论文部分内容阅读
小胶质细胞变性对认识衰老相关的神经退变和神经退行性疾病的发病机制非常重要。本研究通过铁蛋白免疫组织化学方法来分析非痴呆和阿茨海默病患者大脑中的小胶质细胞形态特征。作者的主要假设为,铁储存蛋白-铁蛋白的表达提高小胶质细胞对退化的敏感性,尤其是在老年大脑中,因为衰老的小胶质细胞越来越无力维持铁环境稳定,而游离铁可促进氧化损伤。在24例34-97岁的病例中,小胶质细胞对铁蛋白的免疫反应被发现组成一个较大的HLA-DR抗体标记的小胶质细胞池。在老年尤其是AD大脑中,铁蛋白阳性的大部分小胶质细胞呈现出异常的形态学变化,即营养不良。铁蛋白阳性的营养不良小胶质细胞和AD组织中的老年斑之间并未发现空间相关性。对平均死亡时间(10.94±5.69)h的人脑组织的研究显示,小胶质细胞营养不良的出现不依赖于死亡时间,因而不是组织自溶的产物。这些结果均提示,包含铁储存和新陈代谢的小胶质细胞的变性可能是通过其高暴露于氧化应激。作者推论,铁蛋白免疫组织化学法可能是检测人脑小胶质细胞退行性变的有效方法。
Microglia degeneration is important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. This study analyzed the microglial morphology in the brain of non-demented and Alzheimer’s patients by ferritin immunohistochemistry. The authors’ main hypothesis is that the expression of ferritin, an iron storage protein, enhances the sensitivity of microglia to degeneration, especially in the aged brain, since the aged microglia become increasingly inoperable to maintain the stability of the ferrous environment free Iron can promote oxidative damage. In 24 cases of 34-97 years of age, microglial immune response to ferritin was found to form a larger pool of HLA-DR antibody-labeled microglia. Most ferritin-positive microglial cells exhibit abnormal morphological changes, ie malnutrition, in the elderly, especially AD brains. No correlation was found between ferritin-positive dystrophic microglia and age-related plaques in AD tissue. Studies of human brain tissue with an average death time (10.94 ± 5.69) h showed that the appearance of microglial malnutrition does not depend on the time of death and therefore is not a product of autolysis. These results suggest that degeneration of microglia containing iron storage and metabolism may be due to their high exposure to oxidative stress. The authors infer that ferritin immunohistochemistry may be an effective method to detect degeneration of human microglia.