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移植GDNF基因修饰的神经干细胞对大鼠脑卒中的神经保护作用 被引量:32
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作者 陈波 高小青 +7 位作者 杨朝鲜 孙珠蕾 闫乃红 庞源广 袁淼 陈贵军 谭树凯 袁琼兰 《解剖学杂志》 CAS CSCD 北大核心 2009年第3期286-290,312,共6页
目的:探讨移植胶质细胞源性神经营养因子(GDNF)基因修饰的神经干细胞(NSCs)是否比单纯NSCs移植对脑卒中有更好的神经保护。方法:用GDNF重组质粒转染NSCs,构建过表达GDNF的NSCs(GDNF/NSCs)。插线法制备大鼠脑缺血卒中模型,再... 目的:探讨移植胶质细胞源性神经营养因子(GDNF)基因修饰的神经干细胞(NSCs)是否比单纯NSCs移植对脑卒中有更好的神经保护。方法:用GDNF重组质粒转染NSCs,构建过表达GDNF的NSCs(GDNF/NSCs)。插线法制备大鼠脑缺血卒中模型,再灌注3d,脑立体定位分别移植NSCs、GDNF/NSCs以及生理盐水到同侧侧脑室,实验分为GDNF/NSCs组、NSCs组和对照组。再灌注第1、2、3、5和7周处死大鼠,用改良的神经功能缺失评分和H-E染色分别评估大鼠神经功能和脑梗死体积;免疫组织化学显色观察移植的NSCs数量与分布和突触蛋白Syn、PSD-95在脑组织的表达。结果:再灌注2、3周,GDNF/NSCs组较NSCs组神经功能恢复更好。在各时间点GDNF/NSCs和NSCs组大鼠脑缺血体积较对照组显著减小;GDNF/NSCs组的NSCs细胞数量较NSCs组显著增多。再灌注2和3周,GDNF/NSCs组Syn免疫阳性产物比NSCs组显著增加;各时间点GDNF/NSCs组的PSD-95免疫阳性产物比NSCs组显著增加。结论:GDNF基因修饰的NSCs比NSCs对大鼠脑卒中有更好的神经保护作用。 展开更多
关键词 神经干细胞 移植 基因治疗 神经保护 胶质细胞源性神经营养因子 脑卒中 突触蛋白
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电针对帕金森病模型大鼠GDNF及其功能性受体Ret表达的影响 被引量:28
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作者 王彦春 程宇核 +6 位作者 马骏 甘水咏 王述菊 周华 杜艳军 杨旻 沈峰 《中国针灸》 CAS CSCD 北大核心 2010年第9期739-743,共5页
目的:探讨电针治疗帕金森病(PD)的作用机制。方法:将50只Wistar大鼠随机分为正常组、假手术组、模型组、风府太冲组和双固一通组,以6-羟基多巴胺右侧纹状体微量注射法制备偏侧PD大鼠旋转模型,假手术组以生理盐水替代6-羟基多巴胺进行微... 目的:探讨电针治疗帕金森病(PD)的作用机制。方法:将50只Wistar大鼠随机分为正常组、假手术组、模型组、风府太冲组和双固一通组,以6-羟基多巴胺右侧纹状体微量注射法制备偏侧PD大鼠旋转模型,假手术组以生理盐水替代6-羟基多巴胺进行微量注射。正常组、假手术组、模型组不做任何治疗;风府太冲组在造模的基础上电针"风府""太冲"穴,双固一通组在造模基础上电针"风府""太冲""关元""足三里"4穴,两组均每日治疗1次,共治疗2周。对比观察针刺"风府""太冲"和"双固一通"取穴法对PD模型大鼠胶质细胞源性神经营养因子(GDNF)及其功能性受体Ret表达的影响。采用免疫组化法检测GDNF阳性细胞数量,以免疫印迹法检测Ret含量。结果:两电针组GDNF阳性细胞数量比其他组显著增加(均P<0.01),双固一通组作用强于风府太冲组(P<0.01);两电针组Ret含量亦显著高于其他组(均P<0.01)。结论:电针治疗能使PD大鼠黑质和纹状体GDNF表达增强,使黑质Ret高表达,说明电针不仅能提高GDNF的表达水平,还能提高GDNF的作用效应,"双固一通"取穴在提高GDNF表达方面较单纯取"风府""太冲"穴作用强。 展开更多
关键词 帕金森病 电针 胶质细胞源性神经营养因子
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Acupuncture promotes functional recovery after cerebral hemorrhage by upregulating neurotrophic factor expression 被引量:27
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作者 Dan Li Qiu-Xin Chen +4 位作者 Wei Zou Xiao-Wei Sun Xue-Ping Yu Xiao-Hong Dai Wei Teng 《Neural Regeneration Research》 SCIE CAS CSCD 2020年第8期1510-1517,共8页
Acupuncture is widely used in the treatment of cerebral hemorrhage,and it improves outcomes in experimental animal models and patients.However,the mechanisms underlying the effectiveness of acupuncture treatment for c... Acupuncture is widely used in the treatment of cerebral hemorrhage,and it improves outcomes in experimental animal models and patients.However,the mechanisms underlying the effectiveness of acupuncture treatment for cerebral hemorrhage are still unclear.In this study,a model of intracerebral hemorrhage was produced by injecting 50μL autologous blood into the caudate nucleus in Wistar rats.Acupuncture at Baihui(DU20)and Qubin(GB7)acupoints was performed at a depth of 1.0 inch,12 hours after blood injection,once every 24 hours.The needle was rotated at 200 r/min for 5 minutes,For each 30-minute session,needling at 200 r/min was performed for three sessions,each lasting 5 minutes.For the positive control group,at 6 hours,and 1,2,3 and 7 days after induction of hemorrhage,the rats were intraperitoneally injected with 1 mL aniracetam(0.75 mg/mL),three times a day.The Bederson behavioral test was used to assess palsy in the contralateral limbs.Western blot assay was used to examine the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia.Immunohistochemistry was performed to count the number of Nestin-and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia.Acupuncture effectively reduced hemorrhage and brain edema,elevated the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia,and increased the number of Nestin-and glial cell line-derived neurotrophic factor-positive cells in the basal ganglia.Together,these findings suggest that acupuncture promotes functional recovery after cerebral hemorrhage by increasing the expression of neurotrophic factors.The study was approved by the Committee for Experimental Animals of Heilongjiang Medical Laboratory Animal Center(approval No.2017061001)on June 10,2017. 展开更多
关键词 ACUPUNCTURE basic fibroblast growth factor brain cell protection cerebral hemorrhage electron microscope glial cell line-derived neurotrophic factor immunohistochemistry NESTIN western blot assay
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小剂量丙戊酸镁对精神分裂症阳性症状病人认知功能及血清脑源性、胶质源性神经营养因子水平的影响 被引量:27
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作者 夏庆润 刘超 +1 位作者 杨魁 徐丹 《安徽医药》 CAS 2019年第10期2082-2086,共5页
目的探讨小剂量丙戊酸镁增效治疗对精神分裂症(SCH)阳性症状病人认知功能及血清脑源性神经营养因子(BDNF)和胶质源性神经营养因子(GDNF)水平的影响。方法选取沈阳市精神卫生中心自2014年3月至2016年3月收治的90例SCH病人作为研究对象,... 目的探讨小剂量丙戊酸镁增效治疗对精神分裂症(SCH)阳性症状病人认知功能及血清脑源性神经营养因子(BDNF)和胶质源性神经营养因子(GDNF)水平的影响。方法选取沈阳市精神卫生中心自2014年3月至2016年3月收治的90例SCH病人作为研究对象,采用随机数字表法分为两组:对照组(n=45)应用氯氮平与安慰剂治疗,观察组(n=45)应用氯氮平与小剂量丙戊酸镁治疗,两组疗程均为12周。比较两组临床疗效,治疗前及治疗后评价阳性和阴性症状量表(PANSS)评分、改良版威期康星卡片分类测验(M?WCST)、连线测验(TMT)、词汇流畅性测验(VFT)评分;治疗前后测定血清BDNF和GDNF水平。结果治疗后观察组总有效率为95.56%显著高于对照组的77.78%(Z=7.867,χ^2=6.154,P<0.05);治疗后,观察组的PANSS、TMT、M?WCST中错误数、持续错误数与非持续错误数均显著低于对照组(t=6.594,9.494,4.980,6.838;P<0.05),M?WCST中正确数、正确分类数均显著高于对照组(t=7.985,12.836;P<0.05);治疗后,观察组的血清BDNF为(11.78±3.01)μg/L、GDNF水平为(553.71±102.24)pg/mL,两项指标均显著高于对照组BDNF(10.04±2.43)μg/L、GDNF(466.69±75.98)pg/mL(t=3.017,4.583;P<0.05);两组总不良反应率比较差异无统计学意义(χ^2=0.756,P>0.05)。结论小剂量丙戊酸镁辅助治疗SCH安全有效,对认知功能损害具有部分改善作用,其机制可能与上调血清BDNF、GDNF表达有关。 展开更多
关键词 精神分裂症 氯氮平 丙戊酸镁 脑源性神经营养因子 胶质细胞源性神经营养因子 认知障碍 治疗结果
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胶质源性神经营养因子体外诱导小鼠胚胎中脑神经干细胞分化的研究 被引量:19
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作者 丁继固 丁文杰 +1 位作者 李光 赵克勇 《中国康复医学杂志》 CAS CSCD 北大核心 2008年第4期341-343,I0001,共4页
目的:探索胶质源性神经营养因子(GDNF)在体外诱导小鼠胚胎中脑神经干细胞(M-NSCs)分化成多巴胺能神经元的培养方法,为M-NSCs移植治疗帕金森病(PD)提供实验依据。方法:在有血清条件下体外培养鼠胚M-NSCs,予以GDNF作诱导分化。TH免疫细胞... 目的:探索胶质源性神经营养因子(GDNF)在体外诱导小鼠胚胎中脑神经干细胞(M-NSCs)分化成多巴胺能神经元的培养方法,为M-NSCs移植治疗帕金森病(PD)提供实验依据。方法:在有血清条件下体外培养鼠胚M-NSCs,予以GDNF作诱导分化。TH免疫细胞化学鉴定,流式细胞术检测TH-ir阳性神经元的百分率。结果:M-NSCs向多巴胺能神经元分化的阳性率经流式细胞术检测结果,两组TH-ir阳性细胞比率A组(实验组,6只)为13.53%±1.53%;B组(对照组,6只)3.46%±0.77%,两组比较差异有显著性意义(P<0.01)。结论:GDNF可促进M-NSCs分化成多巴胺能神经元。 展开更多
关键词 中脑神经干细胞 多巴胺能神经元 胶质源性神经营养因子 酪氨酸羟化酶
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胚胎神经干细胞移植及胶质细胞源性神经营养因子对大鼠脊髓损伤的修复作用 被引量:11
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作者 孙勇 侍坚 +2 位作者 富赛里 陆佩华 徐晓明 《生理学报》 CAS CSCD 北大核心 2003年第3期349-354,共6页
将胚胎神经干细胞 (neuralstemcells,NSCs)移植至成年大鼠损伤的脊髓 ,观察移植后NSCs的存活、迁移以及损伤后的功能恢复。实验结果显示 :动物NSCs移植 4周后 ,斜板实验平均角度和运动评分结果比对照组均有明显增高 (P <0 0 5 ) ,... 将胚胎神经干细胞 (neuralstemcells,NSCs)移植至成年大鼠损伤的脊髓 ,观察移植后NSCs的存活、迁移以及损伤后的功能恢复。实验结果显示 :动物NSCs移植 4周后 ,斜板实验平均角度和运动评分结果比对照组均有明显增高 (P <0 0 5 ) ,而脊髓损伤 (spinalcordinjury,SCI)处的空洞面积显著减小 (P <0 0 5 ) ;在NSCs中加入胶质细胞源性的神经营养因子 (glialcellline derivedneurotrophicfactor,GDNF)后 ,上述改变更加显著。移植后的NSCs不仅能存活 ,而且向损伤的头端和尾端迁移达 3mm之远。这些结果表明 ,移植的NSCs不仅可以存活、迁移 ,还可减小SCI空洞面积 ,促进动物神经功能的恢复 ;此外 。 展开更多
关键词 脊髓损伤 胚胎神经干细胞 移植 胶质细胞源性的神经营养因子
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Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro 被引量:15
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作者 Chang-Xiang Li Xue-Qian Wang +3 位作者 Fa-Feng Cheng Xin Yan Juan Luo Qing-Guo Wang 《Neural Regeneration Research》 SCIE CAS CSCD 2019年第11期1941-1949,共9页
Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin an... Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression o 展开更多
关键词 hyodeoxycholic acid oxygen glucose deprivation and REOXYGENATION blood-brain barrier permeability anti-oxidative anti-inflammatory ANTI-APOPTOTIC BRAIN-derived neurotrophic factor glial cell line-derived neurotrophic factor ischemic stroke in vitro NEUROVASCULAR unit
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蛛网膜下腔注射胶质细胞源性神经营养因子对大鼠神经病理性痛的影响 被引量:16
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作者 贾东林 吴新民 张利萍 《中国疼痛医学杂志》 CAS CSCD 2009年第4期221-225,共5页
目的:探讨蛛网膜下腔注射胶质细胞源性神经营养因子(glial cell line-derived neurotrophicfactor,GDNF)对大鼠脊神经结扎神经源性痛的影响。方法:采用大鼠L5-6脊神经结扎模型,将SD雄性大鼠随机分为正常组(n=6);假手术组(n=10)... 目的:探讨蛛网膜下腔注射胶质细胞源性神经营养因子(glial cell line-derived neurotrophicfactor,GDNF)对大鼠脊神经结扎神经源性痛的影响。方法:采用大鼠L5-6脊神经结扎模型,将SD雄性大鼠随机分为正常组(n=6);假手术组(n=10);单纯脊神经结扎(spinal nerve ligation,SNL)组(n=10):蛛网膜下腔注射生理盐水;GDNF治疗组(n=10):蛛网膜下腔注射GDNF。大鼠脊神经结扎后不同时间点进行行为学评估,以引起50%缩足的机械刺激阈值评价机械性痛觉超敏,5min内在5±1℃冷板上的缩足次数反映冷诱发的持续性疼痛。结果:各组术前基础机械痛阈和冷刺激痛阈比较差异无统计学意义(P〉0.05)。与假手术组相比,SNL组术后第1d开始出现机械痛阈和冷刺激痛阈降低(P〈0.05),一直持续到第14d,GDNF组术后7、14d时冷刺激痛阈差异无统计学意义(P〉0.05);与SNL组相比,GDNF组术后第3d时机械痛阈升高,第5d时冷刺激痛阈升高(P〈0.05),均持续到术后14d。结论:蛛网膜下腔注射GDNF能减轻神经病理性疼痛大鼠机械性痛敏和冷诱发的持续性疼痛。 展开更多
关键词 胶质细胞源性神经营养因子 神经病理性疼痛 镇痛 大鼠
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Electroacupuncture promotes the recovery of motor neuron function in the anterior horn of the injured spinal cord 被引量:15
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作者 Jian-hui Yang Jian-guo Lv +1 位作者 Hui Wang Hui-yong Nie 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第12期2033-2039,共7页
Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury... Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury was established by compressing the T8-9 segments using a modified Nystrom method.Twenty-four hours after injury,Zusanli(ST36),Xuanzhong(GB39),Futu(ST32)and Sanyinjiao(SP6)were stimulated with electroacupuncture.Rats with spinal cord injury alone were used as controls.At 2,4 and 6 weeks after injury,acetylcholinesterase(ACh E)activity at the site of injury,the number of medium and large neurons in the spinal cord anterior horn,glial cell line-derived neurotrophic factor(GDNF)m RNA expression,and Basso,Beattie and Bresnahan locomotor rating scale scores were greater in the electroacupuncture group compared with the control group.These results demonstrate that electroacupuncture increases ACh E activity,up-regulates GDNF m RNA expression,and promotes the recovery of motor neuron function in the anterior horn after spinal cord injury. 展开更多
关键词 nerve regeneration spinal cord injury ELECTROACUPUNCTURE spine injury secondaryinjury ACUPOINT motor neurons ACETYLCHOlineSTERASE glial cell line-derived neurotrophic factor inclined board test Basso Beattie and Bresnahan locomotor rating scale functional recovery neuralregeneration
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神经营养因子基因修饰的神经干细胞在帕金森病大鼠模型中的治疗作用 被引量:14
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作者 徐胜利 周明 陈彪 《中华老年医学杂志》 CAS CSCD 北大核心 2010年第1期58-62,共5页
目的观察人胶质细胞源性神经营养因子(GDNF)转染的大鼠神经于细胞移植对帕金森病(PD)模型大鼠的治疗作用。方法制备PD大鼠模型并将成功模型分为PD模型组、神经干细胞组和GDNF基因修饰神经干细胞组。细胞移植后,动态观察动物行为学... 目的观察人胶质细胞源性神经营养因子(GDNF)转染的大鼠神经于细胞移植对帕金森病(PD)模型大鼠的治疗作用。方法制备PD大鼠模型并将成功模型分为PD模型组、神经干细胞组和GDNF基因修饰神经干细胞组。细胞移植后,动态观察动物行为学变化,定量分析黑质多巴胺能神经元、纹状体多巴胺及其代谢产物的变化。结果GDNF基因修饰神经于细胞移植能有效改善实验动物的行为学表现,细胞移植后第5周时,PD模型组、神经干细胞组和GDNF基因修饰的神经于细胞组90min内的旋转圈数分别为(993.9±159.1)圈、(956.7±136.3)圈和(433.6±100.9)圈,GDNF基因修饰的神经干细胞组可显著减少PD模型大鼠向损伤侧旋转的圈数(F=95.694,P=0.000);第7周时,PD模型组的90min内的旋转圈数为(964.2±152.0)圈,神经干细胞对照组和GDNF基因修饰的神经干细胞组分别为(909.2±136.3)圈和(399.4±84.4)圈(F=106.134,p=0.000);第9周时,PD模型组、神经干细胞组和GDNF基因修饰的神经干细胞组90min内的旋转圈数分别为(909.5±152.2)圈、(865.5±129.1)圈和(312.2±63.7)圈(F=151.100,P=0.000)。GDNF基因修饰神经于细胞移植能有效提高损伤侧纹状体内的多巴胺及其代谢产物水平,PD模型组、神经干细胞组和GDNF基因修饰干细胞组毒素注射侧多巴胺含量分别为(3.3±0.3)ng/mg组织、(3.7±1.3)ng/mg组织和(7.5±0.8)ng/mg组织,GDNF基因修饰的干细胞组多巴胺水平明显高于神经干细胞组和PD模型组(F--59.543,P一0.000);GDNF基因修饰神经干细胞组二羟基苯乙酸水平明显高于神经干细胞组和PD模型组,分别为(o.9±0.1)ng/mg组织、(0.6±0.2)ng/mg组织和(0.5±0.1)ng/mg组织(F一17.293,P一0.000);PD模型组、神经干细胞组和GDNF基因� 展开更多
关键词 帕金森病 胶质细胞源性神经营养因子 干细胞移植 基因疗法
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Safflower Extract and Aceglutamide Injection Promoting Recovery of Peripheral Innervations via Vascular Endothelial Growth Factor-B Signaling in Diabetic Mice 被引量:13
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作者 Dan Li You-Gang Chen +2 位作者 Cui-Juan Zhang Jing Tian Xia Li 《Chinese Medical Journal》 SCIE CAS CSCD 2017年第23期2829-2835,共7页
Background: Safflower extract and aceglutamide (SA) has been used clinically for the treatment of cerebrovascular diseases such as cerebral embolism, hemorrhage, and mental deterioration. This study aimed to invest... Background: Safflower extract and aceglutamide (SA) has been used clinically for the treatment of cerebrovascular diseases such as cerebral embolism, hemorrhage, and mental deterioration. This study aimed to investigate the effect and mechanism of SA injection in the recovery of peripheral innervations of diabetic mice. Methods: The C57BL/6 male mice were divided into four groups: normal control group (n = 44), diabetic group (n = 44), diabetic + SA group (diabetic mice treated with SA injection, n = 44), and diabetic + SA + vascular endothelial growth factor receptor (VEGFR)1-BL group (diabetic mice treated with SA injection and VEGFR 1 blocking antibody n = 24). The streptozotocin-induced diabetic mice model and injured peripheral nerve mice model were built. The mice with injured peripheral nerves were intraperitonealy administered with SA injection for successive 21 days. The corneal sensitivity, number of corneal nerve fibers, and contents of vascular endothelial growth factor (VEGF)-B and various neurotrophic factors such as nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) in corneal tissue of four groups were observed. Results: The diabetic group showed decreased number of corneal nerve fibers, compared with the control group (P = 0.002). And compared with the diabetic group, the diabetic + SA group showed a significant increase in the number of nerve fibers (P = 0.024) and the contents of VEGF-B,NGF,andGDNFinthecornea(allP〈0.05).However,whenthediabeticmiceweretreatedwiththeblockingantibodiesspecializedfor VEGF-B receptor, the neutralization ofVEGFR-1 completely abolished the increased expression of NGF and GDNF stimulated by SAinjection. Conclusions: SA injection could reduce the nerve injury caused by diabetic peripheral neuropathy, and its protective effect might be associated with the promotion of the expressions of VEGF-B, NGF, and GDNF. 展开更多
关键词 glial cell line-derived neurotrophic factor Nerve Growth factor Peripheral Nerve Safflower Extract andAceglutamide Injection Vascular Endothelial Growth factor
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嗅鞘细胞-胶质细胞源性神经营养因子基因工程细胞移植对坐骨神经再生的作用 被引量:12
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作者 马玉海 张勇 +3 位作者 曹莉 张少成 侯铁胜 何成 《中华实验外科杂志》 CAS CSCD 北大核心 2004年第1期17-19,共3页
目的 研究胶质细胞源性神经营养因子 (GDNF)基因修饰的嗅鞘细胞 (OECs)移植对周围神经再生的作用。方法 将 40只SD大鼠随机分为 4组 ,每组 10只 ,切除 3mm右侧坐骨神经并用硅胶管套接修复 ,管内分别给予生理盐水、体外培养纯化的OECs... 目的 研究胶质细胞源性神经营养因子 (GDNF)基因修饰的嗅鞘细胞 (OECs)移植对周围神经再生的作用。方法 将 40只SD大鼠随机分为 4组 ,每组 10只 ,切除 3mm右侧坐骨神经并用硅胶管套接修复 ,管内分别给予生理盐水、体外培养纯化的OECs、GDNF和OECs GDNF基因工程细胞 ,术后 6周 ,分别行电生理、组织学检查和辣根过氧化物酶 (HRP)逆行示踪 ,观察各种处理对神经元存活和纤维再生的影响。结果 术后 6周 ,各组修复神经均有不同程度再生。电生理及组织化学结果显示治疗组优于对照组 ,差异有显著性。结论 OECs GDNF移植能促进周围神经再生 ,且效果优于单纯OECs或GDNF移植。 展开更多
关键词 嗅鞘细胞 胶质细胞源性神经营养因子 基因工程 细胞移植 坐骨神经再生
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Neuroprotective Effects of Electroacupuncture on Hypoxic-Ischemic Encephalopathy in Newborn Rats Are Associated with Increased Expression of GDNF-RET and Protein Kinase B 被引量:11
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作者 徐涛 许能贵 +3 位作者 杨忠华 万言珍 吴清龙 黄康柏 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2016年第6期457-466,共10页
Objective: To explore the neuroprotective effects of electroacupuncture (EA) on hypoxic-ischemic encephalopathy (HIE) and to further investigate the role of glial cell line-derived neurotrophic factor (GDNF) fa... Objective: To explore the neuroprotective effects of electroacupuncture (EA) on hypoxic-ischemic encephalopathy (HIE) and to further investigate the role of glial cell line-derived neurotrophic factor (GDNF) family receptor member RET (rearranged during transfection) and its key downstream phosphatidylinositol 3 kinase (PI-3K)/protein kinase B (Akt) pathway in the process. Methods: A total of 220 seven-day-old SD rats (of either sex, from 22 broods) were randomly divided into two groups, one (30 rats) for sham-surgery group and the other (190 rats) for HIE model group. The HIE model was established using the left common carotid artery ligation method in combination with hypoxic treatment. The successfully established rats were randomly divided into five groups, including control model group, EA group, sham-EA group, antagonist group and antagonist plus electroacupuncture group, with 35 rats in each group. Baihui (GV 20), Dazhui (GV 14), Quchi (LI 11) and Yongquan (KI 1) acupoints were chosen for acupuncture. EA was performed at Baihui and Quchi for 10 min once a day for continuous 1, 3, 7 and 21 days, respectively. The rats were then killed after the operation and injured cerebral cortex was taken for the measurement of neurologic damage by hematoxylin-eosin (HE) staining and the degenerative changes of cortical ultrastructure by transmission electron microscopy. RET mRNA level and Akt protein level were detected by real-time reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively. Results: EA could ameliorate neurologic damage of the first somatic sensory area (SITr) and alleviate the degenerative changes of ultrastructure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein l 展开更多
关键词 hypoxic-ischemic encephalopathy ELECTROACUPUNCTURE glial cell line-derived neurotrophic factor rearranged during transfection protein kinase B
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灵芝孢子粉对戊四氮致痫大鼠脑组织GDNF与NT-3表达的影响 被引量:11
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作者 赵璐 王淑秋 王喆 《中国病理生理杂志》 CAS CSCD 北大核心 2010年第4期812-815,共4页
目的:观察和探讨灵芝孢子粉干预后戊四氮(PTZ)致痫大鼠皮质和海马区胶质细胞源性神经营养因子(GDNF)和神经营养因子-3(NT-3)的变化,进一步研究癫痫的发病机制及灵芝孢子粉的作用机制。方法:Wistar大鼠30只,随机分为正常对照组、癫痫模... 目的:观察和探讨灵芝孢子粉干预后戊四氮(PTZ)致痫大鼠皮质和海马区胶质细胞源性神经营养因子(GDNF)和神经营养因子-3(NT-3)的变化,进一步研究癫痫的发病机制及灵芝孢子粉的作用机制。方法:Wistar大鼠30只,随机分为正常对照组、癫痫模型组和灵芝孢子粉治疗组,每组10只。模型组和治疗组采用PTZ腹腔注射制作Wistar大鼠慢性点燃模型。实验后断头迅速取脑,采用免疫组化方法检测皮质和海马区GDNF和NT-3表达的变化;同时用Westernblotting检测海马各指标蛋白的变化。结果:灵芝孢子粉干预后,免疫组化显示:皮质和海马区GDNF和NT-3较癫痫模型组明显增加;Western blotting检测显示:海马中GDNF和NT-3表达较癫痫组显著增加。结论:灵芝孢子粉能够增强GDNF和NT-3的表达从而减轻癫痫发作给神经系统带来的损伤,所以灵芝孢子粉可能具有减轻痫性发作、保护神经元的作用。 展开更多
关键词 癫痫 戊四氮 胶质细胞源性神经营养因子 神经营养因子3 灵芝孢子粉
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Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction 被引量:9
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作者 Jing Liu Xiaofeng Wang +3 位作者 Ying Liu Na Yang Jing Xu Xiaotun Ren 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第23期2190-2197,共8页
From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg taurine was daily added ... From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg taurine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neo- natal rats with intrauterine growth restriction undergoing taurine supplement were obtained for fur- ther experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. Immu- nohistochemical staining revealed that taurine supplement increased glial cell line-derived neuro- trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain. 展开更多
关键词 neural regeneration intrauterine growth restriction fetal rats brain neural cells TAURINE cell apop-tosis glial cell line-derived neurotrophic factor caspase-3 neural development grants-supportedpaper NEUROREGENERATION
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Transplantation of neural stem cells overexpressing glial cell line-derived neurotrophic factor enhances Akt and Erkl/2 signaling and neurogenesis in rats after stroke 被引量:9
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作者 YUAN Miao WEN Sheng-jun +5 位作者 YANG Chao-xian PANG Yuan-guang GAO Xiao-qing LIU Xiao-qing HUANG Liang YUAN Qiong-lan 《Chinese Medical Journal》 SCIE CAS CSCD 2013年第7期1302-1309,共8页
Background Our previous studies have indicated that the beneficial effects of grafting neural stem cells (NSCs) overexpressing glial cell line-derived neurotrophic factor (GDNF) in rats after stroke. However, the ... Background Our previous studies have indicated that the beneficial effects of grafting neural stem cells (NSCs) overexpressing glial cell line-derived neurotrophic factor (GDNF) in rats after stroke. However, the underlying mechanisms are highly debatable. In this study, we investigated whether neurogenesis, Akt, and extracellular signal- regulated kinase 1/2 (Erkl/2) signaling were involved in this process. Methods Transient ischemic stroke were induced by occluding middle cerebral artery for 2 hours and reperfusion. At 3 days after reperfusion, GDNF/NSCs, NSCs, and vehicle were administered. Immunohistochemical staining was used to evaluate neurogenesis by nestin antibody; phosphorylation of Akt and Erkl/2 was investigated by Western blotting analysis. Results Transplantation of GDNF/NSCs and NSCs significantly increased nestin-positive cells compared to control group (vehicle) from 1 to 7 weeks after reperfusion, and GDNF/NSCs showed stronger effect than NSCs at 2 and 3 weeks after reperfusion. Meanwhile, enhanced phosphorylation level of Erkl/2 was observed in the GDNF/NSCs and NSCs groups compared with control group, and phosphorylation level of Erkl/2 in GDNF/NSCs group was remarkably higher than that of NSCs group at any given time. In contrast, expression of mitogen-activated protein kinase phosphatase-1 (MKP-1), known as inhibitor of Erkl/2 signaling, was significantly decreased in the GDNF/NSCs and NSCs groups compared with the control group. Moreover, much enhanced and prolonged phosphorylation level of Akt of GDNF/NSCs group was detected compared with control and NSCs group. Conclusion Grafting GDNF/NSCs enhances neurogenesis and activates Akt and Erkl/2 signaling, that may provide the potential for GDNF/NSCs in stroke treatment. 展开更多
关键词 glial cell line-derived neurotrophic factor neural stem cells TRANSPLANTATION NEUROGENESIS 4kt and Erkl/2 signaling
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重度颅脑损伤后GDNF表达的实验研究 被引量:7
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作者 王欣 廖志钢 +3 位作者 刘敏 张林 易旭夫 胡华子 《法医学杂志》 CAS CSCD 2003年第1期1-3,共3页
目的观察重度颅脑损伤后GDNF的表达变化规律。 方法应用免疫组织化学方法和图像分析技术,对大鼠重度颅脑损伤后不同时间大脑皮层、丘脑和脑干等几个脑区内GDNF的表达变化进行研究。结果CDNF在脑损伤后1d表达开始增高,3d达表达最高峰,5d... 目的观察重度颅脑损伤后GDNF的表达变化规律。 方法应用免疫组织化学方法和图像分析技术,对大鼠重度颅脑损伤后不同时间大脑皮层、丘脑和脑干等几个脑区内GDNF的表达变化进行研究。结果CDNF在脑损伤后1d表达开始增高,3d达表达最高峰,5d时回落不明显,7d有所回落,但仍高于正常水平。结论GDNF在脑损伤后的时序性变化规律使其有可能成为一种脑损伤时间推断的客观指标。 展开更多
关键词 重度颅脑损伤 胶质细胞源性神经营养因子 实验研究 时间推断 法医学 免疫组织化学
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丹参注射液对急性脊髓损伤大鼠脊髓灰质GDNF mRNA的提高作用及其机制 被引量:9
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作者 韦理 张俐 《中国中西医结合杂志》 CAS CSCD 北大核心 2013年第7期933-937,共5页
目的观察丹参注射液对急性脊髓损伤(spinal cord injury,SCI)大鼠的脊髓灰质胶源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)的作用,并探讨其机制。方法将144只SD雄性大鼠制作成SCI模型,随机分为治疗组、对照组... 目的观察丹参注射液对急性脊髓损伤(spinal cord injury,SCI)大鼠的脊髓灰质胶源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)的作用,并探讨其机制。方法将144只SD雄性大鼠制作成SCI模型,随机分为治疗组、对照组及SCI组(每组各48只),其中治疗组给予腹腔注射丹参注射液[1.78mL/(kg·天)],对照组腹腔注射大剂量甲基强地松龙[30mg/(kg·23h),45min后按5.4mg/(kg·h)计算23h总量,分4次注射],SCI组不予干预,此外另选48只SD雄性大鼠为假手术组(不损伤脊髓),进行伤后1、3、7及14天各组脊髓运动功能评估,检测以上时间点脊髓灰质GDNF mRNA表达。结果本实验造模成功率80.54%,脊髓损伤后14天内,治疗组出血、水肿以及神经元坏死等表现明显少于SCI组,与对照组没有明显区别。SCI组损伤后1、3、7、14天斜板试验临界角均低于假手术组同期(P<0.01),GDNF mRNA阳性产物吸光度值高于假手术组同期(P<0.01);损伤后1天,治疗组斜板试验临界角低于治疗前(P<0.01),治疗组斜板试验临界角及GDNF mRNA阳性产物吸光度值低于对照组同期(P<0.05),高于SCI组同期(P<0.01);损伤后3天,治疗组GDNF mRNA阳性产物吸光度值高于损伤后1天及SCI组同期(P<0.01,P<0.05),低于对照组同期(P<0.05);损伤后7天,治疗组斜板试验临界角高于损伤后3天及SCI组同期(P<0.01),低于对照组(P<0.05),治疗组GDNF mRNA阳性产物吸光度值高于SCI组同期(P<0.01);损伤后14天,治疗组斜板试验临界角高于损伤后7天(P<0.01,P<0.05),治疗组斜板试验临界角高及GDNF mRNA阳性产物吸光度值高于SCI组同期(P<0.01)。结论丹参能减轻大鼠损伤脊髓的水肿、出血,改善脊髓微循环,从而提高SCI鼠脊髓灰质GDNF mRNA,是SCI早期理想的治疗药物。 展开更多
关键词 丹参注射液 急性脊髓损伤 胶源性神经营养因子
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胶质细胞源神经营养因子在大鼠骨髓间充质干细胞神经分化中的表达 被引量:8
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作者 吴晓娟 魏明发 +4 位作者 柴成伟 高贺云 黎润光 冯杰雄 邓科 《实用儿科临床杂志》 CAS CSCD 北大核心 2009年第23期1806-1808,共3页
目的探讨大鼠骨髓间充质干细胞(BMSCs)神经分化及胶质细胞源神经营养因子(GDNF)表达的变化。方法体外培养大鼠BMSCs,传至第4代,行神经诱导分化。流式细胞术检测培养细胞表面的骨髓基质细胞标志CD90和造血细胞标志CD45。以10μg/L碱性成... 目的探讨大鼠骨髓间充质干细胞(BMSCs)神经分化及胶质细胞源神经营养因子(GDNF)表达的变化。方法体外培养大鼠BMSCs,传至第4代,行神经诱导分化。流式细胞术检测培养细胞表面的骨髓基质细胞标志CD90和造血细胞标志CD45。以10μg/L碱性成纤维细胞生长因子(bFGF)和(或)10μg/L表皮生长因子(EGF)在含100mL/L胎牛血清(FBS)的DMEM培养基中诱导,7d后观察其细胞形态变化,免疫组织化学法检测其胶质纤维酸性蛋白(GFAP)及神经元特异性烯醇化酶(NSE)的表达,RT-PCR检测其GDNF及其受体RETmRNA的变化。结果BMSCs能在体外成功培养及纯化,第4代细胞高表达CD90(93.4%),不表达CD45。诱导7d后,实验组大鼠均可见GFAP及NSE表达,而对照组为阴性。实验组中bFGF组及bFGF加EGF组表达的NSE高于EGF组,而EGF组表达GFAP更高。RT-PCR检测示BMSCs向神经细胞诱导后,GDNF表达显著增强,并促使RET基因表达,以bFGF加EGF组最明显。结论bFGF及EGF可促进大鼠BMSCs向神经细胞分化,在向神经细胞分化的过程中,能促进GDNF和RET基因的表达,GDNF可能在BMSCs向神经细胞分化过程中起重要作用。 展开更多
关键词 骨髓间充质干细胞 胶质细胞源神经营养因子 神经细胞 大鼠
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下瘀血汤抑制胶质细胞源性神经营养因子抗肝纤维化的作用机制 被引量:9
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作者 张玮 杨广越 +5 位作者 沈东晓 马文婷 陶乐 吴柳 严萍 刘成 《临床肝胆病杂志》 CAS 北大核心 2021年第3期575-581,共7页
目的探讨下瘀血汤是否通过抑制胶质细胞源性神经营养因子(GDNF)发挥抗肝纤维化的作用。方法24只C57BL/6小鼠随机分为对照组、模型组、下瘀血汤组,每组各8只。模型组和下瘀血汤小鼠腹腔注射10%CCl4,第4周开始下瘀血汤组小鼠给予0.4678 g... 目的探讨下瘀血汤是否通过抑制胶质细胞源性神经营养因子(GDNF)发挥抗肝纤维化的作用。方法24只C57BL/6小鼠随机分为对照组、模型组、下瘀血汤组,每组各8只。模型组和下瘀血汤小鼠腹腔注射10%CCl4,第4周开始下瘀血汤组小鼠给予0.4678 g/kg下瘀血汤灌胃。检测肝功能指标ALT、AST水平,观测肝脏组织病理形态学。免疫组化检测平滑肌肌动蛋白(α-SMA)及GDNF蛋白表达。GDNF(10 ng/ml)处理GFP-Col-HSC和人原代肝星状细胞(HSC),检测HSC活化。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果模型组ALT和AST水平较对照组显著升高,下瘀血汤组ALT和AST水平较模型组显著降低(P值均<0.01)。肝组织病理学显示,模型组炎症细胞浸润明显,增生的胶原纤维形成纤维间隔,下瘀血汤组胶原纤维间隔较疏松及炎症细胞浸润减轻。免疫组化显示,与对照组相比,模型组α-SMA及GDNF阳性表达显著升高(P值均<0.01),均分布在纤维间隔,下瘀血汤组α-SMA与GDNF表达较模型组均显著降低(P值均<0.05)。免疫印迹结果显示,对照小鼠肝组织GDNF表达比较低,CCl4造模6周肝纤维化形成,GDNF表达上调10倍左右,下瘀血汤显著抑制模型小鼠GDNF蛋白表达(P值均<0.01);α-SMA和Ⅰ型胶原α1(Col1)表达在肝纤维化模型小鼠显著上调,下瘀血汤处理后α-SMA与Col1显著下降(P值均<0.01)。体外结果显示,GDNF可诱导HSC细胞α-SMA及Ⅰ型胶原α1蛋白表达显著上调,而下瘀血汤对此有显著抑制作用(P值均<0.01)。结论肝纤维化形成中GDNF表达显著上调,GDNF可诱导HSC活化,下瘀血汤可抑制GDNF从而抗肝纤维化。 展开更多
关键词 肝硬化 下瘀血汤 胶质细胞源性神经营养因子
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