艾司西酞普兰对慢性脑缺血大鼠认知功能的影响
发布时间：2018-07-24 12:02
【摘要】：背景与目的 随着科技的发展，人民生活水平的提高，人们寿命的延长，生活节奏的加快以及环境污染的加重，脑卒中发病率和致残率程逐年增高的趋势。脑卒中不仅可以引起偏瘫、偏身感觉异常、偏盲、失语、实用等一系列神经系统缺失样症状体征，还可以引起认知功能障碍以及与心理、生理、社会因素综合作用引起患者情绪低落、自罪自责、兴趣减少为主要表现的卒中后抑郁（post strokedepression，PSD)。PSD是多种因素综合作用的结果，无论国内还是国外，其发病率普遍较高，国外报道多集中在30%-50%之间，国内报道的差异性较大，分布在34.2%-79%之间。PSD不仅影响脑卒中患者神经功能的恢复，还给患者给家属带来额外的经济及精神负担，因此PSD的正规治疗不可忽视。5-HT再摄取抑制剂（selective serotonin reuptake inhibitors,SSRIs）可以改善PSD患者的抑郁状态、加快神经功能恢，加之其较少的消化道、头疼及QT间期延长等不良反应，在临床中最常用于老年PSD患者，，然而该药对脑卒中患者认知功能的影响众说纷纭，因此探讨SSRIs对慢性脑缺血患者认知功能的影响及其作用机制显得极为迫切和重要。 慢性脑缺血是中枢神经系统一种常见的病理状态。慢性脑缺血或脑灌注不足常伴发于血管性痴呆（Vascular dementia，VD)、脑动脉硬化、Binswanger病、Alzheimer病以及动静脉畸形等多种脑血管疾病的病理过程中,发病早期以认知功能损害为主要表现,最终可能导致持久或进展性认知与神经功能障碍。大量研究表明5-羟色胺再摄取抑制剂（SSRIs）对兴奋性氨基酸，氧化应激及缺血缺氧等多种机制造成的脑损伤有保护作用。Steckler T等学者认为2-VO大鼠学习能力的下降与额叶皮质和海马5-羟色胺的迟发性下降有关。因此我们推测，5-羟色胺再摄取抑制剂可能改善慢性脑缺血患者的认知功能。艾司西酞普兰是一种强效的5-羟色胺再摄取抑制剂类抗抑郁药(SSRI)，与其同类药物相比，对5-HT受体选择性更高，起效迅速，被广泛用于老年抑郁和卒中后抑郁的预防与治疗。Choong Hyun Lee等人证实了30mg/kg艾司西酞普兰后处理缺血再灌注的大鼠，可以促进海马CA1区BDNF的表达，并且保护海马CA1区由缺血诱导的神经元死亡，而对于慢性脑缺血所致的认知障碍影响研究国内外尚未见报道。本实验采用2VO模型大鼠，应用水迷宫、Western blot以及高尔基染色观察艾司西酞普兰对慢性脑缺血大鼠认知功能及海马区BDNF含量的影响。 材料与方法 SD大鼠（健康雄性）240只，约24周龄，体重约450g，由郑州大学医学院实验动物供应中心提供，随机分为假手术组、模型组和实验组，选给药后1、2、4、8周四个时间点，每组20只。实验组为2VO模型大鼠每天给予30mg/kg·dESC灌胃，采用双侧颈总动脉永久性阻断法（2VO）建立慢性脑缺血模型，选给药满1、2、4、8周四个时间点，通过Morris水迷宫检测各组大鼠的认知功能，Western blot检测大鼠海马区BDNF的表达，高尔基染色观察神经元树突长度、分支及树突棘密度的变化。 结果 1．ESC对慢性脑缺血大鼠认知功能的影响 假手术组大鼠个时间点比较逃避潜伏期无统计学差别（P0.05）：同一观察点，与对照组相比实验组大鼠逃避潜伏期显著缩短（P0.05），实验组与模型组的逃避潜伏期均较假手术组显著延长（P0.05）。 2．ESC对慢性脑缺血大鼠海马区BDNF表达水平的影响 同一观察点，实验组和模型组海马区BDNF含量较假手术组减少(P0.05),实验组海马区BDNF含量较模型组增多（P0.05)。 3．ESC对慢性脑缺血大鼠海马区大锥体细胞形态的影响 模型组和实验组大鼠海马CA1区大锥体细胞树突长度、分支及树突棘密度较假手术组明显减少(P0.05)，实验组海马CA1区大锥体细胞树突分支及长度、树突棘密度较模型组明显增多（P0.05）。 结论 艾司西酞普兰能明显延缓慢性脑缺血大鼠认知功能障碍的进展,其机制可能是通过促进BDNF表达从而改善学习记忆能力。
[Abstract]:Background and purpose
With the development of science and technology, the improvement of people's living standard, the prolongation of life life, the quickening of the rhythm of life and the aggravation of environmental pollution, the incidence of stroke and the rate of disability are increasing year by year. Stroke can not only cause hemiplegia, abnormal feeling of deviation, hemiinas, loss of speech, and practicality, but also a series of symptoms and signs of lack of nerve system. Post strokedepression (PSD).PSD, which can cause cognitive dysfunction and psychological, physiological and social factors to cause depression, self reproach and decrease of interest (PSD), is the result of a combination of various factors. Between 30%-50%, the difference in domestic reports is larger. The distribution of.PSD between 34.2%-79% not only affects the recovery of neural function of stroke patients, but also brings extra economic and spiritual burden to the family members, so the regular treatment of PSD can not ignore the.5-HT reuptake inhibitor (selective serotonin reuptake inhibitors, SSRIs) can be changed. The depressive state of patients with good PSD, quickening the nerve function restorer, combined with its less digestive tract, headache and prolongation of QT interval, is most commonly used in the elderly patients with PSD. However, the influence of the drug on cognitive function of stroke patients is different, so the effect of SSRIs on cognitive function of patients with chronic cerebral ischemia and its action machine are discussed. The system is very urgent and important.
Chronic cerebral ischemia is a common pathological state of the central nervous system. Chronic cerebral ischemia or insufficient cerebral perfusion is often associated with vascular dementia (Vascular dementia, VD), cerebral arteriosclerosis, Binswanger's disease, Alzheimer disease, and arteriovenous malformation, and the early onset of cognitive impairment is the main table. A large number of studies have shown that the 5- hydroxytryptamine reuptake inhibitor (SSRIs) has protective effects on brain damage caused by various mechanisms such as excitatory amino acids, oxidative stress and ischemic anoxia..Steckler T and other scholars believe that the learning ability of 2-VO rats decreases with the frontal cortex and the sea. Therefore, we speculate that the 5- serotonin reuptake inhibitor may improve the cognitive function of patients with chronic cerebral ischemia. Essicitalopram is a powerful 5- serotonin reuptake inhibitor type antidepressant (SSRI), which is more selective to 5-HT receptor, rapid and widely used than its similar drugs, as compared with its similar drugs. The prevention and treatment of depression and post-stroke depression in the elderly.Choong Hyun Lee et al. Confirmed that the rats after 30mg/kg isisalopram treatment with ischemia-reperfusion can promote the expression of BDNF in the CA1 region of the hippocampus, and protect the neuronal death induced by ischemia in the hippocampal CA1 region, and the effect of the cognitive impairment on chronic cerebral ischemia The 2VO model rats were used to observe the effects of Ai Sciplan on cognitive function and the content of BDNF in hippocampus of rats with chronic cerebral ischemia by using water maze, Western blot and Golgi staining.
Materials and methods
SD rats (healthy male) 240, about 24 weeks old, weight about 450g, were provided by the experimental animal supply center of Zhengzhou University medical college. They were randomly divided into sham operation group, model group and experimental group, and 20 rats in each group were given a time point on Thursday after the drug administration. The experimental group was given 30mg/kg / dESC gavage every day for the 2VO model rats, and the bilateral common carotid artery was permanent. The chronic cerebral ischemia model was established by blocking method (2VO). The drug was selected for the time point of 1,2,4,8 on Thursday. The cognitive function of rats in each group was detected by the Morris water maze. The expression of BDNF in the hippocampus of the rats was detected by Western blot. The length of the dendrites, the branches and the density of the dendritic spines were observed by Golgi staining.
Result
1. Effect of ESC on cognitive function in rats with chronic cerebral ischemia
There was no significant difference in the escape latency between the rats in the sham operation group (P0.05): the escape latency of the rats in the experimental group was significantly shorter than that in the control group (P0.05), and the escape latency of the experimental group and the model group was significantly longer than that of the sham group (P0.05).
2. Effect of ESC on BDNF Expression in Hippocampus of Rats with Chronic Cerebral Ischemia
At the same observation point, the levels of BDNF in hippocampus of experimental group and model group were lower than those of sham operation group (P 0.05), and the levels of BDNF in hippocampus of experimental group were higher than those of model group (P 0.05).
3. Effect of ESC on morphology of macropyramidal cells in hippocampus of rats with chronic cerebral ischemia
In the model group and the experimental group, the dendrite length, the branch and the density of the dendritic spines in the hippocampal CA1 region were significantly lower than those in the sham operation group (P0.05). The dendritic branches and length of the large pyramidal cells in the hippocampus CA1 region and the density of the dendritic spines increased significantly (P0.05).
conclusion
Ai Sciplan can significantly delay the progress of cognitive impairment in rats with chronic cerebral ischemia. The mechanism may be to improve the learning and memory ability by promoting the expression of BDNF.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743
本文编号：2141318
[Abstract]:Background and purpose
With the development of science and technology, the improvement of people's living standard, the prolongation of life life, the quickening of the rhythm of life and the aggravation of environmental pollution, the incidence of stroke and the rate of disability are increasing year by year. Stroke can not only cause hemiplegia, abnormal feeling of deviation, hemiinas, loss of speech, and practicality, but also a series of symptoms and signs of lack of nerve system. Post strokedepression (PSD).PSD, which can cause cognitive dysfunction and psychological, physiological and social factors to cause depression, self reproach and decrease of interest (PSD), is the result of a combination of various factors. Between 30%-50%, the difference in domestic reports is larger. The distribution of.PSD between 34.2%-79% not only affects the recovery of neural function of stroke patients, but also brings extra economic and spiritual burden to the family members, so the regular treatment of PSD can not ignore the.5-HT reuptake inhibitor (selective serotonin reuptake inhibitors, SSRIs) can be changed. The depressive state of patients with good PSD, quickening the nerve function restorer, combined with its less digestive tract, headache and prolongation of QT interval, is most commonly used in the elderly patients with PSD. However, the influence of the drug on cognitive function of stroke patients is different, so the effect of SSRIs on cognitive function of patients with chronic cerebral ischemia and its action machine are discussed. The system is very urgent and important.
Chronic cerebral ischemia is a common pathological state of the central nervous system. Chronic cerebral ischemia or insufficient cerebral perfusion is often associated with vascular dementia (Vascular dementia, VD), cerebral arteriosclerosis, Binswanger's disease, Alzheimer disease, and arteriovenous malformation, and the early onset of cognitive impairment is the main table. A large number of studies have shown that the 5- hydroxytryptamine reuptake inhibitor (SSRIs) has protective effects on brain damage caused by various mechanisms such as excitatory amino acids, oxidative stress and ischemic anoxia..Steckler T and other scholars believe that the learning ability of 2-VO rats decreases with the frontal cortex and the sea. Therefore, we speculate that the 5- serotonin reuptake inhibitor may improve the cognitive function of patients with chronic cerebral ischemia. Essicitalopram is a powerful 5- serotonin reuptake inhibitor type antidepressant (SSRI), which is more selective to 5-HT receptor, rapid and widely used than its similar drugs, as compared with its similar drugs. The prevention and treatment of depression and post-stroke depression in the elderly.Choong Hyun Lee et al. Confirmed that the rats after 30mg/kg isisalopram treatment with ischemia-reperfusion can promote the expression of BDNF in the CA1 region of the hippocampus, and protect the neuronal death induced by ischemia in the hippocampal CA1 region, and the effect of the cognitive impairment on chronic cerebral ischemia The 2VO model rats were used to observe the effects of Ai Sciplan on cognitive function and the content of BDNF in hippocampus of rats with chronic cerebral ischemia by using water maze, Western blot and Golgi staining.
Materials and methods
SD rats (healthy male) 240, about 24 weeks old, weight about 450g, were provided by the experimental animal supply center of Zhengzhou University medical college. They were randomly divided into sham operation group, model group and experimental group, and 20 rats in each group were given a time point on Thursday after the drug administration. The experimental group was given 30mg/kg / dESC gavage every day for the 2VO model rats, and the bilateral common carotid artery was permanent. The chronic cerebral ischemia model was established by blocking method (2VO). The drug was selected for the time point of 1,2,4,8 on Thursday. The cognitive function of rats in each group was detected by the Morris water maze. The expression of BDNF in the hippocampus of the rats was detected by Western blot. The length of the dendrites, the branches and the density of the dendritic spines were observed by Golgi staining.
Result
1. Effect of ESC on cognitive function in rats with chronic cerebral ischemia
There was no significant difference in the escape latency between the rats in the sham operation group (P0.05): the escape latency of the rats in the experimental group was significantly shorter than that in the control group (P0.05), and the escape latency of the experimental group and the model group was significantly longer than that of the sham group (P0.05).
2. Effect of ESC on BDNF Expression in Hippocampus of Rats with Chronic Cerebral Ischemia
At the same observation point, the levels of BDNF in hippocampus of experimental group and model group were lower than those of sham operation group (P 0.05), and the levels of BDNF in hippocampus of experimental group were higher than those of model group (P 0.05).
3. Effect of ESC on morphology of macropyramidal cells in hippocampus of rats with chronic cerebral ischemia
In the model group and the experimental group, the dendrite length, the branch and the density of the dendritic spines in the hippocampal CA1 region were significantly lower than those in the sham operation group (P0.05). The dendritic branches and length of the large pyramidal cells in the hippocampus CA1 region and the density of the dendritic spines increased significantly (P0.05).
conclusion
Ai Sciplan can significantly delay the progress of cognitive impairment in rats with chronic cerebral ischemia. The mechanism may be to improve the learning and memory ability by promoting the expression of BDNF.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743
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