脑老化过程中组织形态学改变及S100蛋白表达

发布时间：2019-03-20 20:28

【摘要】： 近年来,随着中国进入老龄化社会步伐的加快,阿尔茨默病、帕金森病等“老年病”发病率逐步提高,患病人数逐年递增,已经成为一个严重的社会和医疗卫生问题。多年来研究表明,脑组织的增龄性变化在神经系统的疾病过程中发挥重要的作用,并具有某些共同的病理及病理生理改变,因此,对于脑组织的增龄性变化的病理改变的研究可以作为多种神经系统疾病的研究基础,并不断为之的防治提供新的思路。星型胶质细胞对维持血脑屏障完整性至关重要,且对突触传递、神经元新生均有影响;而活化的小胶质细胞在痴呆患者脑中增多;突触密度随年龄的增长而下降被认为是脑老化中普遍现象,因此研究小胶质细胞及星形胶质细胞以及突触密度随年龄的增长,在形态、数量上的改变对于研究人脑的老化过程以及病理生理改变具有重要的意义。 S100蛋白主要由胶质细胞特别是星形胶质细胞合成和分泌,在正常生理条件下浓度较低,起着稳定中枢神经系统的作用。在大脑衰老过程中S100含量亦明显升高,被认为是对增龄相关的脑结构和功能改变的有益反应。因此,研究S100蛋白在人脑中的增龄性改变以及这些改变同大脑其他的一些组织形态学的改变之间的关系,对于脑老化的研究具有一定的积极意义。目前,由于多种因素的限制,对于增龄脑的研究主要以动物模型为主,而以人类脑组织为基础的病理学研究相对较少,本课题以尸检增龄脑标本为研究对象,通过对增龄脑组织形态学的研究,观察脑老化过程中大脑额叶、枕叶、壳核、海马区的改变,并通过与S100蛋白表达的相关研究,从而进一步了解脑组织自然衰老的机制,以探索神经系统疾病的新的诊断治疗方法。研究内容:(1) GFAP阳性星形胶质细胞Ferritin阳性小胶质细胞在脑组织中的分布特点及其随龄变化. (2)光镜下可见SYNP免疫反应阳性物质呈大小不等的颗粒在脑组织中的分布特点及其随龄变化. (3)用免疫组织化学ABC法标记S100免疫阳性(S100IR)细胞,观察S100蛋白在成年脑和老年脑中的分布,探讨其表达的年龄相关变化及及其与胶质细胞随龄变化的关系。研究方法:以30例25-96岁无重要神经系统病史及神经病理改变的尸检脑标本为研究对象,结合免疫组化及图象分析技术,观察成年以后至老龄期间人脑额叶、枕叶、海马及基底节区的GFAP阳性星形胶质细胞Ferritin阳性小胶质细胞S100蛋白以及突触素的变化,并分析上述变化与年龄增长的相关性。结果:1.老年组GFAP阳性星型细胞的分布较成年人略广泛,有不同程度的增生、肥大。 2.老年组脑内铁蛋白阳性小胶质细胞的分布与成年组类似,但各部位灰质内小胶质细胞及活化的小胶质细胞数目较成年人不同程度地增多。 3.成年组和老年组脑中均可见棕褐色免疫反应的S100IR细胞,多为星形胶质细胞,但老年组额叶、枕叶、海马及基底核阳性细胞密度均显著增加,与星型胶质细胞、小胶质细胞的变化呈正相关。, 4. SYNP免疫反应阳性颗粒,弥散分布于皮层、壳核及海马灰质神经毡内,神经细胞、胶质细胞胞体内、突触密度与年龄呈现一定程度的负相关。结论:1.星型胶质细胞与小胶质细胞有随年龄增加而增加的趋势。正常老龄脑额叶、枕叶、壳核及海马区突触密度均出现不同程度下降,并与年龄呈现一定程度的负相关,未发现其与星型胶质细胞与小胶质细胞及S100蛋白显著相关。 2. S100IR细胞在脑中的分布具区域性差异,呈明显的年龄相关性增生,并与星型胶质细胞与小胶质细胞的随龄变化呈相关。 3. S100在人脑内与GFAP阳性的星型胶质细胞在研究的各部位都呈现了一定程度的正相关,与铁蛋白阳性的小胶质细胞在额叶、枕叶存在一定的相关性。
[Abstract]:In recent years, with the rapid development of the aging society in China, the incidence of Alzheimer's disease, Parkinson's disease and other "Geriatrics" has been gradually increased, and the number of sick people is increasing year by year, and has become a serious problem of social and health care. The study has shown that the age-increasing changes of brain tissue play an important role in the course of diseases of the nervous system, and have some common pathological and pathological changes, so, The study of the pathological changes of the age-related changes of the brain tissue can be used as a basis for the research of various nervous system diseases and provide new ideas for the prevention and treatment of the disease. Astrocytes are essential to the maintenance of the integrity of the blood-brain barrier and have an effect on synaptic transmission and neuronal neogenesis; the activated microglia increase in the brains of patients with dementia; and the decrease in the synaptic density with age is considered to be It is a common phenomenon in the aging of the brain, so the study of microglia and astrocyte and the growth of the synaptic density with age, in the form and number of changes in the aging process and pathophysiology of the study of the human brain S100 protein is mainly synthesized and secreted by glial cells, especially astrocytes, and in normal physiological conditions The lower concentration, which plays a role in stabilizing the central nervous system, is also considered to be a significant increase in S100 in the course of brain aging. The beneficial effects of age-related changes in brain structure and function are studied. Therefore, the changes in the age-related changes of S100 protein in the human brain and the correlation between these changes and the changes in the morphological changes of some other tissues of the brain are studied. It is of positive significance to study the aging of brain. At present, because of the limitation of many factors, the research on the age-increasing brain is mainly based on the animal model, and the pathological study based on human brain tissue is relatively small, this lesson The changes of the frontal lobe of the brain, the occipital lobe, the nucleus of the shell and the hippocampus of the brain during the aging of the brain were studied by the study of the morphology of the brain tissue of the age-increasing brain, and the correlation between the expression of S100 protein and the expression of S100 protein was studied. The mechanism of the natural aging of brain tissue to explore new methods of diagnosis and treatment of nervous system diseases. The distribution of the positive astrocyte Ferritin-positive microglia in the brain and its age-dependent changes. (2) The distribution of the positive substances of SYP immunoreaction in the brain was observed under light microscope and the change of age. (3) The immunocytochemical ABC method was used to mark S100 to be positive. (S100IR) The distribution of S100 protein in the brain of adult and the aged was observed, the age-related changes of the expression of S100 protein and their relationship with the age-related changes of the glial cells were discussed. Thirty-five-96-year-old necropsied brain specimens with no major neurological history and neurological changes were studied, and the frontal lobe of the human brain after adult to aging was observed by immunohistochemistry and image analysis. occipital lobe and the GFAP-positive astrocyte Ferritin-positive microglia S10 in the basal ganglia region The results were as follows:1. The distribution of GFAP positive star cells in the old group was more than that in the old group. In the elderly, the distribution of the positive microglia in the brain of the elderly group was similar to that of the adult group, but the number of microglia and the activated microglia in the gray matter of each part increased to a different extent than that of the adult. . 3. S100IR cells with brown-brown immune response were found in both the adult group and the old group, most of which were astrocytes, but the frontal lobe, occipital lobe, hippocampus and basal nucleus of the old group. positive cell density The degree of the microglia is obviously increased, and the change of the astrocyte and the microglia is positive. 4. The positive particles of the SYP were distributed in the cortex, the nucleus of the shell and the nerve-felt in the gray matter of the hippocampus, and the density of the synapse and the age of the neurons and the glial cells were in a certain degree. Conclusion:1. The astrocyte and microglia have a tendency to increase with age. The frontal lobe, occipital lobe and shell nucleus of the normal aging brain There was a negative correlation between the synaptic density in the hippocampus and the hippocampus, and there was a negative correlation with age, and no significant correlation was found between the astrocytes and the astrocytes and S100 proteins.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R361

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