高同型半胱氨酸血症研究进展

高同型半胱氨酸血症可致偏头痛、痴呆、妊高症、抑郁症等多种疾病,被认为是心脑血管疾病的一个独立危险因素。本文就高同型半胱氨酸血症的发生及与部分疾病的关系进行综述。     

高同型半胱氨酸血症与脑血管病的研究进展

1969年，McCuuy首次报道1例少见的遗传型同型半胱氨酸血症的病例，意外地发现同型半胱氨酸（homocysteine，Hcy）与动脉粥样性疾病具有相关性。随着近年来Hcy和脑血管病关系的不断深入研究，Hcy在动脉粥样硬化发展中的重要性已经引起重视。目前认为Hcy是粥样硬化及冠心病、脑血管病的独立危险因素之一。现将近年来有关研究进展综述如下。     

高同型半胱氨酸血症对大鼠学习记忆能力和海马胆碱乙酰基转移酶表达的影响及叶酸的干预作用

目的 探讨高同型半胱氨酸血症(HHcy)对大鼠学习记忆能力和海马胆碱乙酰基转移酶(ChAT)表达的影响及叶酸的干预作用.方法 将30只Wistar大鼠随机分为正常对照组、HHcy组和叶酸干预组,每组10只.在大鼠饮水中添加蛋氨酸[1.0 g/(kg·d)]制作HHcy模型,叶酸干预组大鼠同时给予叶酸[0.4 mg/(kg·d)]灌胃,共持续8周.在实验前后测定各组血浆同型半胱氨酸(Hcy)、叶酸的浓度,给各组大鼠进行Morris水迷宫试验检查学习记忆能力,实验8周后用免疫组化染色观察大鼠海马区ChAT的表达水平.结果 与正常对照组和叶酸干预组比较,HHcy组水迷宫试验的逃避潜伏期明显延长,穿过平台次数明显减少,停留时间明显缩短(P＜0.05～0.01);HHcy组大鼠海马CA3区ChAT阳性细胞平均灰度值明显降低(P＜0.01).叶酸干预组与正常对照组以上各项检查结果 比较,差异无统计学意义.结论 HHcy导致大鼠学习记忆能力下降以及海马CA3区ChAT表达水平降低.补充叶酸能够起到很好的干预作用.     

高同型半胱氨酸血症与脑血管病的研究进展

1969年,McCully首次报道1例少见的遗传型同型半胱氨酸血症的病例,意外地发现同型半胱氨酸(homocysteine,Hcy)与动脉粥样性疾病具有相关性。随着近年来Hcy和脑血管病关系的不断深入研究,Hcy在动脉粥样硬化发展中的重要性已经引起重视。目前认为Hcy是粥样硬化及冠心病、脑血管病的独立危险因素之一。现将近年来有关研究进展综述如下。1Hcy的来源及代谢Hcy是一种含硫氨基酸,体内不能合成,只能从食物中的甲硫氨酸转变而来。甲硫氨酸首先生成S-腺苷甲硫氨酸(SAM),SAM去甲基生成S-腺苷同型半胱氨酸,再脱腺苷生成Hcy。Hcy在体内的代谢主要…     

脑卒中并发高同型半胱氨酸血症临床观察

近年来国内外研究认为高同型半胱氨酸血症可能是导致脑卒中新的独立危险因素。正常时Hcy水平为5～15mmol/L,当Hcy含量高于16mmol/L时,提示有高同型半胱氨酸血症[1]。为掌握急性脑卒中患者并发高同型半胱氨酸血症的临床特点,收集2007-12-2010-04在我科住院治疗     

高同型半胱氨酸血症对急性脑梗死短期预后的影响

目的探讨高同型半胱氨酸血症(HHcy)与急性脑梗死患者短期预后之间的关系。方法测定165例急性脑梗死患者空腹血浆Hcy浓度,将患者分为HHcy组和非HHcy组,并在其入院时和治疗14d后进行改良Rankin量表(MRS)评分。结果入院时非HHcy组和HHcy组患者MRS评分中生活自理(MRS评分≤2分)人数和不能自理(MRS评分≥3分)人数的百分比之间无统计学差异(P>0.05),经相同药物治疗14d后,非HHcy组患者中生活自理人数的百分比较HHcy组患者显著升高(P<0.01),不能自理人数的百分比较HHcy组患者显著降低(P<0.01),非HHcy组患者中生活不能自理得到改善人数的百分比较HHcy组患者也显著升高(P<0.01)。结论HHcy组急性脑梗死患者的短期预后比非HHcy组差,降低HHcy对于缺血性脑血管病具有重要的预防和治疗意义。     

脑梗死、TIA与高同型半胱氨酸血症的关系分析

目的观察高同型半胱氨酸血症与脑梗死度TIA之间的关系。方法应用高压液相色谱法（HPLC）对脑梗死、VIA和对照组中的健康体检者进行血浆同型半胱氨酸测定。结果脑梗死组病人的血浆同型半胱氨酸水平明显高于对照组（P〈0．01），而TIA组病人的血浆同型半胱氨酸水平高于对照组但无显著性差异（P〉0．05）。结论离同型半胱氨酸血症主要损伤中等及大血管而不是小血管。     

脑梗死与高同型半胱氨酸血症的相关性研究

目的探讨脑梗死与血浆同型半胱氨酸（HCY）水平的关系。方法120例脑梗死患者测定血浆HCY、叶酸、维生素B12、颈动脉内膜中层厚度、欧洲脑卒中量表评分等指标，并与60例健康对照者相比较。结果①脑梗死组的血浆HCY水平、颈动脉内膜中层厚度和甘油三酯明显高于对照组，而叶酸及维生素B12水平则低于对照组（P均〈0.01）。②脑梗死与HCY水平之间存在危险性的水平梯度，当HCY〉15μmol／L时，患者发生脑梗死的危险为正常人的5.909倍，而HCY≥20μmol／L时，惠者发生脑梗死的危险为正常人的10．545倍。③从各项监测指标的相对危险度来看，与脑梗死有关的因素分别为HCY、叶酸、维生素B12、甘油三酯、颈动脉内膜中层厚度和收缩压、舒张压。条件Logistic回归模型检验发现HCY、甘油三酯、高密度脂蛋白、颈动脉内膜中层厚度和收缩压为脑梗死的独立致病因素。④脑梗死组和对照组血浆HCY水平与血叶酸、维生素B12水平、欧洲脑卒中量表评分均呈显著负相关性；HCY水平与颈动脉内膜中层厚度呈显著正相关性。结论高同型半胱氨酸血症是脑梗死的独立致病因素，导致高同型半胱氨酸血症的原因可能是血浆内叶酸和维生素B12的降低。     

高同型半胱氨酸血症对急性脑梗死近期预后的影响

目的:探讨高同型半胱氨酸血症(Hhcy)对急性脑梗死近期预后的影响,以期为脑梗死干预治疗奠定理论基础。方法:测定121例急性脑梗死患者和52例健康对照者空腹血浆总同型半胱氨酸,以此结果将患者分为Hhcy组和非Hhcy组,对两组患者神经功能缺损和日常生活能力进行追踪观察。结果:Hhcy和非Hhcy组患者发病3天内神经功能缺损和发病第7、14天神经功能缺损和日常生活能力评分无显著差异(P>0.05);发病第30、90、180天,Hhcy组神经功能缺损评分显著高于非Hhcy组,而日常生活能力评分显著低于非Hhcy组(P<0.05)。结论:Hhcy不利于急性脑梗死患者近期康复。     

高同型半胱氨酸血症在癫痫患者中的研究进展

癫痫是多种原因导致的脑神经元高度同步异常放电的临床综合征,其发病率约为10～50/10万,患病率约为5‰～7‰,死亡率约为1～1.3/10万.多数癫痫患者需要长期甚至终生的抗癫痫治疗.近年来有大量文献资料和实验数据表明长期抗癫痫药物治疗可引起一些代谢性机能障碍,如肝肾功能损害,血小板功能损伤及血浆同型半胱氨酸(homocysteine,Hcy)、胆固醇、脂蛋白及尿酸水平升高.这些代谢机能障碍与临床上癫痫患者癫痫发作本身、抗癫痫药物(Antiepileptic drugs,AEDs)治疗[1]、癫痫患者合并脑萎缩[2]、动脉粥样硬化血栓形成[1]、骨密度丢失[3]、偏头痛、痴呆、妊高症、抑郁状态[4]等疾病密切相关.     

Applications of the Morris water maze in the study of learning and memory

The Morris water maze (MWM) was described 20 years ago as a device to investigate spatial learning and memory in laboratory rats. In the meanwhile, it has become one of the most frequently used laboratory tools in behavioral neuroscience. Many methodological variations of the MWM task have been and are being used by research groups in many different applications. However, researchers have become increasingly aware that MWM performance is influenced by factors such as apparatus or training procedure as well as by the characteristics of the experimental animals (sex, species/strain, age, nutritional state, exposure to stress or infection). Lesions in distinct brain regions like hippocampus, striatum, basal forebrain, cerebellum and cerebral cortex were shown to impair MWM performance, but disconnecting rather than destroying brain regions relevant for spatial learning may impair MWM performance as well. Spatial learning in general and MWM performance in particular appear to depend upon the coordinated action of different brain regions and neurotransmitter systems constituting a functionally integrated neural network. Finally, the MWM task has often been used in the validation of rodent models for neurocognitive disorders and the evaluation of possible neurocognitive treatments. Through its many applications, MWM testing gained a position at the very core of contemporary neuroscience research.     

Differential effects of kindling and kindled seizures on place learning in the morris water maze

There is some controversy about the role of long-term potentiation (LTP) in spatial learning. The authors have found that triggering generalized kindled seizures with stimulation of the perforant path disrupts spatial learning in the Morris water maze but that kindling per se does not affect spatial learning. It is suggested that abnormal electrical activity induced by high-frequency stimulation of the perforant path may have been responsible for the disruption of spatial learning previously attributed to LTP saturation.     

Music intervention improves spatial learning and memory and alters serum proteomics profiling in rats

Music has a long history of healing or mitigating physical and mental illness in the clinical setting. We aimed to test changes in behavioral cognition and serum proteomics in rats undergoing music intervention (MI). The Morris water maze (MWM) was used to evaluate spatial learning and memory in rats. Serum protein expression profiling was examined using magnetic bead‐based matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF‐MS). MI improved spatial learning and memory in both male and female rats. Peak 1708.61 (m/z values) was significantly increased in MI females vs. female controls. Peak 3925.09 (m/z values) was significantly reduced in MI males versus male controls. The two differential serum peptide peaks (m/z values: 1708.61, 3925.09) were further sequence identified as regions of proteins Desmin and Acsm1. Western blot and immunofluorescence testing of Desmin expression showed consistent results on proteomics analysis. MI plays an important role in behavioral cognition and protein expression in rats. This study provides a foundation in proteomics that suggests that MI might improve spatial learning and memory ability.     

Stress impairs performance in spatial water maze learning tasks

The water maze task has been developed to test spatial learning abilities in rats or mice, and is widely used. Though it has been reported before that numerous cognitive abilities are of importance for learning this task, poor performance is usually interpreted as an impairment of spatial memory formation. Previous investigations that tried to correlate long-term potentiation (LTP) of synaptic transmission with spatial learning abilities in rats reported that injection of drugs or specific gene deletions which blocked the expression of LTP correlated with learning impairments of spatial tasks in a water maze. Recent studies, however, have shown that pretraining enables these animals to learn such spatial tasks even though LTP was still found to be blocked. I investigated to what degree altered fear condition and stress perception could account for the impaired spatial learning when no pretraining is given. In a fear habituation task, unhandled rats preferred a dark over a well lit chamber more than handled animals did, but unhandled rats favoured the lit chamber more in an active avoidance task. They also performed poorly in a spatial water maze task compared with handled rats. Rats pretrained in a radial arm maze performed better in a water maze than non-pretrained rats. No difference between groups was found in a non-spatial water maze task. On the other hand, when pretrained in a water maze, rats performed only marginally better in a radial arm maze compared to non-pretrained animals. Since animals have to be handled to learn a radial arm maze, the difference in this task was not due to stress but most probably due to getting accustomed to the room dimensions prior to learning the spatial task. The results suggest that impaired learning of spatial tasks in the water maze can be due to increased stress and decreased fear conditioning without actually affecting spatial learning abilities. These results question the interpretations of the results of some previously published results of spatial water maze tasks.     

Spatial learning and memory, maze running strategies and cholinergic mechanisms in two inbred strains of mice

The acquisition process of the radial maze task was studied in two inbred strains of mice, C57BL/6 and DBA/2. A quantitative and qualitative evaluation of performance was performed and the pretest level of activity was measured. The results showed a significant correlation between activity and performance since the highly active C57BL/6 mice exhibited better performance of the radial maze task than the less active DBA/2 mice. Moreover, for correct trials, strain-dependent maze-running strategies were observed: while both strains displayed about the same percentage of clockwise and spatial strategies, it was observed that among the spatial strategies C57BL/6 used a larger number of different correct solutions. Subsequently, the effect of scopolamine administration on working memory processes was assessed in sequential and discrete trials. A different reactivity of each strain to anti-cholinergic treatment was found in discrete trials since only DBA/2 mice were impaired. The effect of scopolamine is discussed in relation to the different models of information processing involved in learning and memorizing the experimental rule.     

Non-spatial water radial-arm maze learning in mice

Recently, we published a method for examining working and reference memory in mice using a spatial version of the water radial-arm maze. Here we describe a non-spatial version of the same maze. BXSB mice were able to learn the maze as shown by the decrease in the number of working and reference memory errors over sessions. This maze was used to examine learning differences between males and females and between mice with misplaced clusters of neurons in layer I of cortex (ectopias) and those without. In a prior study using the spatial version of the water radial-arm maze, male BXSB mice had poorer working memory than females during the acquisition phase. Similarly, in this study male BXSB mice demonstrated impaired working memory during the asymptotic phase of non-spatial radial-arm maze learning. Two prior studies showed that mice with neocortical ectopias demonstrated working memory impairments compared to non-ectopic littermates in the spatial version of the water radial-arm maze. Contrary to this, in the non-spatial radial-arm maze used here, ectopic mice were not impaired in working memory and showed better memory when the working memory 'load' was the highest. Overall, both versions of the maze can be useful tools to assess spatial and non-spatial working and reference memory in mice.     

影响小鼠Morris水迷宫成绩的因素探讨及改进措施

Morris水迷宫自英国心理学家Richard Morris于1981年首次使用以来,已成为一种研究与海马功能直接相关的空间学习记忆机制的标准模式,能较准确地反映动物的空间参考记忆能力[1].Morris水迷宫能为考察实验动物空间认知能力提供较多的评价指标,全面记录其认知加工过程,客观地反映其认知水平.但是,Morris水迷宫的实施过程中还有很多影响其准确性和可靠性的因素存在,如实验动物的选择、实验设计、实验的实施过程等.因此,笔者现就影响小鼠Morris水迷宫成绩的若干因素(Morris水迷宫自身因素及小鼠主观因素等)进行综述,以期为实验工作者们减少误差提供一些帮助.     

Effects of spaced learning in the water maze on development of dentate granule cells generated in adult mice

New dentate granule cells (GCs) are generated in the hippocampus throughout life. These adult‐born neurons are required for spatial learning in the Morris water maze (MWM). In rats, spatial learning shapes the network by regulating their number and dendritic development. Here, we explored whether such modulatory effects exist in mice. New GCs were tagged using thymidine analogs or a GFP‐expressing retrovirus. Animals were exposed to a reference memory protocol for 10–14 days (spaced training) at different times after newborn cells labeling. Cell proliferation, cell survival, cell death, neuronal phenotype, and dendritic and spine development were examined using immunohistochemistry. Surprisingly, spatial learning did not modify any of the parameters under scrutiny including cell number and dendritic morphology. These results suggest that although new GCs are required in mice for spatial learning in the MWM, they are, at least for the developmental intervals analyzed here, refractory to behavioral stimuli generated in the course of learning in the MWM. © 2015 Wiley Periodicals, Inc.     

Wendan decoction improves learning and memory deficits in a rat model of schizophrenia

An experimental model of schizophrenia was established using dizocilpine (MK-801). Rats were intragastrically administered with Wendan decoction or clozapine for 21 days prior to establishing the model. The results revealed that the latency of schizophrenia model rats to escape from the hidden platform in the Morris water maze was significantly shortened after administration of Wendan decoction or clozapine. In addition, the treated rats crossed the platform significantly more times than the untreated model rats. Moreover, the rate of successful long-term potentiation induction in the Wendan decoction group and clozapine group were also obviously increased compared with the model group, and the population spike peak latency was significantly shortened. These experimental findings suggest that Wendan decoction can improve the learning and memory ability of schizophrenic rats to the same extent as clozapine treatment.     

Chronic caloric restriction reduces tissue damage and improves spatial memory in a rat model of traumatic brain injury

Although it has been known for some time that chronic caloric or dietary restriction reduces the risk of neurodegenerative disorders and injury following ischemia, the possible role of chronic restriction in improving outcomes after traumatic brain injury (TBI) has not been previously studied. Therefore, 2‐month‐old male Sprague‐Dawley rats were divided into two dietary groups, an ad libitum fed group (AL) and a caloric‐restriction group (CR) that was provided with 70% of the food intake of AL rats (n = 10/group). After 4 months, a weight‐drop device (300 g) was used to produce a 2‐mm bilateral medial frontal cortex contusion following craniotomy. Additional animals in each dietary group (n = 10) were used as sham‐operated controls. The CR diet resulted in body weights that were reduced by 30% compared with AL controls. Not only did CR decrease the size of the cortical lesion after injury, there were marked improvements in spatial memory as measured by Morris water maze that included an increase in the number of animals successfully finding the platform as well as significantly reduced time to finding the hidden platform. Western analysis, used to examine the expression of proteins that play a role in neuronal survival, revealed significant increases in brain‐derived neurotrophic factor (BDNF) in the cortical region around the site of injury and in the hippocampus in CR rats after injury. These findings suggest that molecular mechanisms involved in cell survival may play a role in reducing tissue damage and improving cognition after TBI and that these mechanisms can be regulated by dietary interventions. © 2010 Wiley‐Liss, Inc.