神经节苷脂GM_1对脑外伤后脑保护作用的研究进展

神经节苷脂(Gangliosides)是一类糖鞘脂的总称,是正常细胞膜的组成成分,占细胞质膜总脂类的5%～10%,主要位于双脂层的外表面。在哺乳类动物中枢神经系统中含量尤其丰富,在大脑灰质中浓度最高。神经节苷脂分子是含亲水性和疏水性两种不同特性阴离子的涎酸,其亲水基团突出于细胞外液中,维持细胞膜电负性;亲脂基团位于脂质双分子层的外层内面,神经节苷脂的这一特点使其易于细胞外的各种信息发生相互反应,从而在膜上充当极其重要的调节细胞膜内蛋白质的功能。单唾液酸四己糖神经节苷脂GM1是神经节苷脂最具代表性的一种,外源性GM1注射到动物体…     

我国对神经节苷脂中GM1研究的新进展

大量的药理实验研究表明，单唾液酸四己糖神经节苷脂(GM1)对脑缺血、脑损伤、脑缺血再灌注损伤具有明显的保护作用，其作用机制可能是阻抑氧自由基产生过多的损害，减少脑出血的发生；减轻脑缺血对Na-K-ATPase的抑制作用，增强HSP70和TGF-β的表达；降低谷氨酸含量和明显减少细胞凋亡等。实验还证实，GM1对新生儿缺血缺氧性脑病、急性低压低氧脑损害、急性脊髓损伤、周围神经再生和修复都具有保护作用。临床主要用于急性缺血性脑卒中、原发性脑干损伤、急性脊髓损伤、外周神经损伤的治疗和研究。     

神经节苷脂GM1对谷氨酸介导的基底前脑神经元损伤的保护作用

目的 观察神经节苷脂GM1对谷氨酸造成的基底前脑神经元损伤的保护作用.方法 取出生后1 d乳鼠前脑基底神经元培养,随机分为正常对照组、模型组(谷氨酸损伤组)、神经节苷脂GM1保护组.用倒置相差显微镜进行活细胞观察,采用RT-PCR技术检测前脑基底神经元神经生长相关蛋白-43(Growth associated protein-43,GAP-43)的表达.结果 谷氨酸损伤组神经元在倒置相差显微镜下可见胞体回缩,突起消失或断裂.神经节苷脂GM1保护组的神经元绝大多数胞体饱满,突起明显,细胞间的网络联系仍清晰可见,接近于正常对照组;神经节苷脂GM1大脑基底神经节GAP-43的mRNA表达比谷氨酸损伤组高,两者比较差异有统计学意义(P＜0.05).结论 神经节苷脂GM1能保护基底神经元免受谷氨酸兴奋性毒性的损伤.     

红景天苷的神经保护作用及作用机制研究进展

动物实验结果显示红景天苷对多种原因引起的神经细胞和脑组织损伤均有保护作用,有望用于周围神经损伤以及脑缺血性和神经变性疾病（如脑梗死、老年痴呆、帕金森病、癫痫、抑郁、抽动秽语综合征、肌萎缩性侧索硬化症和糖尿病脑病等）的防治。其神经保护作用机制主要包括3个方面：（1）通过抗氧化作用,抑制NOX2/ROS/MAPKs和REDD1/mTOR/p70S6K信号通路,激活AMPK/SIRT1、RhoA-MAPK和PI3K/Akt信号通路,对抗各种损伤因子引起的氧化应激,抑制炎性细胞因子表达,防止细胞内Ca²⁺超载和半胱天冬酶-3活化,保护神经细胞和干细胞免遭凋亡性损伤;（2）抑制淀粉样前体蛋白β位裂解酶-1的表达和β-分泌酶活性,阻滞内源性伤害因子β-淀粉样肽生成;（3）通过阻滞Notch信号通路,促进BMP信号通路,上调多种神经营养因子表达,诱导间充质干细胞和神经干细胞定向分化成神经元,提高许旺细胞增殖和功能,从而加速神经修复、再生和功能恢复。     

外源性神经节苷脂GM1治疗急性脑梗死疗效观察

急性脑梗死是临床常见病,其发病率和致残率均高,对脑卒中患者采取积极有效的治疗对改善生活质量尤为重要。神经节苷脂(GM1)为含唾液酸的神经糖鞘脂,存在于细胞膜,可通过血脑屏障,减轻脑水肿,保护受伤的脑组织免受兴奋性神经毒素的损害,具有神经修复和促再生长作用,对急性脑梗死     

神经节苷脂GM1联合早期康复治疗急性脑梗死的疗效观察

目的 观察神经节苷脂GM1联合早期康复治疗急性脑梗死（ACI）的临床疗效及安全性评价.方法 符合入选标准的6～72 h内急性脑梗死患者30例,接受神经节苷脂GM1联合早期康复治疗（治疗组）,并与同期未接受神经节苷脂GM1治疗的30例急性脑梗死患者（对照组）对比研究.2组均常规使用改善脑循环＋抗血小板聚集药等,若梗死面积较大,加用脱水剂.所有患者均配合早期康复训练,即患者入院后第1天开始康复训练.根据病情选用适当训练方式,包括肢体摆放、关节活动及日常生活活动能力训练等,1次/d,每次1 h.神经节苷脂GM1治疗组在常规治疗基础上加用生理盐水250 ml＋神经节苷脂GM1100 mg,静脉滴注1 h以上,连续14 d为1个疗程.结果 治疗7、21、90 d后治疗组美国国立卫生院卒中量表评分分别为（10.9±8.6）、（8.5±4.7）、（6.1±3.3）分,对照组分别为（14.7±8.6）、（11.3±7.6）、（9.0±4.2）分,2组比较差异有统计学意义（均P＜0.01）.治疗后21、90 d治疗组的Barthel指数评分分别为（89.7±8.3）、（95.8±4.5）分,对照组分别为（72.8±10.5）、（80.8±5.7）分,2组比较差异有统计学意义（均P＜0.01）.2组均未见明显药物不良反应.结论 神经节苷脂GM1联合早期康复是一种改善急性脑梗死患者神经功能缺失和提高患者日常生活能力的有效方案.     

神经节苷脂GM1联合早期康复治疗急性脑梗死的疗效观察

Objective To evaluate the clinical efficacy and safety of monosialoganglioside(GM1 ) combined with early rehabilitation treatment of acute cerebral infarctions. Methods According to the inclusive and exclusive standards, 30 patients suffering acute cerebral infarctions between 6 hr and 72 hr were selected as a test group of GM1 combined with early rehabilitation treatment on acute cerebral infarctions. At the same time, other 30 patients were also selected as a control group. Clinical efficacy was evaluated according to changes of NIHSS and Barthel scores between two groups on the 21st day and 90th day. Results There was a significant difference of NIHSS scores between the test group and the control group( P ＞ 0.05 )on the 21st day and 90th day. There was also a significant difference of Barthel scores between the test group and the control group(P ＞0.01 ). No significant adverse reaction was observed. Conclusion GM1 combined with early rehabilitation therapy is an effective method of improving the neurological function impairment of acute cerebral infarction patients.     

神经节苷脂GM1联合早期康复治疗急性脑梗死的疗效观察

Objective To evaluate the clinical efficacy and safety of monosialoganglioside(GM1 ) combined with early rehabilitation treatment of acute cerebral infarctions. Methods According to the inclusive and exclusive standards, 30 patients suffering acute cerebral infarctions between 6 hr and 72 hr were selected as a test group of GM1 combined with early rehabilitation treatment on acute cerebral infarctions. At the same time, other 30 patients were also selected as a control group. Clinical efficacy was evaluated according to changes of NIHSS and Barthel scores between two groups on the 21st day and 90th day. Results There was a significant difference of NIHSS scores between the test group and the control group( P ＞ 0.05 )on the 21st day and 90th day. There was also a significant difference of Barthel scores between the test group and the control group(P ＞0.01 ). No significant adverse reaction was observed. Conclusion GM1 combined with early rehabilitation therapy is an effective method of improving the neurological function impairment of acute cerebral infarction patients.     

NGF和神经节苷脂GM1对2,5-己二酮中毒性PC12细胞的协同保护作用

目的：研究神经生长因子（Nerve Growth Factor，NGF）和神经节苷脂GM1（Ganglioside GM1）对2，5-己二酮（2，5-HD）中毒的保护作用。方法：将细胞随机分为对照组和实验组，对照组于正常培养基生长，实验组以2，5-HD、NGF和GM，处理。采用Giemsa染色法在倒置显微镜下观察细胞形态，MTT法检测细胞存活率，流式细胞计数法检测细胞凋亡率。结果：2，5-HD处理后，细胞损伤存活率降低（P〈0．01），凋亡率上升（P〈0．01）；以NGF和GM1预处理的细胞显示出明显的抗损伤性，细胞存活率提高（P〈0．05），凋亡率下降（P〈0．05），且在联合时较单独应用效果更显著（P〈0．01）。结论：2，5-HD抑制PCI2细胞存活和增殖，诱导细损伤和凋亡。NGF和GM1对2，5-HD中毒性PC12细胞显示出协同保护作用。     

神经节苷脂GM1对新生鼠缺血缺氧后NOS表达的影响

目的：探讨神经节苷酯GM1对新生儿缺氧缺血性脑病的保护作用及可能机理。方法：通过建立新生鼠缺氧缺血性脑病动物模型，观察缺血缺氧后不同时期脑组织的病理变化和一氧化氮合酶（NOS）表达，以及GM1对其影响。结果：GM1给药组脑组织损伤明显减轻，缺血缺氧可诱导脑组织中NOS表达水平上调，GM1部分地抑制了缺血缺氧后NOS的表达水平。结论：GM1对新生儿缺氧缺血性脑损伤具有一定程度的保护作用，其作用可能是通过部分抑制NOS的表达。     

神经节苷脂治疗重度新生儿缺氧缺血性脑病疗效观察

目的：观察神经节苷脂对新生儿缺氧缺血性脑病（HIE）的治疗效果。方法：用神经节苷脂治疗重度HIE 20例,对照组20例,两组均给予三项支持、三项对症治疗。观察治疗前后血清超氧化物歧化酶（SOD）和丙二醛（MDA）的水平、脑CT的改变、NBNA评分及生后1－12月龄时精神运动发育商（DQ）以评价疗效。结果：观察组治疗后血清SOD和MDA的水平、脑CT、NBNA评分及DQ检测结果均明显优于对照组,各项指标经统计学处理两组差异有显著性意义（P＜0.05,＜0.01）。结论：应用神经节苷脂治疗重度HIE确有明显疗效。     

Characterization of the binding of cholera toxin to ganglioside GM1 immobilized onto microtitre plates

Ganglioside GM1 is the receptor for cholera toxin on cell surfaces, and the binding of cholera toxin to GM1 immobilized on microtitre plates has been reported previously by several authors as an assay for the toxin (GM1-ELISA). This assay has been examined in detail. Results were independent of the adsorption solvent for GM1 (methanol or phosphate-buffered saline), the pH of aqueous solvents (7.4-10.2) and the temperature (4-37 degrees C). High and near-maximal rates of absorbance change in the assay were found for lower concentrations of GM1 (100 ng ml(-1)) and for shorter incubation times (a few hours) than reported in the literature. A method was devised to provide a semi-quantitative estimate of the amount of GM1 bound to the plate; this was found to be in the low nanogram range. Binding of cholera toxin to the immobilized GM1 required > or =1.5 h for maximal assay results. The failure of free GM1 in solution to displace cholera toxin once bound to immobilized GM1 indicated that binding to immobilized GM1 is irreversible in the time frame of the experiment. Data from the literature support the very slow dissociation rates of the toxin-GM1 complex.     

神经节苷脂GM1对缺血缺氧后谷氨酸及其转运体神经元的作用

目的 :探讨神经节苷脂GM1对新生大鼠缺氧缺血性脑病保护作用及其可能的机理。方法 :通过建立新生鼠缺氧缺血性脑病动物模型 ,应用免疫组化方法 ,观察缺血缺氧后不同时期脑组织中谷氨酸及其转运体阳性神经元的动态变化 ,以及GM1对其的影响。结果 :缺血缺氧后 6h、1、3d大脑皮层和纹状体中谷氨酸阳性神经元明显减少 ,而谷氨酸转运体阳性神经元有所增加 ,GM1组脑组织损伤明显减轻 ,谷氨酸神经元及谷氨酸转运体神经元较单纯缺氧缺血组明显增多。结论 :神经节苷脂GM1对谷氨酸神经元具有保护作用 ,可能是通过部分提高谷氨酸转运体的表达而发挥作用     

GM1 ganglioside administration partially counteracts the morphological changes associated with haloperidol treatment within the dorsal striatum of the rat

Haloperidol, a typical antipsychotic drug, causes an increase in the mean percentage of synapses within the striatum containing a discontinuous, or perforated, postsynaptic density (PSD) following 1 month of treatment (Meshul et al. 1994). This effect is not observed with the atypical antipsychotic drug, clozapine, following subchronic administration (Meshul et al. 1992a). This morphological change is also associated with an increase in the density of dopamine D₂ receptors. The synapses containing the perforated PSD are asymmetrical and the nerve terminals contain the neurotransmitter, glutamate, as demonstrated by immunocytochemistry. We have also shown that subchronic treatment with haloperidol (0.5 mg/kg per day, 30 days) results in a decrease in the density of glutamate immunoreactivity within asymmetric nerve terminals associated with perforated and non-perforated PSDs (Meshul and Tan 1994). This could be due to an increase in glutamate release, perhaps due to activation of corticostriatal synapses. Agnati et al. (1983a) reported that administration of GM1 ganglioside blocks the increase in dopamine D₂ receptors following haloperidol treatment. GM1 has also been shown to attenuate the release of glutamate (Nicoletti et al. 1989). In order to determine if similar treatment with ganglioside could block the haloperidol-induced ultrastructural changes noted above, rats were coadministered GM1 (10 mg/kg per day) and haloperidol (0.5 mg/kg per day) for 30 days. We report that GM1 blocked the haloperidol-induced increase in striatal asymmetric synapses containing a perforated PSD, but had no effect on the increase in dopamine D₂ receptors or the decrease in nerve terminal glutamate immunoreactivity. GM1, either alone or co-administered with haloperidol, also caused a small, but significant, increase in the density of all asymmetric synapses within the striatum. It is possible that the effect of GM1 in attenuating the haloperidol-induced change in glutamate synapses with perforated PSDs is primarily postsynaptic, since GM1 did not block the change in density of glutamate immunoreactivity within asymmetric nerve terminals.     

GM1 ganglioside attenuates the development of vacuous chewing movements induced by long-term haloperidol treatment of rats

Tardive dyskinesia (TD) is a serious side-effect of long-term treatment with neuroleptics. To investigate if TD may be a result of neuroleptic-induced excessive stimulation of striatal glutamate receptors, the effect of the anti-excitotoxic GM1 ganglioside was studied in a rat model of TD. In an acute experiment each of four groups of rats was treated with GM1 20 mg/kg SC + saline IP, saline SC + haloperidol 1.2 mg/kg IP, GM1 SC + haloperidol IP, or saline SC + saline IP. In a subsequent long-term experiment lasting 16 weeks, each of the four groups was treated as in the acute experiment, with the exception that haloperidol was injected IM as decanoate 38 mg/kg every 4 weeks, and the controls received vehicle injections. The behaviour was videotaped and scored at intervals during both experiments, including 16 weeks after cessation of the long-term treatment. Haloperidol induced a significant increase in vacuous chewing movements (VCM) and immobility both in the acute and in the long-term experiment. Other categories of behaviour (rearing, moving, sitting) were significantly affected only in the acute experiment. GM1 did not affect any of the acute behavioural effects of haloperidol, but significantly reduced VCM in the long-term experiment. The effects on VCM of haloperidol and GM1 persisted for at least 8 weeks after cessation of the long-term treatment. These results suggest that long-lasting changes in striatal function induced by excessive glutamate receptor stimulation may be a mechanism for the development of VCM in rats and perhaps also for TD in humans.     

神经节苷脂GM1与亚低温对缺氧缺血后脑中HSP70、NPY表达的影响

目的 探讨神经节苷脂GM1与亚低温对缺氧缺血(HI)后新生大鼠脑中热休克蛋白70(HSP70)和神经肽Y(NPY)蛋白和基因表达的影响.方法 50只新生7 d SD大鼠制作HI模型,随机分为假手术(A)组、模型(B)组、神经节苷脂GM1(C)组、亚低温(D)组和神经节苷脂与亚低温联合干预(E)组,每组10只.采用免疫组织化学和逆转录聚合酶链反应(RT-PCR)方法检测大鼠脑中HSP70、NPY蛋白及基因表达.结果 A组HSP70、NPY蛋白及其mRNA表达较弱,B组HSP70蛋白及其 mRNA表达增加,NPY蛋白及其mRNA表达明显增强,各干预组HSP70蛋白和mRNA表达进一步升高,而以E组升高更明显(P＜0.05),而NPY和mRNA在各干预组中表达减弱,联合组减弱更明显(P＜0.05).结论 神经节苷脂GM1与亚低温对新生鼠缺氧缺血性脑损伤(HIBD)的保护作用可能与影响HSP70、NPY的表达有关.     

Dose-dependent effect of GM1 ganglioside during development on inhibitory avoidance behaviour in mice: influence of the period of administration

Groups of C57BL/6 mice were injected intraperitoneally with GM1 monosialoganglioside at different ages during development and subsequently tested for the retention of an inhibitory avoidance task 24 h after training. Results show improvements in inhibitory avoidance retention according to the age of the animals, the doses of GM1 used and the length of treatment. The effective doses ranged from 20 mg/kg for all age groups after 7 days treatment to 280 mg/kg for 6- and 7-week old animals after pre-trial treatment. Six- and 7-week-old mice are more sensitive to GM1 treatment than 5-week-old animals and, with decreasing lengths of treatment, increasing doses of GM1 are needed to improve the performance of the animals. These findings show that short treatment durations can be effective in improving inhibitory avoidance retention as long as the doses of GM1 administered are increased and that animals are more sensitive to the treatment when they are 6 or 7 weeks of age than when they are 5 weeks old.     

依达拉奉联合神经节苷酯治疗血管源性帕金森综合征的临床观察

目的观察依达拉奉联合单唾液酸四己糖神经节苷酯（GMl）治疗血管源性帕金森综合征的临床疗效。方法选择96例郑州人民医院收治的血管源性帕金森综合征患者,随机分为2组。两组均予美多巴、拜阿司匹林等基础治疗,对照组给予依达拉奉30mg／次、2次／d治疗,试验组在依达拉奉的基础上加用GMl80mg／次,10：／a静脉滴注,3周一疗程。观察两组患者治疗前后帕金森病综合评分量表（UP-DRS）积分改善情况。结果试验组患者精神、行为、情绪、13常活动及运动功能评分均优于对照组（P〈0．05）。而两组并发症积分差异无统计学煮义（P〉0．05）．结诊依扶村塞联合GMl治疗向管源忡帕会套综合秤且右掂杯的临床痒特