋白含量明显降低(P<0.05)。结论GM-1预处理通过调控内质网应激凋亡途径中相关蛋白JNK和CHOP的表达,从而减少布比卡因诱导的细胞凋亡,减轻布比卡因引起的神经毒性。     

单唾液酸四己糖神经节苷脂缓释微球保护大鼠脊髓继发性损伤的实验研究

目的:探讨经蛛网膜下腔给予单唾液酸四己糖神经节苷脂(GM-1)缓释微球保护大鼠脊髓继发性损伤的增强效应及其机制。方法:188只成年SD大鼠随机分为对照组8只,模型组60只,普通GM-1组60只和GM-1微球组60只。采用Nys- trom法制备脊髓压迫损伤模型(50g×5min),术后24,72,168和336 h检测大鼠运动功能、脑脊液中GM-1含量,术后8,24,72,168和336 h检测大鼠脊髓组织内SOD活力和MDA含量,以及脊髓Caspase-3表达情况。结果:与模型组比较,GM-1微球组大鼠BBB运动功能评分高,脑脊液中GM-1含量多,脊髓组织内SOD活力强和MDA含量少,Caspase-3表达明显,具有显著统计学差异(P<0.01),亦优于GM-1组,但无统计学差异。结论:蛛网膜下腔给予GM-1缓释微球对脊髓继发性损伤的保护作用更强,主要机制涉及抗自由基损伤和抗细胞凋亡。     

Ganglioside GM1 attenuates scopolamine-induced amnesia in rats and mice

 Some experimental evidence suggests that the beneficial effects of monosialoganglioside GM1 on learning and memory could be related to an improving effect in central cholinergic function. The present study investigates the effects of GM1 on the memory impairment induced by scopolamine in rats or mice tested in passive (PA) and discriminative avoidance (DA) tasks, respectively. Wistar EPM-1 male rats and Swiss EPM-M1 male mice were treated daily IP with 50 mg/kg GM1 or saline for 7 or 14 days, respectively. Twenty-four hours after the last injection, GM1-treated animals received 1 mg/kg scopolamine (GM1-SCO) and saline-treated animals received 1 mg/kg scopolamine (SAL-SCO) or saline (SAL-SAL) IP. Twenty minutes later, the animals were submitted to PA or DA conditioning, and tests were performed 24 h later. The latency in entering the dark chamber of the PA apparatus (LD) presented by SAL-SCO rats was significantly decreased when compared to that presented by SAL-SAL animals. GM1-SCO animals showed an increased LD when compared to SAL-SCO animals and were not significantly different from SAL-SAL rats. GM1-SCO and SAL-SAL (but not SAL-SCO) mice spent significantly less time in the aversive enclosed arm of the discriminative avoidance apparatus when compared to the time spent in the non-aversive enclosed arm. The results are consistent with the interpretation that GM1 attenuates scopolamine-induced amnesia. Although not eliminating the participation of other transmitter systems, the present study indicates a possible role of central cholinergic transmission in the action of this compound on learning and memory. Received: 21 October 1997 / Final version: 8 June 1998     

GDNF和GM1体外联合诱导骨髓基质干细胞向多巴胺能神经元分化的实验研究

目的应用GDNF和GM1体外联合诱导MSCs转化为多巴胺能(DA)神经元。探索体外诱导MSCs定向分化为DA能神经元的最佳条件。方法取雄性Wistar大鼠股骨和胫骨骨髓,密度梯度离心法分离获取单个核细胞。进行MSCs的体外培养和传代扩增。采用贴壁培养法使MSCs得到纯化。依据加入的神经营养因子不同分为对照组及实验组(GM1组、GDNF组、GDNF GM1组)。诱导过程中在倒置显微镜下观察细胞形态变化,分别在诱导第3天、第7天进行NSE、GFAP、TH免疫细胞化学检测。计数NSE和TH阳性细胞数,并计算阳性细胞百分比。采用SPSS10.0软件进行统计学处理。结果对照组可见少量NSE阳性细胞。各实验组比较发现,GDNF GM1组NSE阳性细胞率最高,GDNF组次之,GM1组最低。单独应用GDNF和GM1不能诱导MSCs表达TH,联合应用GDNF和GM1可诱导MSCs表达TH。随着诱导时间的延长,TH阳性表达增加。结论GDNF能够单独诱导MSCs向神经元样细胞分化,GM1不能单独诱导MSCs分化为神经元样细胞,但与GDNF联合,不仅可明显促进MSCs向神经元样细胞分化,而且部分细胞能够表达TH。     

Monosialoganglioside GM1 blood levels in maternal and newborn umbilical cord blood at birth

Blood levels of the monosialoganglioside GM₁ (nomenclature according to Svennerholm) were tested at birth in the umbilical cord of 37 neonates and their mothers. Comparisons were made based on gestational age and modality of delivery. GM₁ blood levels at birth were significantly higher in mothers than in newborns (373.66±56.83 ng/ml vs 217.95±21.24 ng/ml; P<0.01). Newborns delivered by cesarian section showed levels of GM₁ significantly higher than those delivered vaginally (298.97±38.55 ng/ml vs 169.62±12.62 ng/ml; P<0.01). and preterm newborns had significantly higher levels of GM₁ than full-term newborns (253.50±40.83 ng/ml vs 193.71±21.74 ng/ml; P<0.01). No differences in blood levels of GM₁ were observed in the mothers in relation to length of pregnancy or modality of delivery. The higher levels of GM₁ observed in preterm newborns indicate an increased turnover and/or enhanced bioavailability of the monosialoganglioside GM₁ for the developing central nervous system. Further data are required to evaluate the significance of the increased cord levels of GM₁ in neonates after cesarian section.