As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed ex- tract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for isch...As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed ex- tract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for ischemic stroke patients. L-3-n-butylphthalide possesses significant efficacy in the treatment of acute ischemic stroke. The activated Akt kinase pathway can prevent the death of nerve cells and exhibit neuroprotective effects in the brain after stroke. This study provides the hypothesis that I-3-n- butylphthalide has a certain therapeutic effect on vascular dementia, and its mechanism depends on the activation of the Akt kinase pathway. A vascular dementia mouse model was established by cere- bral repetitive ischemia/reperfusion, and intragastrically administered I-3-n-butylphthalide daily for 28 consecutive days after ischemia/repedusion, or 7 consecutive days before ischemia/reperfusion. The Morris water maze test showed significant impairment of spatial learning and memory at 4 weeks after operation, but intragastric administration of I-3-n-butylphthalide, especially pretreatment with I-3-n- butylphthalide, significantly reversed these changes. Thionine staining and western blot analylsis showed that preventive and therapeutic application of I-3-n-butylphthalide can reduce loss of pyrami- dal neurons in the hippocampal CA1 region and alleviate nerve damage in mice with vascular demen- tia. In addition, phosphorylated Akt expression in hippocampal tissue increased significantly after I-3-n- butylphthalide treatment. Experimental findings demonstrate that I-3-n-butylphthalide has preventive and therapeutic effects on vascular dementia, and its mechanism may be mediated by upregulation of phosphorylated Akt in the hippocampus.展开更多
BACKGROUND：Noxa, a pro-apoptotic member of the Bcl-2 protein family, has been shown to induce the mitochondrial pathway of apoptosis and to mediate hypoxic cell death in a rat model of cerebral ischemia. This suggest...BACKGROUND：Noxa, a pro-apoptotic member of the Bcl-2 protein family, has been shown to induce the mitochondrial pathway of apoptosis and to mediate hypoxic cell death in a rat model of cerebral ischemia. This suggests that Noxa could participate in apoptosis during vascular dementia （VD）. OBJECTIVE： To detect Noxa and caspase-3 expression after electro-acupuncture in VD rats to further validate the mechanism of electro-acupuncture-induced effects in the treatment of VD. DESIGN, TIME AND SETTING： A randomized, controlled study was performed at the Center for the Neurobiology of Fujian Medical University between January 2006 and March 2007. MATERIALS： A total of forty adult, male, Sprague Dawley rats were included in this study. The following equipment was used： confocal laser scanning microscope （Sp5, Leica, Germany）, water maze （Bejing Suntendy Science and Technology Co., Ltd., China）, and SDZ-II electronic acupuncture treatment instruments （Suzhou Medical Appliance Factory, China）. METHODS： Thirty-eight rats with sufficient learning and memory abilities were selected by Morris water maze criteria. Twelve rats received sham-surgery; the remaining 26 rats were used to establish a VD model by bilateral occlusion of the common carotid arteries. The rats that survived the occlusion procedure were randomly assigned into an electro-acupuncture group （n = 11） and a VD model group （n = 12）. MAIN OUTCOME MEASURES： Neuropathological changes were observed with hematoxylin-eosin staining of the hippocampus and expression of Noxa and caspase-3 in the hippocampal CA1 region was analyzed by confocal laser scanning microscope following immunofluorescence staining. RESULTS： Expressions of Noxa and caspase-3 in the electro-acupuncture group and sham-operated group were less than in the VD model group （P 〈 0.01）. Electro-acupuncture reduced the amount of apoptotic neurons in hippocampal CA1 area of rats with VD. The average latency in the Morris water maze test was significantly shorter, and escape strategies improved from edge and random searches to more linear swim pathways in the electro-acupuncture group compared with the VD model group （P 〈 0.01）. CONCLUSION： Electro-acupuncture can improve learning and memory ability and inhibit the occurrence of apoptosis by blocking expression of Noxa and caspase-3 in the hippocampal CA1 region of VD rats.展开更多
目的 观察针刺对血管性痴呆(vascular dementia,Va D)大鼠学习记忆能力及半胱天冬酶(cysteinyl aspartate specific proteinase,Caspase)-3通路相关蛋白的影响及其机制研究,探索针刺防治Va D的新靶点。方法 健康雄性SD大鼠随机分为假手...目的 观察针刺对血管性痴呆(vascular dementia,Va D)大鼠学习记忆能力及半胱天冬酶(cysteinyl aspartate specific proteinase,Caspase)-3通路相关蛋白的影响及其机制研究,探索针刺防治Va D的新靶点。方法 健康雄性SD大鼠随机分为假手术组、模型组和针刺组,模型组和针刺组大鼠制备Va D模型,针刺组选取百会和双侧肾俞、丰隆进行针刺干预2周,假手术组和模型组不予其他干预。观察各组大鼠的行为学、海马CA1区形态学改变,检测B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)、Caspase-3、Bcl-2相关X蛋白(Bcl-2-associated X protein,Bax) m RNA及蛋白的表达。结果 与假手术组比较,模型组大鼠逃避潜伏期明显延长(P<0.01),穿越平台次数显著减少(P<0.01),大鼠海马组织内Bax、Caspase-3 m RNA及蛋白的表达明显增加(P<0.01),Bcl-2 m RNA及蛋白的表达明显下降(P<0.01)。与模型组比较,针刺组大鼠逃避潜伏期明显缩短(P<0.01),穿越平台次数明显增加(P<0.01),大鼠海马区Bax、Caspase-3 m RNA及蛋白表达明显下降(P<0.01),Bcl-2 m RNA及蛋白水平明显增加(P<0.01)。结论 针刺能提高Va D大鼠的学习记忆能力,其机制可能与调节Caspase-3通路相关蛋白表达、抑制神经元凋亡相关。展开更多
Aim: To compare serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metallo-proteinase 1 (TIMP1) in vascular dementia patients and healthy control subjects. Methods: A case control study was carried ...Aim: To compare serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metallo-proteinase 1 (TIMP1) in vascular dementia patients and healthy control subjects. Methods: A case control study was carried out in Ain Shams University hospital, Cairo, Egypt. 32 cases with vascular dementia were collected and classified into 2 subgroups;vascular dementia of multiinfarct type (VDMI) 14 patients, and vascular dementia of subcortical type (VDSC) 18 subjects. 23 cases with normal cognitive functions were collected as control group. Cases were subjected to comprehensive geriatric assessment, neurological examination, neuropsychological testing and brain CT scan. Blood sample was collected to analyze serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metalloproteinase 1 (TIMP1). Results: Mean serum level of TIMP1 (20.85 × 103 picogram/ml) was significantly lower than mean serum level of TIMP1 in control group (27.69 × 103 picogram/ml) (p = 0.018). The same finding was also evident when comparing VDMI subgroup mean serum TIMP1 (18.71 × 103 pc/ml) to control group (p = 0.025). There was no significant difference between mean serum MMP3 levels in cases group (mean = 67.39 × 103) as compared to control group (mean = 61.65 × 103 pc/ml) (p = 0.519). Conclusion: Patients with VD particularly VDMI has lower serum level of TIMP1 as compared to control group.展开更多
It remains unclear whether autophagy affects hippocampal neuronal injury in vascular dementia. In the present study, we investigated the effects of autophagy blockade on hippocampal neuro- nal injury in a rat model of...It remains unclear whether autophagy affects hippocampal neuronal injury in vascular dementia. In the present study, we investigated the effects of autophagy blockade on hippocampal neuro- nal injury in a rat model of vascular dementia. In model rats, hippocampal CA1 neurons were severely damaged, and expression of the autophagy-related proteins beclin-1, cathepsin B and microtubule-associated protein 1 light chain 3 was elevated compared with that in sham-operated animals. These responses were suppressed in animals that received a single intraperitoneal injection of wortmannin, an autophagy inhibitor, prior to model establishment. The present results confirm that autophagy and autophagy-related proteins are involved in the pathological changes of vascular dementia, and that inhibition of autophagy has neuroprotective effects.展开更多
目的探讨核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）对痴呆发病的影响。方法 2014年1月~2015年10月,用RT-PCR方法检测16例阿尔茨海默病（AD）患者、22例血管性痴呆（VD）患者和20名年龄相似的健康体检者外周血单个核细胞中NLRP3 m RN...目的探讨核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）对痴呆发病的影响。方法 2014年1月~2015年10月,用RT-PCR方法检测16例阿尔茨海默病（AD）患者、22例血管性痴呆（VD）患者和20名年龄相似的健康体检者外周血单个核细胞中NLRP3 m RNA水平;ELISA法检测血清中白细胞介素（IL）-1β和IL-18蛋白水平;收集患者外周血白细胞计数（WBC）和血清总钙浓度等临床检测资料;将NLRP3 m RNA水平分别与IL-1β、IL-18、WBC和钙浓度进行单因素相关分析。结果 NLRP3 m RNA水平由高到低依次为AD组〉VD组〉健康组（q〉11.48,P〈0.05）;IL-1β水平AD组高于健康组（q=16.74,P〈0.05）,AD组与VD组、VD组与健康组无显著性差异（P〉0.05）;IL-18水平各组间均无显著性差异（P〉0.05）。AD组中,NLRP3 m RNA水平与IL-1β水平（r=0.64）、血清钙水平（r=0.58）呈正相关,与IL-18、WBC无相关性（P〉0.05）。结论 NLRP3炎症小体中相关蛋白或基因表达与AD的发病可能有较大关系,与VD的发病关系不大。展开更多
基金supported by the National Natural Science Foundationof China, No. 81241037the Natural Science Foundationof Hebei Province, No.H2013307046
文摘As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed ex- tract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for ischemic stroke patients. L-3-n-butylphthalide possesses significant efficacy in the treatment of acute ischemic stroke. The activated Akt kinase pathway can prevent the death of nerve cells and exhibit neuroprotective effects in the brain after stroke. This study provides the hypothesis that I-3-n- butylphthalide has a certain therapeutic effect on vascular dementia, and its mechanism depends on the activation of the Akt kinase pathway. A vascular dementia mouse model was established by cere- bral repetitive ischemia/reperfusion, and intragastrically administered I-3-n-butylphthalide daily for 28 consecutive days after ischemia/repedusion, or 7 consecutive days before ischemia/reperfusion. The Morris water maze test showed significant impairment of spatial learning and memory at 4 weeks after operation, but intragastric administration of I-3-n-butylphthalide, especially pretreatment with I-3-n- butylphthalide, significantly reversed these changes. Thionine staining and western blot analylsis showed that preventive and therapeutic application of I-3-n-butylphthalide can reduce loss of pyrami- dal neurons in the hippocampal CA1 region and alleviate nerve damage in mice with vascular demen- tia. In addition, phosphorylated Akt expression in hippocampal tissue increased significantly after I-3-n- butylphthalide treatment. Experimental findings demonstrate that I-3-n-butylphthalide has preventive and therapeutic effects on vascular dementia, and its mechanism may be mediated by upregulation of phosphorylated Akt in the hippocampus.
基金Fund for Youth Teachers from Fujian Provincial Health Department, No. 2005-2-40
文摘BACKGROUND：Noxa, a pro-apoptotic member of the Bcl-2 protein family, has been shown to induce the mitochondrial pathway of apoptosis and to mediate hypoxic cell death in a rat model of cerebral ischemia. This suggests that Noxa could participate in apoptosis during vascular dementia （VD）. OBJECTIVE： To detect Noxa and caspase-3 expression after electro-acupuncture in VD rats to further validate the mechanism of electro-acupuncture-induced effects in the treatment of VD. DESIGN, TIME AND SETTING： A randomized, controlled study was performed at the Center for the Neurobiology of Fujian Medical University between January 2006 and March 2007. MATERIALS： A total of forty adult, male, Sprague Dawley rats were included in this study. The following equipment was used： confocal laser scanning microscope （Sp5, Leica, Germany）, water maze （Bejing Suntendy Science and Technology Co., Ltd., China）, and SDZ-II electronic acupuncture treatment instruments （Suzhou Medical Appliance Factory, China）. METHODS： Thirty-eight rats with sufficient learning and memory abilities were selected by Morris water maze criteria. Twelve rats received sham-surgery; the remaining 26 rats were used to establish a VD model by bilateral occlusion of the common carotid arteries. The rats that survived the occlusion procedure were randomly assigned into an electro-acupuncture group （n = 11） and a VD model group （n = 12）. MAIN OUTCOME MEASURES： Neuropathological changes were observed with hematoxylin-eosin staining of the hippocampus and expression of Noxa and caspase-3 in the hippocampal CA1 region was analyzed by confocal laser scanning microscope following immunofluorescence staining. RESULTS： Expressions of Noxa and caspase-3 in the electro-acupuncture group and sham-operated group were less than in the VD model group （P 〈 0.01）. Electro-acupuncture reduced the amount of apoptotic neurons in hippocampal CA1 area of rats with VD. The average latency in the Morris water maze test was significantly shorter, and escape strategies improved from edge and random searches to more linear swim pathways in the electro-acupuncture group compared with the VD model group （P 〈 0.01）. CONCLUSION： Electro-acupuncture can improve learning and memory ability and inhibit the occurrence of apoptosis by blocking expression of Noxa and caspase-3 in the hippocampal CA1 region of VD rats.
文摘目的 观察针刺对血管性痴呆(vascular dementia,Va D)大鼠学习记忆能力及半胱天冬酶(cysteinyl aspartate specific proteinase,Caspase)-3通路相关蛋白的影响及其机制研究,探索针刺防治Va D的新靶点。方法 健康雄性SD大鼠随机分为假手术组、模型组和针刺组,模型组和针刺组大鼠制备Va D模型,针刺组选取百会和双侧肾俞、丰隆进行针刺干预2周,假手术组和模型组不予其他干预。观察各组大鼠的行为学、海马CA1区形态学改变,检测B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)、Caspase-3、Bcl-2相关X蛋白(Bcl-2-associated X protein,Bax) m RNA及蛋白的表达。结果 与假手术组比较,模型组大鼠逃避潜伏期明显延长(P<0.01),穿越平台次数显著减少(P<0.01),大鼠海马组织内Bax、Caspase-3 m RNA及蛋白的表达明显增加(P<0.01),Bcl-2 m RNA及蛋白的表达明显下降(P<0.01)。与模型组比较,针刺组大鼠逃避潜伏期明显缩短(P<0.01),穿越平台次数明显增加(P<0.01),大鼠海马区Bax、Caspase-3 m RNA及蛋白表达明显下降(P<0.01),Bcl-2 m RNA及蛋白水平明显增加(P<0.01)。结论 针刺能提高Va D大鼠的学习记忆能力,其机制可能与调节Caspase-3通路相关蛋白表达、抑制神经元凋亡相关。
文摘Aim: To compare serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metallo-proteinase 1 (TIMP1) in vascular dementia patients and healthy control subjects. Methods: A case control study was carried out in Ain Shams University hospital, Cairo, Egypt. 32 cases with vascular dementia were collected and classified into 2 subgroups;vascular dementia of multiinfarct type (VDMI) 14 patients, and vascular dementia of subcortical type (VDSC) 18 subjects. 23 cases with normal cognitive functions were collected as control group. Cases were subjected to comprehensive geriatric assessment, neurological examination, neuropsychological testing and brain CT scan. Blood sample was collected to analyze serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metalloproteinase 1 (TIMP1). Results: Mean serum level of TIMP1 (20.85 × 103 picogram/ml) was significantly lower than mean serum level of TIMP1 in control group (27.69 × 103 picogram/ml) (p = 0.018). The same finding was also evident when comparing VDMI subgroup mean serum TIMP1 (18.71 × 103 pc/ml) to control group (p = 0.025). There was no significant difference between mean serum MMP3 levels in cases group (mean = 67.39 × 103) as compared to control group (mean = 61.65 × 103 pc/ml) (p = 0.519). Conclusion: Patients with VD particularly VDMI has lower serum level of TIMP1 as compared to control group.
基金supported by the Scientific Technology Research Project of Hebei Provincial Higher Learning Schools in China,No.ZH2012046the Major Medical Research Program of Hebei Province in China,No.ZD2013087
文摘It remains unclear whether autophagy affects hippocampal neuronal injury in vascular dementia. In the present study, we investigated the effects of autophagy blockade on hippocampal neuro- nal injury in a rat model of vascular dementia. In model rats, hippocampal CA1 neurons were severely damaged, and expression of the autophagy-related proteins beclin-1, cathepsin B and microtubule-associated protein 1 light chain 3 was elevated compared with that in sham-operated animals. These responses were suppressed in animals that received a single intraperitoneal injection of wortmannin, an autophagy inhibitor, prior to model establishment. The present results confirm that autophagy and autophagy-related proteins are involved in the pathological changes of vascular dementia, and that inhibition of autophagy has neuroprotective effects.
文摘目的探讨核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）对痴呆发病的影响。方法 2014年1月~2015年10月,用RT-PCR方法检测16例阿尔茨海默病（AD）患者、22例血管性痴呆（VD）患者和20名年龄相似的健康体检者外周血单个核细胞中NLRP3 m RNA水平;ELISA法检测血清中白细胞介素（IL）-1β和IL-18蛋白水平;收集患者外周血白细胞计数（WBC）和血清总钙浓度等临床检测资料;将NLRP3 m RNA水平分别与IL-1β、IL-18、WBC和钙浓度进行单因素相关分析。结果 NLRP3 m RNA水平由高到低依次为AD组〉VD组〉健康组（q〉11.48,P〈0.05）;IL-1β水平AD组高于健康组（q=16.74,P〈0.05）,AD组与VD组、VD组与健康组无显著性差异（P〉0.05）;IL-18水平各组间均无显著性差异（P〉0.05）。AD组中,NLRP3 m RNA水平与IL-1β水平（r=0.64）、血清钙水平（r=0.58）呈正相关,与IL-18、WBC无相关性（P〉0.05）。结论 NLRP3炎症小体中相关蛋白或基因表达与AD的发病可能有较大关系,与VD的发病关系不大。
