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Sericin alleviates pentylenetetrazole kindling epilepsy and associated comorbidities via modulation of GABA-T enzyme and mitochondrial activity
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作者 Sania Grover Raj Kumar Narang Shamsher Singh 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2023年第10期431-442,共12页
Objective:To assess the effect of sericin against pentylenetetrazole(PTZ)kindling epilepsy and its associated comorbidities.Methods:Epilepsy was induced with PTZ at the dose of 30 mg/kg i.p.on alternative days for 25 ... Objective:To assess the effect of sericin against pentylenetetrazole(PTZ)kindling epilepsy and its associated comorbidities.Methods:Epilepsy was induced with PTZ at the dose of 30 mg/kg i.p.on alternative days for 25 days in rats.Sericin was administered orally at the doses of 250,500,and 1000 mg/kg for 35 days.The behavioral activities were performed using an elevated plus maze,forced swim test,and Morris water maze test.A PTZ challenge test was conducted on day 32.On day 35,rats were sacrificed to perform oxidative stress,mitochondrial dysfunction,neuroinflammation,neurotransmitters,GABA-T activity,and histopathological analyses.Results:Sericin at 500 and 1000 mg/kg significantly reduced behavioral changes and neuroinflammatory cytokines,as well as improved oxidative stress,mitochondrial enzyme complex activity,neurotransmitter level,and GABA-T enzymatic activity(P<0.05).Moreover,sericin improved the neuronal survival altered by PTZ kindling in rat hippocampus.Conclusions:Sericin mitigates epilepsy-associated secondary complications possibly by the modulation of mitochondrial enzyme complexes and GABA-T enzymatic activity. 展开更多
关键词 pentylenetetrazole SERICIN GABA-T EPILEPSY ANXIETY Cognitive impairment
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Effects of Chloroquine on GFAP, PCNA and Cyclin D1 in Hippocampus and Cerebral Cortex of Rats with Seizures Induced by Pentylenetetrazole 被引量:6
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作者 张树华 朱长庚 +1 位作者 刘庆莹 王伟 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2005年第6期625-628,共4页
The effects of chloroquine on glial fibrillary acidic protein (GFAP), proliferation cell nuclear antigen (PCNA) and Cyclin D1 in hippocampus and cerebral cortex of rats with seizures induced by pentylenetetrazole ... The effects of chloroquine on glial fibrillary acidic protein (GFAP), proliferation cell nuclear antigen (PCNA) and Cyclin D1 in hippocampus and cerebral cortex of rats with seizures induced by pentylenetetrazole (PTZ) were observed in the present study. Forty-eight male adult Sprague-Dawley (SD) rats were randomly divided into control group, chloroquine intervening group, and PTZ group. The behavior and electroencephalogram (EEG) were observed and recorded. GFAP and PCNA were examined with immunohistochemistry. The content of Cyclin D1 in hippocampus and cerebral cortex was inspected with Western blot. The results showed no seizure activity in the control group, severe seizure activity in the PTZ group (Ⅳ - Ⅴ degree), and slight seizure activity ( Ⅰ -- Ⅲ degree) in the chloroquine intervening group (P〈0.05). EEG recordings showed no epileptic spikes in the control group, high amplitude with fast frequency in the PTZ group, low amplitude and slow frequency in the chloroquine intervening group. The expression of GFAP and the positive index of PCNA in the PTZ group were higher than those of control group (P 〈0.05 and P〈0.01, respectively). No differences in GFAP expression and PCNA index were observed between chloroquine intervening and control groups (P〉0.05). The content of Cyclin D1 in hippocampus and cerebral cortex was significantly higher in the PTZ group than in control and chloroquine intervening groups (P〈 0.05). Therefore, it is considered that chloroquine, by inhibiting the functions and proliferation of glial cells in the hippocampus and cerebral cortex, can alleviate the seizure activities. These results suggest that chloroquine may be an ideal anticonvulsant in preventing and treating epilepsy. 展开更多
关键词 glial fibrillary acidic protein proliferation cell nuclear antigen Cyclin D1 pentylenetetrazole CHLOROQUINE EPILEPSY
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Evaluation of the anticonvulsant activity of the essential oil of Myrothamnus moschatus in convulsion induced by pentylenetetrazole and picrotoxin
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作者 Emmanuel Randrianarivo Filippo Maggi +1 位作者 Marcello Nicoletti Philippe Rasoanaivo 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2016年第6期501-505,共5页
Objective: To evaluate the anticonvulsant effect of the essential oil of Myrothamnus moschatus(M. moschatus) in convulsion induced by pentylenetetrazole and picrotoxin in rodent models.Methods: The essential oil of th... Objective: To evaluate the anticonvulsant effect of the essential oil of Myrothamnus moschatus(M. moschatus) in convulsion induced by pentylenetetrazole and picrotoxin in rodent models.Methods: The essential oil of the aerial parts of M. moschatus was extracted by steam distillation. Thereafter, it was injected subcutaneously to rats and mice at escalating doses(0.1–0.8 m L/kg). Ten minutes after drug injection, pentylenetetrazole was injected intraperitoneally to rats and picrotoxin was administered to mice by the same route.Diazepam served as the positive control. Every single animal was placed into transparent cage and observed for convulsive behavior for 30 min by using ordinary security cameras connected to a video recorder. Death occurring for a period of 24 h was also recorded.Results: The essential oil at 0.8 m L/kg completely arrested the pentylenetetrazole-induced convulsion without any sedative effect and delayed its appearance at lower doses, but showed moderate activities on picrotoxin-induced convulsion. For the rats treated with pentylenetetrazole alone, the mortality was 100% within 1 h, but for the rats pre-treated with the essential oil, the mortality was 0%. For the mice treated with picrotoxin, the mortality rate was also 100%, while 20%–100% died in those that had been pre-treated with the oil.Conclusions: The results confirmed at least partly the traditional uses of the smoke of M. moschatus for the management of convulsion, and implied that the essential oil may inhibit the convulsion by GABAergic neuromodulation. 展开更多
关键词 Myrothamnus moschatus ESSENTIAL OIL CONVULSIONS pentylenetetrazole PICROTOXIN
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KCNQ钾离子通道开放剂的筛选及抗癫痫活性观察
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作者 李佳 王远 +2 位作者 宋超 贾庆忠 祁金龙 《中国药理学通报》 CAS CSCD 北大核心 2024年第9期1744-1752,共9页
目的筛选KCNQ通道开放活性化合物并进一步评价其抗癫痫作用。方法利用铷流出高通量筛选技术初筛,对优选化合物QO-72,复制多个动物模型,通过行为学以及脑电图(EEG)分析,结合一般药理学实验,对其有效性安全性进行初步评价,并探讨作用机制... 目的筛选KCNQ通道开放活性化合物并进一步评价其抗癫痫作用。方法利用铷流出高通量筛选技术初筛,对优选化合物QO-72,复制多个动物模型,通过行为学以及脑电图(EEG)分析,结合一般药理学实验,对其有效性安全性进行初步评价,并探讨作用机制。结果得到3个系列活性化合物共51个。化合物QO-72在MES和PTZ急性实验中,灌胃和腹腔注射可明显提高抗惊厥保护率(P<0.05,0.01),延长癫痫大发作阈值(P<0.01)。在PTZ点燃慢性癫痫模型中,QO-72腹腔注射不同剂量均可降低癫痫发作等级(P<0.01),缩短癫痫发作持续时间(P<0.01),大剂量明显提高发作保护率(P<0.01);QO-72治疗组EEG癫痫波时程明显缩短、振幅明显降低、波功率谱密度明显下降(P<0.05,0.01)。QO-72灌胃给药治疗剂量16倍或腹腔注射8倍,对小鼠协调运动、自主活动、戊巴比妥钠协同睡眠无明显影响。QO-72给药组海马区脑脊液GABA含量可明显增加(P<0.01),Glu没有明显变化(P>0.05)。结论化合物QO-72在电刺激和化学诱导的急、慢性癫痫模型上,均表现出良好抗癫痫作用,其机制除开放KCNQ通道外,可能还与增加脑内抑制性神经递质GABA含量有关。 展开更多
关键词 癫痫 KCNQ开放剂 高通量筛选 戊四唑 脑电图 一般药理学
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miR-125a-5p通过靶向STAT3减轻戊四唑诱导的癫痫大鼠神经功能障碍和炎症反应
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作者 单萍 张继龙 《中国免疫学杂志》 CAS CSCD 北大核心 2024年第7期1373-1380,共8页
目的:探讨miR-125a-5p通过靶向信号转导与转录激活因子3(STAT3)对戊四唑(PTZ)诱导的癫痫大鼠神经功能障碍和炎症反应的影响。方法:采用PTZ点燃法建立大鼠癫痫模型,并将其随机分为6组:Con组、PTZ组、PTZ+agomir NC组、PTZ+miR-125a-5p ag... 目的:探讨miR-125a-5p通过靶向信号转导与转录激活因子3(STAT3)对戊四唑(PTZ)诱导的癫痫大鼠神经功能障碍和炎症反应的影响。方法:采用PTZ点燃法建立大鼠癫痫模型,并将其随机分为6组:Con组、PTZ组、PTZ+agomir NC组、PTZ+miR-125a-5p agomir组、PTZ+miR-125a-5p agomir+pcDNA组和PTZ+miR-125a-5p agomir+pc-STAT3组,评价miR-125a-5p对大鼠癫痫持续时间、潜伏期、惊厥次数和严重程度的影响。qRT-PCR检测miR-125a-5p和STAT3 mRNA表达;改良神经系统严重程度评分(mNSS)、开场实验和Rotarod测试评价癫痫大鼠的神经功能;Morris水迷宫实验评价癫痫大鼠的认知功能;免疫染色观察海马CA1和CA3区域神经元凋亡;ELISA检测海马组织炎症因子(TNF-α、IL-6、IL-1β和IL-18)水平;Western blot检测海马组织中STAT3蛋白表达;双荧光素酶实验验证miR-125a-5p和STAT3的关系。结果:在PTZ诱导的癫痫大鼠中,miR-125a-5p表达上调,STAT3表达下调,且miR-125a-5p靶向抑制STAT3表达。与PTZ组相比,PTZ+miR-125a-5p agomir组癫痫大鼠的潜伏期缩短,癫痫评分降低,癫痫发作时间和次数减少,mNSS降低,掉落潜伏期及外围区域的移动距离、开放区域的总距离延长,逃避潜伏期显著降低,穿越平台次数及停留在目标象限的时间和游泳距离均增加,海马组织TNF-α、IL-6、IL-1β、IL-18表达降低,CA3和CA1区的NenN+细胞增多(P<0.05);STAT3过表达可逆转miR-125a-5p agomir对癫痫大鼠神经功能障碍及炎症反应的缓解作用(P<0.05)。结论:miR-125a-5p通过靶向下调STAT3,减轻PTZ诱导的癫痫大鼠神经功能障碍和炎症反应。 展开更多
关键词 miR-125a-5p 信号转导与转录激活因子3 戊四唑 癫痫 神经功能障碍 炎症
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补阳还五汤通过抑制炎症反应对创伤性癫痫小鼠的预防作用 被引量:1
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作者 和璐璐 肖琪 +7 位作者 樊慧杰 孙芮芮 贾璐 王青 金小明 马存根 于保锋 柴智 《世界中医药》 CAS 北大核心 2024年第11期1638-1643,共6页
目的:探讨补阳还五汤对创伤性癫痫小鼠模型的预防作用及可能的作用机制。方法:将30只C57BL/6小鼠按照随机数字表法分为假手术组、模型组、补阳还五汤组,每组10只。对模型组、补阳还五汤组小鼠施行皮质切割手术,假手术组只进行颅骨钻孔... 目的:探讨补阳还五汤对创伤性癫痫小鼠模型的预防作用及可能的作用机制。方法:将30只C57BL/6小鼠按照随机数字表法分为假手术组、模型组、补阳还五汤组,每组10只。对模型组、补阳还五汤组小鼠施行皮质切割手术,假手术组只进行颅骨钻孔。术后第2天,假手术组、模型组给予10 mL/kg生理盐水(灌胃治疗),补阳还五汤组给予补阳还五汤(32 g/kg)(灌胃治疗),连续干预10 d。第21天腹腔注射戊四氮(PTZ),比较各组小鼠癫痫首次大发作PTZ剂量、首次大发作潜伏期、发作等级、小发作总次数、大发作持续时间、体质量、大脑皮质组织病理形态改变及大脑皮质组织白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)蛋白表达。结果:与假手术组比较,模型组小鼠癫痫首次大发作PTZ剂量少,潜伏期短,持续时间长,发作次数多,大脑皮质神经元细胞少,尼氏小体破损严重,大脑皮质组织IL-6、IL-1β、TNF-α蛋白表达高,差异均有统计学意义(均P<0.05);与模型组比较,补阳还五汤组小鼠癫痫首次大发作PTZ剂量多,潜伏期长,发作持续时间短,发作次数少,大脑皮质神经元细胞多,排列相对紧密,尼氏小体破损轻,大脑皮质组织IL-6、IL-1β、TNF-α蛋白表达低,差异均有统计学意义(均P<0.05)。模型组小鼠癫痫发作等级较假手术组高,但差异无统计学意义(P>0.05);补阳还五汤组小鼠癫痫发作等级较模型组低,但差异无统计学意义(P>0.05)。结论:补阳还五汤可提高创伤性癫痫小鼠癫痫诱发阈值,改善大脑皮质组织病理变化,促进大脑皮质神经元细胞修复和再生;其作用机制可能与减轻大脑皮质炎症反应有关。 展开更多
关键词 补阳还五汤 创伤性癫痫 小鼠 戊四氮 神经元 尼氏小体 炎症反应 神经元修复
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痰热清注射液治疗慢性阻塞性肺病急性加重期作用机制探讨
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作者 谭标标 任薇 《中医药临床杂志》 2024年第6期1081-1087,共7页
目的:研究痰热清注射液治疗慢性阻塞性肺病急性加重期作用机制。方法:在线查询TCMSP数据库、既往文献获取黄芩、熊胆粉、山羊角、金银花、连翘等中药的主要活性成分,利用swisstargetprediction数据库获取其活性成分对应靶点;利用GeneCa... 目的:研究痰热清注射液治疗慢性阻塞性肺病急性加重期作用机制。方法:在线查询TCMSP数据库、既往文献获取黄芩、熊胆粉、山羊角、金银花、连翘等中药的主要活性成分,利用swisstargetprediction数据库获取其活性成分对应靶点;利用GeneCards、OMMI、Drug Bank等数据库获取慢性阻塞性肺病急性加重期靶点。利用Venny平台在线获取药物与疾病靶点交集,通过DAVID数据库对相交靶点进行基因本体分析和通路富集分析,使用STRING数据库构建蛋白相互作用网络,借助Cytoscapr软件行可视化处理并筛选主要活性成分、关键靶点。最后通过AutoDock vina软件将核心靶点与核心成分进行分子对接验证,并利用pymol可视化处理。结果:痰热清注射液中含主要活性成分90个,对应靶点557个;连翘、黄芩、金银花为痰热清注射液的关键作用药物;baicalein、Norwogonin、5,7,4’-Trihydroxy-8-methoxyflavone、5,2’,6’-Trihydroxy-7,8-dimethoxyflavone、(2R)-7-hydroxy-5-methoxy-2-phenylchroman-4-one、Panicolin、Skullcapflavone II、Moslosooflavone、5,7,2,5-tetrahydroxy-8,6-dimethoxyflavone、quercetin等为核心活性成分;STAT3、HSP90AA1、ESR1、SRC、EP300、AKT1、JUN、PIK3R1、RELA等靶点为蛋白互作网络中的核心靶点。结论:痰热清注射液治疗主要通过黄酮类物质调节细胞炎症反应、细胞增殖、凋亡等对慢性阻塞性肺病急性加重期发挥潜在作用。 展开更多
关键词 痰热清注射液 慢性阻塞性肺病急性加重期 网络药理学 分子对接技术 作用机制
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基于网络药理学及分子对接探讨二至丸治疗早发性卵巢功能不全的作用机制
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作者 简万妍 王艳群 +1 位作者 陈美玲 曾莉 《中国医药科学》 2024年第7期77-81,共5页
目的基于网络药理学方法探讨二至丸治疗早发性卵巢功能不全(POI)的可能分子作用机制。方法使用网络药理学平台(TCMSP)采集二至丸的有效成分和相关的基因;通过基因组注释数据平台(GeneCards)、人类孟德尔遗传数据库(OMIM)数据库获取POI... 目的基于网络药理学方法探讨二至丸治疗早发性卵巢功能不全(POI)的可能分子作用机制。方法使用网络药理学平台(TCMSP)采集二至丸的有效成分和相关的基因;通过基因组注释数据平台(GeneCards)、人类孟德尔遗传数据库(OMIM)数据库获取POI疾病靶点;用蛋白互作网络数据库(STRING)构建蛋白质相互作用网络(PPI),通过CytoHubba筛选核心靶点。使用生物学信息注释数据库(DAVID)平台进行富集分析,采用Cytoscape 3.10.0软件进行拓扑学分析,利用AutoDockTools进行分子对接。结果二至丸内最主要的有效成分为槲皮素、木犀草素、山柰酚、刺槐素等,其中的AKT1、TP53等是关键靶点,包含的通路主要为PI3K-Akt信号通路、流体剪切应力和动脉粥样硬化信号通路等。分子对接验证大部分靶点与成分能进行有效结合。结论揭示二至丸能够经多种成分、靶点及多条信号通路对POI发挥协同治疗作用。 展开更多
关键词 二至丸 早发性卵巢功能不全 网络药理学 分子对接
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Anti-epileptic effect of morin against experimental pentylenetetrazol-induced seizures via modulating brain monoamines and oxidative stress
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作者 Amit D.Kandhare Anwesha A.Mukherjee Subhash L.Bodhankar 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2018年第7期352-359,共8页
Objective: To evaluate the protective effect of morin against pentylenetetrazol(PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice(18-22 g) was used to induce convulsions by intraperitoneal(i.p.... Objective: To evaluate the protective effect of morin against pentylenetetrazol(PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice(18-22 g) was used to induce convulsions by intraperitoneal(i.p.) administration of PTZ(90 mg/kg). Mice were either pretreated with morin(10, 20 and 40 mg/kg) or vehicle(distilled water, 10 mg/kg) 45 min before PTZ administration. Various behavioral and biochemical parameters were assessed. Results: PTZ administration resulted in significant production(P<0.001) of tonic-clonic conclusion and mortality in mice. PTZ-induced increase in the duration of convulsion, onset of convulsion and mortality was inhibited significantly by morin(20 and 40 mg/kg) administration. The PTZinduced decrease in brain GABA, dopamine and Na+K+ATPase levels and increase in xanthine oxidase activity were inhibited significantly by morin(20 and 40 mg/kg) treatment. The increased levels of malondialdehyde and nitric oxide level were significantly decreased by morin(20 and 40 mg/kg) treatment. Also, reduced levels of superoxide dismutase and glutathione were increased significantly by morin treatment. Conclusions: Results of the present study indicate that morin showed its anti-convulsant effect via modulating the levels of brain GABA, Na^+K^+ATPase, and oxido-nitrosative stress. Thus, morin can be a potential candidate for further clinical evaluations as an anti-epileptic agent. 展开更多
关键词 Brain GABA Epilepsy MORIN Nitric oxide pentylenetetrazol Oxidative stress Xanthine oxidase
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Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics
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《World Journal of Gastrointestinal Pharmacology and Therapeutics》 CAS 2010年第5期123-123,共1页
Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastrointestinal
关键词 reviewers EXPERTISE grateful evaluating editing submitted IMMUNOLOGY rejected pharmacol Australia
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Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics
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《World Journal of Gastrointestinal Pharmacology and Therapeutics》 CAS 2011年第1期9-9,共1页
Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal
关键词 reviewers EXPERTISE grateful evaluating EDITING submitted Surgery rejected pharmacol Australia
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Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics
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《World Journal of Gastrointestinal Pharmacology and Therapeutics》 CAS 2012年第3期36-36,共1页
We acknowledge our sincere thanks to our reviewers. Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of our World Series Journals. Both the editors ... We acknowledge our sincere thanks to our reviewers. Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of our World Series Journals. Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers 展开更多
关键词 reviewers EXPERTISE submitted grateful Australia REVIEWING Brazil NEUROSCIENCE Assistant pharmacol
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Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics
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《World Journal of Gastrointestinal Pharmacology and Therapeutics》 CAS 2011年第6期52-52,共1页
Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics. The editors
关键词 reviewers EXPERTISE grateful evaluating editing submitted NEUROSCIENCE VANCOUVER rejected pharmacol
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Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics
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《World Journal of Gastrointestinal Pharmacology and Therapeutics》 CAS 2012年第5期83-83,共1页
We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of ... We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers for reviewing the articles(either published or rejected) over the past period of time. 展开更多
关键词 reviewers EXPERTISE submitted grateful REVIEWING rejected Australia ASSISTANT pharmacol Surgery
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Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics
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《World Journal of Gastrointestinal Pharmacology and Therapeutics》 CAS 2012年第1期7-7,共1页
Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics.The editors and authors of the ar... Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics.The editors and authors of the articles submitted to the journal are grateful to the 展开更多
关键词 reviewers EXPERTISE submitted grateful editing evaluating Australia NEUROSCIENCE ASSISTANT pharmacol
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Anticonvulsant activity of allopregnanolone against pentylenetetrazol- induced seizures in rodents
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作者 鲁映青 于榕 《现代康复》 CSCD 2001年第1期155-155,157,共2页
Objective To examine the protective effects of allopregnanolone against pentylenetetrazol- induced seizures. Methods The protective effects of allopregnanolone against pentylenetetrazol- induced seizures were studie... Objective To examine the protective effects of allopregnanolone against pentylenetetrazol- induced seizures. Methods The protective effects of allopregnanolone against pentylenetetrazol- induced seizures were studied in C57 mice and SD rats 15 minutes after vehicle or drug intraperitoneal (ip) administration. Results The pretreatment with the allopregnanolone produced a dose- dependent protective effect against pentylenetetrazol- induced seizures. The potencies (ED50 values) were 4.7 mg/kg and 9.8 mg/kg for mice and rats, respectively. Conclusion Allopregnanolone has anticonvulsant activity against pentylenetetrazol- induced seizures in rodents. 展开更多
关键词 别孕烯醇酮 卡地阿性 ED50 癫痫发作
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Sphingosine 1-phosphate receptor 1 regulates bloodbrain barrier permeability in epileptic mice 被引量:3
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作者 Li-Xiang Yang Yuan-Yuan Yao +3 位作者 Jiu-Rong Yang Hui-Lin Cheng Xin-Jian Zhu Zhi-Jun Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第8期1763-1769,共7页
Destruction of the blood-brain barrier is a critical component of epilepsy pathology.Several studies have demonstrated that sphingosine 1-phosphate receptor 1 contributes to the modulation of vascular integrity.Howeve... Destruction of the blood-brain barrier is a critical component of epilepsy pathology.Several studies have demonstrated that sphingosine 1-phosphate receptor 1 contributes to the modulation of vascular integrity.However,its effect on blood-brain barrier permeability in epileptic mice remains unclear.In this study,we prepared pilocarpine-induced status epilepticus models and pentylenetetrazol-induced epilepsy models in C57BL/6 mice.S1P1 expression was increased in the hippocampus after status epilepticus,whereas tight junction protein expression was decreased in epileptic mice compared with controls.Intraperitoneal injection of SEW2871,a specific agonist of sphingosine-1-phosphate receptor 1,decreased the level of tight junction protein in the hippocampus of epileptic mice,increased blood-brain barrier leakage,and aggravated the severity of seizures compared with the control.W146,a specific antagonist of sphingosine-1-phosphate receptor 1,increased the level of tight junction protein,attenuated blood-brain barrier disruption,and reduced seizure severity compared with the control.Furthermore,sphingosine 1-phosphate receptor 1 promoted the generation of interleukin-1βand tumor necrosis factor-αand caused astrocytosis.Disruption of tight junction protein and blood-brain barrier integrity by sphingosine 1-phosphate receptor 1 was reversed by minocycline,a neuroinflammation inhibitor.Behavioral tests revealed that sphingosine 1-phosphate receptor 1 exacerbated epilepsy-associated depression-like behaviors.Additionally,specific knockdown of astrocytic S1P1 inhibited neuroinflammatory responses and attenuated blood-brain barrier leakage,seizure severity,and epilepsy-associated depression-like behaviors.Taken together,our results suggest that astrocytic sphingosine 1-phosphate receptor 1 exacerbates blood-brain barrier disruption in the epileptic brain by promoting neuroinflammation. 展开更多
关键词 adeno-associated virus ASTROCYTES blood-brain barrier EPILEPSY epilepsy-associated depression-like behavior NEUROINFLAMMATION pentylenetetrazol PILOCARPINE tight junction
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《医宗金鉴·正骨心法要旨》中治疗伤科瘀肿疼痛方剂的用药规律分析 被引量:2
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作者 黄明翥 周红海 +2 位作者 何心愉 徐涛 吴周统 《中医正骨》 2023年第10期37-41,共5页
目的:分析《医宗金鉴·正骨心法要旨》中治疗伤科瘀肿疼痛方剂的用药规律。方法:收集《医宗金鉴·正骨心法要旨》中治疗伤科瘀肿疼痛的方剂,对组方中药物的出现频次及药性、药味、归经、功效进行统计,分析用药规律。结果:共收... 目的:分析《医宗金鉴·正骨心法要旨》中治疗伤科瘀肿疼痛方剂的用药规律。方法:收集《医宗金鉴·正骨心法要旨》中治疗伤科瘀肿疼痛的方剂,对组方中药物的出现频次及药性、药味、归经、功效进行统计,分析用药规律。结果:共收集到《医宗金鉴·正骨心法要旨》中治疗瘀肿疼痛的内服、外用方剂57首,涉及中药179味。出现频次≥5的药物有35味,当归出现频次最多。药性出现频次较高的为温、寒、平,药味出现频次较高的为辛、苦、甘,归经主要归肝经、脾经、心经,药物功效主要为补虚、活血、清热。关联药物数最多的药物是当归,规则支持度最高的药物组合为川芎-当归;增益最高的药物组合为生姜-人参、甘草。核心药物组合有4组,分别为人参-生姜-大枣-茯苓-白术、柴胡-栀子-半夏-黄芩、当归-川芎-熟地黄-白芍、血竭-木香-酒。结论:《医宗金鉴·正骨心法要旨》中治疗伤科瘀肿疼痛的方剂多采用性温、味辛、归肝经的药物,核心药物组合以健脾益气、疏肝清火、补血活血、活血止痛药物为主,用药规律符合其专从血论、气血并重、消补并用的治伤思想。 展开更多
关键词 中医药学文献 《医宗金鉴》 中医骨伤科疾病 方剂构成 数据挖掘 聚类分析
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4⁃辛基衣康酸通过Keap1/Nrf2/GPX4通路减少癫痫大鼠海马神经元铁死亡
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作者 章朝 王梓 +5 位作者 宁瑞 吴淑华 胡忠波 郭翀 郭科 李建民 《神经解剖学杂志》 CAS CSCD 2023年第4期443-451,共9页
目的:探讨4⁃辛基衣康酸(4⁃OI)对癫痫大鼠海马神经元铁死亡的影响。方法:雄性SD大鼠45只,随机分为生理盐水组、戊四氮组(PTZ)和4⁃辛基衣康酸和戊四氮联合治疗组(4⁃OI+PTZ)。观察记录各组大鼠癫痫发作程度行为学及脑电图变化,应用尼氏染... 目的:探讨4⁃辛基衣康酸(4⁃OI)对癫痫大鼠海马神经元铁死亡的影响。方法:雄性SD大鼠45只,随机分为生理盐水组、戊四氮组(PTZ)和4⁃辛基衣康酸和戊四氮联合治疗组(4⁃OI+PTZ)。观察记录各组大鼠癫痫发作程度行为学及脑电图变化,应用尼氏染色观察海马区神经元变化,膜片钳技术评估海马CA1区的神经元兴奋性,试剂盒测定海马区铁离子、谷胱甘肽(GSH)和丙二醛(MDA)水平,采用免疫组化与Western Blot检测各组大鼠海马区神经元核因子红细胞2相关因子2(Nrf2)、Klech样ECH关联蛋白1(Keap1)、谷胱甘肽过氧化物酶4(GPX4)、前列腺素内过氧化物合成酶2(PTGS2)的表达情况。结果:与生理盐水组比较,PTZ组癫痫样发作明显,神经元尼氏体的含量显著减少,神经元的兴奋性显著增加,海马区铁离子、MDA、PTGS2与Keap1的表达明显升高,GSH、Nrf2、GPX4的表达明显下降(P<0.05);与癫痫组相比,4⁃OI处理组癫痫发作等级降低,神经元尼氏体的含量显著增加,神经元的兴奋性显著下降,海马区铁离子、MDA、PTGS2与Keap1的表达明显下降,GSH、Nrf2与GPX4的表达明显升高(P<0.05)。结论:4⁃OI可以通过抑制癫痫模型大鼠海马组织中Keap1的活性,进而上调Nrf2和GPX4表达,抑制神经元铁死亡并缓解癫痫发作。 展开更多
关键词 癫痫 戊四氮 Keap1/Nrf2/Gpx4通路 铁死亡 4⁃辛基衣康酸 大鼠
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基于iTRAQ技术对戊四氮点燃癫痫大鼠海马组织的蛋白质组学分析
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作者 张鹏 张丽 +1 位作者 熊红丽 朱士胜 《神经解剖学杂志》 CAS CSCD 2023年第6期649-656,共8页
目的:筛选癫痫大鼠海马组织差异表达蛋白(DEPs),为进一步探索癫痫的发病机制和药物治疗靶点提供思路。方法:采用戊四氮(PTZ)诱导建立SD大鼠癫痫模型(PTZ组),利用同位素标记相对和绝对定量(iTRAQ)联合LC-MS/MS技术检测大鼠海马组织蛋白质... 目的:筛选癫痫大鼠海马组织差异表达蛋白(DEPs),为进一步探索癫痫的发病机制和药物治疗靶点提供思路。方法:采用戊四氮(PTZ)诱导建立SD大鼠癫痫模型(PTZ组),利用同位素标记相对和绝对定量(iTRAQ)联合LC-MS/MS技术检测大鼠海马组织蛋白质谱,以PTZ组对control组蛋白表达量变化倍数>1.5或<0.67且P<0.05为标准筛选DEPs,并对DEPs进行基因本体(GO)功能注释和京都基因与基因百科全书(KEGG)通路富集等生物信息学分析。结果:共筛选出80个显著DEPs,其中上调39个,下调41个。GO分析显示:上调的DEPs主要涉及细胞对神经生长因子刺激的反应、轴突发育、细胞表面受体信号通路、神经元迁移、肌动蛋白细丝解聚和信号转导等生物过程;下调的DEPs主要涉及三羧酸循环、柠檬酸盐代谢过程、丙酮酸-乙酰辅酶A生物合成过程、草酰乙酸代谢过程、粘附聚集体的调节等生物过程。KEGG通路富集分析显示:上调的DEPs主要参与腺苷酸活化蛋白激酶(AMPK)信号通路、肌动蛋白细胞骨架的调节、鞘脂信号通路、苯丙氨酸代谢和胰岛素信号通路等5条信号通路;下调的DEPs主要参与柠檬酸循环、碳代谢、乙醛酸和二羧酸代谢、代谢途径、氨基酸的生物合成和肌萎缩侧索硬化症等6条信号通路。结论:本研究通过iTRAQ蛋白质组学方法筛选出了癫痫海马组织的DEPs,对DEPs进行生物信息学分析所富集的代谢通路可能与癫痫的发病密切相关。 展开更多
关键词 癫痫 蛋白质组学 同位素标记相对和绝对定量 生物信息学分析 戊四氮点燃模型 大鼠
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