三七三醇皂苷对脑缺血大鼠脑室下区细胞增殖及星形胶质细胞的影响

目的:研究三七三醇皂苷(PTS)对局灶性脑缺血再灌注后脑室下区(SVZ)细胞增殖及星形胶质细胞的影响。方法:60只雄性SD大鼠随机分为假手术、生理盐水(NS)和PTS组,每组设再灌注3、7、14、21d亚组,每个时段各5只。采用改良的线栓法制备大脑右侧中动脉阻塞2h的大鼠短暂局灶性脑缺血模型,观察5-溴脱氧尿嘧啶和胶质纤维酸性蛋白(GFAP)在SVZ的表达情况。结果:再灌注后7d,PTS组与NS组SVZ细胞增殖水平达到峰值,至再灌注21d细胞增殖水平已明显回落,但仍高于正常水平;再灌注后7、14d,PTS组SVZ细胞增殖水平显著高于NS组。再灌注后3d,PTS组与NS组SVZ细胞GFAP表达达到峰值,至再灌注14d已恢复正常水平;再灌注后3、7d,PTS组SVZ的GFAP阳性细胞数显著高于NS组。结论:PTS可促进缺血再灌注后SVZ细胞的增殖水平,并上调GFAP的表达。     

叶酸对脑梗死大鼠星形胶质细胞GFAP表达的影响

目的:探讨叶酸对脑梗死大鼠星形胶质细胞纤维酸性蛋白(GFAP)表达的影响。方法:将SD大鼠随机分为假手术(SO)组、缺血(IM)组、缺血 低剂量叶酸(IM LFA)组和缺血 高剂量叶酸(IM HFA)组。通过叶酸灌胃给药28d后制备大脑中动脉栓塞模型,采用免疫荧光双标记的方法检测各组大鼠脑缺血后脑组织GFAP的荧光强度及BrdU GFAP双标阳性细胞密度。结果:在7d及14d4组均可见BrdU GFAP双标阳性星形胶质细胞,缺血 叶酸组GFAP荧光强度及BrdU GFAP双标阳性细胞密度均高于IM组及SO组,差异均有统计学意义(P<0.05或P<0.01)。结论:补充叶酸可以使星形胶质细胞GFAP表达增强,并促进神经干细胞的分化,从而对脑梗死大鼠具有保护作用。     

星形胶质细胞的研究

近年来星形胶质细胞应用研究是神经科学研究的热点,该文综述了星形胶质细胞的形态、调节机制、功能、与疾病的联系等,星形胶质细胞在神经系统的生长及修复中起重要作用。     

三七三醇皂苷增进大鼠脑缺血耐受的作用及对GFAP和bFGF表达的影响

目的观察三七三醇皂苷(PTS)对预缺血诱导的脑缺血耐受作用及胶质纤维酸性蛋白(GFAP)、碱性成纤维细胞生长因子(bFGF)表达的影响。方法采用改进的二次线栓法制备SD大鼠缺血耐受模型,并随机分为大脑中动脉缺血(MCAO)组、预缺血组(IP MCAO)和PTS组(IP PTS MCAO),分别给予10min的假手术、预缺血或预缺血加PTS,3d后使MCAO2h,再灌注22h后处死,比较各组神经功能评分、梗死体积、病理形态学变化及GFAP和bFGF的表达。结果PTS组神经功能缺损减轻、梗死体积缩小和病理形态学改变均较预缺血组更为明显,GFAP、bFGF表达均高于其余两组(P<0.01)。结论三七三醇皂苷(PTS)具有增强预缺血诱导的脑缺血耐受作用,并上调GFAP、bFGF表达。     

严重烫伤早期脑内星形胶质细胞与GFAP表达的变化

目的:探讨星形胶质细胞形态变化及胶质原纤维酸性蛋白(GFAP)表达与严重烫伤引起的血脑屏障损伤之间的关系.方法:健康SD大鼠,随机分为正常组、烫伤组(分3、6、12、24、48 h 5个时相点),用透射电镜观察血脑屏障超微结构变化;紫外分光光度计检测脑伊文蓝(Evan's Blue,EB)含量.免疫组化观察脑GFAP表达.结果:正常组星形胶质细胞结构清楚,各种细胞器完整.烫伤后3 h线粒体肿胀,空泡化.严重烫伤后脑EB明显高于正常组(P<0.01),以6～12 h最为明显,24 h后开始下降.GFAP的阳性表达定位于星形胶质细胞的胞浆及突起内,呈棕褐色或棕黄色.GFAP阳性细胞轮廓清楚,细胞突起成星形.烫伤后GFAP阳性细胞数目明显增多,染色增强,平均光密度增高(P<0.01),12～24 h达高峰且形态不规则,48 h后开始下降.结论:严重烫伤后星形胶质细胞活化、GFAP表达增加与血脑屏障通透性增高有关,提示GFAP在严重烫伤早期对血脑屏障的损伤有重要作用.     

三七三醇皂苷对糖尿病大鼠视网膜神经节细胞的保护作用

【摘要】目的探讨三七三醇皂苷（PTS）对糖尿病大鼠视网膜神经节细胞（RGC）的保护作用及机制。方法SD大鼠随机分为对照组、糖尿病组及治疗组,糖尿病组及治疗组腹腔注射链脲佐菌素诱导糖尿病动物模型,治疗组给予PTS50mg·kg-1·d-1灌胃,1个月后免疫荧光组化双标检测Nogo受体与RGC特异性标志物Brn3a的共存情况,Western blot检测视网膜Nogo受体表达,试剂盒检测视网膜丙二醛（MDA）含量,HE染色观察RGC数量。结果Brn3a与Nogo受体于视网膜内大量共存。与对照组相比,糖尿病组视网膜Nogo受体表达上调,MDA含量增加,RGC数量减少（均P＜0.001）;与糖尿病组相比,治疗组视网膜Nogo受体表达减少,MDA含量降低,RGC数量增加（P＜0.001）。结论PTS可能通过抑制糖尿病大鼠视网膜RGC内Nogo受体的表达,抑制视网膜氧化应激,从而保护糖尿病视网膜RGC。     

蛛网膜下隙注射胶质细胞源性神经营养因子抑制脊神经结扎大鼠脊髓背角胶质原纤维酸性蛋白表达

目的观察蛛网膜下隙注射胶质细胞源性神经营养因子(GDNF)对脊神经结扎(SNL)大鼠脊髓背角胶质原纤维酸性蛋白(GFAP)的影响。方法采用结扎SD大鼠第5~第6腰脊神经(L5~L6)制备SNL模型。术后隔日一次性蛛网膜下隙注射10μl GDNF2 g·L-1组。术后第3,7和14天采用免疫组织化学和Western免疫印迹法测定脊髓背角处GFAP蛋白表达。结果免疫组化结果显示,SNL组在术后第3天、第7天和第14天脊髓GFAP阳性细胞数目明显增加,可持续至第14天,而正常对照组与假手术组的星形胶质细胞未发生此种改变。GDNF组的阳性细胞显著减少。Western印迹结果显示,正常对照组和假手术组脊髓背角均出现GFAP免疫阳性条带,灰度值较低;SNL在术后第3天即可诱导脊髓背角GFAP蛋白的表达,随着时间的延长,GFAP蛋白的灰度值逐渐升高,术后第3,7,14天分别为2.55±0.33,2.88±0.79和3.12±0.75(P<0.01)。与SNL模型组比较,GDNF可显著降低GFAP的表达水平,术后第3,7,14天分别为1.61±0.38,1.65±0.64和1.57±0.41(P<0.01)。结论蛛网膜下隙注射GDNF减轻大鼠神经病理性疼痛机制可能与其抑制脊髓背角GFAP蛋白表达有关。     

大鼠脑梗死早期星形细胞胶质化及其与神经营养因子的关系

目的 探讨星形南细胞（ＡＳ）在脑梗死早期的变化及与神经营养因子的关系。方法 运用免疫组织化学技术检测Ｍｉｄｋｉｎｅ（ＭＫ）、星形胶质纤维酸性蛋白（ＧＦＡＰ）的动态变化。结果 梗死后１天,梗死边缘开始表达ＧＦＡＦ。梗死后２天,ＧＦＡＰ表达达高峰。ＭＫ于梗死后１天表达,随后其阳性梗死后２￣４天表达逐步增强。结论 脑梗死早期星形胶质细胞增生可能与分泌神经营养因子及损伤后的修复有关。     

鸟苷酸环化酶抑制剂ODQ对星形胶质细胞cGMP及GFAP的影响

目的分析星形胶质细胞中cGMP浓度变化对GFAP表达影响,探讨NO-sGC-cGMP信号转导系统对星形胶质细胞活化机制。方法分离纯化SD乳鼠大脑皮层细胞,经原代及传代培养,随机分成8组,经ODQ干预后,放射免疫测其cGMP浓度,同时免疫荧光测GFAP荧光强度OD值,代表GFAP表达强度,统计学作相关分析。结果sGC选择性抑制剂ODQ干预后,随着cGMP浓度降低,GFAP表达量也随之降低,其相关系数为0.76(P=0.036)。结论cGMP浓度与GFAP合成呈高度正相关。结合NO-sGC-cGMP信号传导途径,该途径可能对GFAP的合成具有调节作用。     

乳黄片对高氨环境中星形胶质细胞CRL-2541活力及GFAP表达的影响

目的 探讨乳黄片脑脊液对高氨环境中星形胶质细胞活力和胶质纤维酸性蛋白（GFAP）表达的影响. 方法 运用中药脑脊液药理学方法 把体外培养的CRL-2541细胞分为空白对照组、氨损伤组、正常脑脊液（CSF）组、乳黄片脑脊液组,各组加入不同溶液. MTT检测CRL-2541活力,免疫细胞染色法检测GFAP表达情况. 结果 乳黄片脑脊液能升高高氨环境中受损细胞CRL-2541的吸光度,上调GFAP的表达. 结论 乳黄片能进入血 脑脊液屏障,对高氨环境中受损的星形胶质细胞有保护作用,提示其抗肝性脑病的作用位点可能为星形胶质细胞.     

星形胶质细胞在癫痫发病中的作用研究

癫痫的发病机制十分复杂,近年来星形胶质细胞在癫痫发生发展中的关键作用逐渐显现。通过对星形胶质细胞的干预,可能为癫痫的治疗提供新的靶点。本文综述星形胶质细胞在癫痫发病中的作用研究。     

Manipulations of 5-HT activity and memory in the rat

The activity of 5-HT was manipulated by means of the peripheral injection of 5-HT reuptake inhibitors, fenfluramine and fluoxetine. These drug treatments, at doses higher than 1 mg/kg, produced retrograde amnesia in a one-trial appetitive learning task in rats. A non-specific inhibitor of 5-HT reuptake, imipramine, did not produce this amnesic effect, nor did the combination of fenfluramine with the MAOI tranylcypromine, although it produced, as expected, the "serotonergic syndrome." Results for the metabolic precursor of 5-HT, 5-HTP, also administered peripherally, were inconsistent, with amnesic effects seen at 5 and 20 mg/kg but none at 10 mg/kg.     

dBcAMP诱导的细胞分化上调大鼠星状胶质细胞内脂多糖诱导的一氧化 …

目的：研究ｄＢｃＡＭＰ诱导分化成熟后的星状胶质细胞内脂多糖诱导型一氧化氮合酶活力的诱导表达情况。方法：采用荧光分光光度法和胍胺酸生成实验考察星状胶质细胞内一氧化氮合酶的活力，并通过免疫细胞化学和光学显微镜考察细胞的分化情况。结果：经ｄＢｃＡＭＰ诱导后，星状胶质细胞分化成星型细胞，ＧＦＡＰ表达增强，ｄＢｃＡＭＰ显著增强ＬＰＳ诱导产生的亚硝酸盐水平的提高；ｄＢｃＡＭＰ／ＬＰＳ共同诱导２４ｈ后，使ＮＯＳ     

Facilitation of memory and cognition by drugs

George Heise surveys the experimental research with animals on three groups of compounds — cholinergics, nootropics, and neuromodulators — that facilitate memory and cognition in animals, with emphasis on the adequacy and logic of ‘animal models’ of normal or deficient human performance that underlie the research. Although there are compounds that dramatically improve performance in animals, the beneficial effects of these compounds on human memory or cognitive performance, while sometimes statistically significant, have been small and of questionable clinical relevance. No clearly effective ‘reference’ compound has as yet been discovered. He makes suggestions for redirecting the animal research towards more effective models.     

三七总皂苷对糖尿病肾病大鼠的肾脏保护作用及机制

目的 观察三七总皂苷(PNS)对DN的肾脏保护作用及机制.方法 36只雄性SD大鼠分成正常组、模型组、PNS干预组(均12只).4,8周末,检测血清和肾皮质的晚期糖基化终产物( AGEs)、超氧化物歧化酶(SOD)、丙二醛(MDA)以及肾皮质VEGF含量.结果 PNS干预组,血清与肾组织的MDA、AGEs和VEGF含量,均明显低于模型组(P＜O.01,P＜0.05);而SOD显著高于模型组(P＜0.05).结论 PNS可能通过抗氧化、抑制AGEs生成、下调肾组织VEGF表达,来延缓DN大鼠肾脏病变进展.     

Metrifonate,like acetylcholine,up-regulates neurotrophic activity of cultured rat astrocytes

BackgroundMetrifonate is an inhibitor of acetylcholinesterase (AChE). Several studies confirmed its positive effects on cognitive impairment in Alzheimer's disease but it was due to adverse events withdrawn from clinical trials. Based on the importance of astrocytes in physiological and pathological brain activities we investigated the impact of metrifonate and, for comparison, acetylcholine on intrinsic neurotrophic activity in these cells.MethodsMetabolic activity, intracellular adenosine 5′-triphosphate (ATP) levels and lactate dehydrogenase (LDH) release was measured to examine the impact of metrifonate on viability and integrity of cultured rat cortical astrocytes. The influence of metrifonate, acetylcholine and selective cholinergic ligands on nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) synthesis and secretion was determined by specific two-site enzyme immunoassays.ResultsExposure of cultured astrocytes to metrifonate displayed no toxic effects on cell viability. Metrifonate and acetylcholine potently and transiently elevated NGF and BDNF, but not NT-3, protein levels and secretion with different intensity and time frame of their maximal response. Stimulatory effect on NGF was mimicked by selective nicotinic receptor agonist nicotine and completely blocked by nicotinic antagonist mecamylamine. The impact on BDNF synthesis was mimicked by muscarinic receptor agonist pilocarpine and abolished by selective muscarinic antagonist scopolamine.ConclusionsMetrifonate up-regulates astrocytic NGF and BDNF synthesis in the same manner as acetylcholine, their effect depends on different cholinergic pathways. These results suggest a trophic role of metrifonate, based on a well-known neurotrophic activity of NGF and BDNF in vivo.     

Inhibitory effects of ginseng total saponins on hypoxia-induced dysfunction and injuries of cultured astrocytes

The effects of ginseng total saponins (GTS) on hypoxic damage of primary cultures of astrocytes were studied. Hypoxia was created by placing cultures in an air tight chamber that was flushed with 95% N(2)/5% CO(2) for 15 min before being sealed. Cultures showed evidence of significant cell injury after 24 h of hypoxia (increased lactate dehydrogenase (LDH) content in the culture medium, cell swelling and decreased glutamate uptake and protein content). Addition of GTS (0.1, 0.3 mg/ml) to the cultures during the exposure to hypoxic conditions produced dose-dependent inhibition of the LDH efflux. GTS (0.1, 0.3 mg/ml) also produced significant inhibition of the increased cell volume of astrocytes measured by [(3)H]O-methyl-D-glucose uptake under the hypoxic conditions. Decreased glutamate uptake and protein content was inhibited by GTS. These data suggest that GTS prevents astrocytic cell injury induced by severe hypoxiain vitro.     

Bombycis corpus extract prevents amyloid-beta-induced cytotoxicity and protects superoxide dismutase activity in cultured rat astrocytes.

Bombycis corpus(BC) or Bombyx Batryticatus, a batryticated silkworm and white-stiff silkworm, is a drug consisting of the dried larva of silkworm, Mobyz mori L., dead and stiffened due to the infection of Beauveria (Bals.) Vuill. In the present study, we have examined the protective effect of the water extracts against Amyloid- beta(A beta) 25-35 peptide-induced cytotoxicity by microscopic observation and LDH assay, and its action on antioxidative enzymes using cultured astrocyte cells. A beta 25-35-induced cell death was protected by the application of water extract of BC in a dose-dependent manner, and concentrations of 10(-6)to 10(-7)g ml(-1)showed a significant effect compared to exposure of A beta 25-35 alone. When antioxidative enzyme activities such as catalase, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione-S transferase (GST) were assayed after A beta 25-35 treatment, most enzyme activities were decreased in a similar fashion. BC treatment of A beta 25-35-treated astrocytes did not affect the enzyme activities of catalase, GSH-Px and GST. However, only SOD activity was enhanced by BC treatment and this may result from the potentiation of the antioxidative ability of BC. The protective effect of BC against cytotoxicity induced by Abeta 25-35 strongly indicates that BC could be a protective agent for free radical generating compounds, and that Abeta 25-35 is not only a potent lipid peroxide inducer, but can also cause changes in antioxidative enzymes. From the results, it was concluded that BC has a protective effect against Abeta -induced cytotoxicity in cultured astrocyte cells through the inhibition of lipid peroxidation and protection of antioxidative enzymes.