目的观察异丙酚预处理对拟阿尔茨海默病(AD)大鼠海马CA1区胆碱乙酰转移酶(cho- line acetyl-transferase,ChAT)表达的影响,分析异丙酚的脑保护作用。方法30只健康雄性SD大鼠随机分为对照组、拟AD模型组(简称模型组)和异丙酚预处理组(简...目的观察异丙酚预处理对拟阿尔茨海默病(AD)大鼠海马CA1区胆碱乙酰转移酶(cho- line acetyl-transferase,ChAT)表达的影响,分析异丙酚的脑保护作用。方法30只健康雄性SD大鼠随机分为对照组、拟AD模型组(简称模型组)和异丙酚预处理组(简称异丙酚组)。模型组、异丙酚预处理组在大鼠海马CA1区微量注射冈田酸(Okadaic acid,OA),建立拟AD大鼠模型。异丙酚预处理组大鼠于拟AD模型制作前30 min,腹腔注射异丙酚100 mg/kg。然后用免疫组化方法观察大鼠海马CA1区ChAT的表达。结果30只大鼠顺利完成全部实验的有27只,模型组和异丙酚预处理组有2只大鼠死亡、1只出现偏瘫无法进行余下实验,这可能与动物的个体差异不能耐受实验有关。随机取27只大鼠作为结果分析样本(每组9只)。①模型组与对照组大鼠相比:海马CA1区ChAT免疫组化阳性表达明显减少(P<0.05);②异丙酚预处理组与模型组大鼠相比:海马CA1区ChAT免疫组化阳性表达明显增多(P<0.05)。结论拟AD模型建立前30 min异丙酚预处理能增强ChAT的表达,有明显的脑保护作用。展开更多
Objective：To observe the therapeutic effect of Yangxue Qingnao Granule（养血清脑颗粒, YXQNG） on cognitive impairment induced by chronic cerebral hypoperfusion and to investigate its impact on oxidative stress,apopto...Objective：To observe the therapeutic effect of Yangxue Qingnao Granule（养血清脑颗粒, YXQNG） on cognitive impairment induced by chronic cerebral hypoperfusion and to investigate its impact on oxidative stress,apoptosis,and the cholinergic system.Methods：Adult male Wistar rats were subjected to chronic cerebral hypoperfusion by permanent occlusion of bilateral common carotid arteries（2-VO）.Thirty rats were randomly assigned to one of the five treatment groups in a 1：1：1：1：1 ratio：sham operation plus normal saline treatment,2-VO plus normal saline treatment,2-VO plus YXQNG at a dose of 2 g·kg（-1）·d^（-1） or 4 g·kg（-1）·d^（-1）, or 2-VO plus rivastigmine 2 mgkg^（-1）·d^（-1）.The Morris water maze test was used to assess the spatial memory retrieval.Apoptosis,total antioxide capacity（T-AOC）,acetylcholine esterase（AchE） and choline acetyl transferase（ChAT） activities in the hippocampus and the cortex were investigated.Results：In the chronic cerebral hypoperfusion model,the 2-VO plus saline treatment resulted in impaired special learning as shown by the significantly prolonged escape latency and shorter swim time in the first quadrant as compared to the sham operation.The impairment was associated with apoptosis and significant decreases in T-AOC,AchE and ChAT activities in the hippocampus and the cortex.Treatment with YXQNG at either 2 g·kg（-1）·d^（-1） or 4 g·kg（-1）·d^（-1） dose,or rivastigmine resulted in significantly shorter escape latencies and longer swim time in the first quadrant.YXQNG at both doses,but not rivastigmine,had significant reduction in apoptosis,and significant increases in T-AOC and ChAT activity in both the hippocampus and the cortex.Unlike rivastigmine,neither dose of YXQNG showed significant reduction in AchE activity.Conclusions：YXQNG ameliorated cognitive impairment induced by chronic cerebral hypoperfusion.The protective effect may be mediated through its regulation of apoptosis and activities of T-AOC and C展开更多
BACKGROUND： To date, no drugs are able to halt the progression of Alzheimer＇s disease （AD）. Neural stem cells （NSCs） transplantation has been widely used to treat AD, but the mechanism of AD treatment remains un...BACKGROUND： To date, no drugs are able to halt the progression of Alzheimer＇s disease （AD）. Neural stem cells （NSCs） transplantation has been widely used to treat AD, but the mechanism of AD treatment remains unclear. OBJECTIVE： To observe changes in protein and factors in the hippocampus and frontal lobe of AD rats following NSCs transplantation, and to understand mechanism of action of NSCs transplantation in AD treatment. DESIGN, TIME AND SETTING： A randomized, controlled animal study was conducted at the First Clinical Hospital, Jilin University, China from July 2007 to March 2009. MATERIALS： NSCs were harvested from the hippocampus of 10 E16 Wistar rats. METHODS： A total of 57 male adult Wistar rats were equally and randomly divided into normal control, AD model and NSCs groups. AD models were established in the AD model and NSCs groups by bilateral removal of hippocampus. At 2 weeks postsurgery, NSCs were transplanted into the hippocampus of rats from the NSCs group. MAIN OUTCOME MEASURES： Protein levels were measured in the hippocampus of rats from normal control, NSCs and AD model groups using proteomics. Expression of choline acetyl transferase mRNA, glial fibrillary acidic protein and S100β was measured in the hippocampus and frontal lobe of rats using in situ hybridization and immunohistochemistry. RESULTS： Expression of choline acetyl transferase mRNA, heat shock protein 70, heat shock protein 90, F-actin and actin was significantly higher in the NSCs group compared with AD model group. Glial fibrillary acidic protein and S100β expression was less in the NSCs group compared with AD model group. CONCLUSlOIN： NSCs implanted into the brain may generate new neural cells, which can relieve damage to the cholinergic system and resist apoptosis. NSCs transplantation plays a protective role in the cholinergic system in the AD rats to some extent.展开更多
文摘Objective：To observe the therapeutic effect of Yangxue Qingnao Granule（养血清脑颗粒, YXQNG） on cognitive impairment induced by chronic cerebral hypoperfusion and to investigate its impact on oxidative stress,apoptosis,and the cholinergic system.Methods：Adult male Wistar rats were subjected to chronic cerebral hypoperfusion by permanent occlusion of bilateral common carotid arteries（2-VO）.Thirty rats were randomly assigned to one of the five treatment groups in a 1：1：1：1：1 ratio：sham operation plus normal saline treatment,2-VO plus normal saline treatment,2-VO plus YXQNG at a dose of 2 g·kg（-1）·d^（-1） or 4 g·kg（-1）·d^（-1）, or 2-VO plus rivastigmine 2 mgkg^（-1）·d^（-1）.The Morris water maze test was used to assess the spatial memory retrieval.Apoptosis,total antioxide capacity（T-AOC）,acetylcholine esterase（AchE） and choline acetyl transferase（ChAT） activities in the hippocampus and the cortex were investigated.Results：In the chronic cerebral hypoperfusion model,the 2-VO plus saline treatment resulted in impaired special learning as shown by the significantly prolonged escape latency and shorter swim time in the first quadrant as compared to the sham operation.The impairment was associated with apoptosis and significant decreases in T-AOC,AchE and ChAT activities in the hippocampus and the cortex.Treatment with YXQNG at either 2 g·kg（-1）·d^（-1） or 4 g·kg（-1）·d^（-1） dose,or rivastigmine resulted in significantly shorter escape latencies and longer swim time in the first quadrant.YXQNG at both doses,but not rivastigmine,had significant reduction in apoptosis,and significant increases in T-AOC and ChAT activity in both the hippocampus and the cortex.Unlike rivastigmine,neither dose of YXQNG showed significant reduction in AchE activity.Conclusions：YXQNG ameliorated cognitive impairment induced by chronic cerebral hypoperfusion.The protective effect may be mediated through its regulation of apoptosis and activities of T-AOC and C
基金the Jilin Pro-vincial Technology Devel-opment Foundation, No. 200505204, 200705129the Postdoctorate Founda-tion from Northeast Normal University, No. 111258000
文摘BACKGROUND： To date, no drugs are able to halt the progression of Alzheimer＇s disease （AD）. Neural stem cells （NSCs） transplantation has been widely used to treat AD, but the mechanism of AD treatment remains unclear. OBJECTIVE： To observe changes in protein and factors in the hippocampus and frontal lobe of AD rats following NSCs transplantation, and to understand mechanism of action of NSCs transplantation in AD treatment. DESIGN, TIME AND SETTING： A randomized, controlled animal study was conducted at the First Clinical Hospital, Jilin University, China from July 2007 to March 2009. MATERIALS： NSCs were harvested from the hippocampus of 10 E16 Wistar rats. METHODS： A total of 57 male adult Wistar rats were equally and randomly divided into normal control, AD model and NSCs groups. AD models were established in the AD model and NSCs groups by bilateral removal of hippocampus. At 2 weeks postsurgery, NSCs were transplanted into the hippocampus of rats from the NSCs group. MAIN OUTCOME MEASURES： Protein levels were measured in the hippocampus of rats from normal control, NSCs and AD model groups using proteomics. Expression of choline acetyl transferase mRNA, glial fibrillary acidic protein and S100β was measured in the hippocampus and frontal lobe of rats using in situ hybridization and immunohistochemistry. RESULTS： Expression of choline acetyl transferase mRNA, heat shock protein 70, heat shock protein 90, F-actin and actin was significantly higher in the NSCs group compared with AD model group. Glial fibrillary acidic protein and S100β expression was less in the NSCs group compared with AD model group. CONCLUSlOIN： NSCs implanted into the brain may generate new neural cells, which can relieve damage to the cholinergic system and resist apoptosis. NSCs transplantation plays a protective role in the cholinergic system in the AD rats to some extent.
