增龄脑中毛细血管形态及与神经元密度相关改变

Morphological and Quantatitive Capillary Changes in Aging Human Brain

目的 观察增龄脑中毛细血管形态变化及神经元和毛细血管密度的相对改变,探讨血管因素在脑老化中的作用。方法 以 28例正常增龄病例及 6例阿尔茨海默病 Alzheim er's disease AD 患者尸检脑标本为研究对象。应用荆豆凝集素 ulex europaeus agglutinin UEA 免疫组织化学及甲苯胺蓝等染色观察正常增龄病例额叶、枕叶、壳核、海马及 AD 患者海马的神经元、毛细血管形态改变,应用图像分析技术测算各部位神经元与毛细血管密度比值,并分析其与年龄之间的相关性。结果 老年及 AD 患者脑内毛细血管可见 诸多病理形态改变。正常增龄病例额叶、枕叶、壳核神经元和毛细血管数目及面积之比与年龄呈正相关。结论 脑老化中毛细血管可出现病理形态改变且数目相对减少,故血管因素可能是脑老化发生机制中的重要因素之一。

Objective To investigate morphological changes of capillary in aging brain and explore the role of vascular factor in brain aging. Methods Twenty-eight brains of individuals(mean age 65 years)who died without clinical or pathological involvement of nervous system and 6 brains of Alzheimer′s disease(AD)patients(mean age 83 years)were obtained at autopsy. Sections from frontal lobe, occipital lobe, striatum and hippocampus of normal subjects and sections from hippocampus of AD patients were used for hematoxylin eosin(HE),lox fast blue(LFB),toluidine blue stains and ulex europaeus agglutinin(UEA)immunostaining. After observations of morphological changes of neuron and capillary, computer-aid image analysis was performed to quantify numerical density and area density of neuron and capillary in frontal lobe, occipital lobe, putamen, CA3 sector of normal subjects and CA3 sector of AD patients. Numerical ratio and area ratio of neuron and capillary were then calculated. Correlations between neuron/capillary ratio and age were estimated using Pearson′s correlation test. Difference of neuron/capillary ratio in CA3 sectors between AD patients and advanced aged normal subjects(> 75 years)was analyzed with Student′s t-test. Results Several pathological microvascular changes, including increased tortuosity, looping, bundling, stringing, and effacement of endothelia were seen in aged subjects and more prevalent in AD patients. Numerical ratio and area ratio of neuron and capillary of frontal lobe, occipital lobe and putamen significantly increased with age in normal aging subjects. Conclusions Morphological changes and relative decrease in number and capacity of capillary in aging brain may reduce cerebral blood flow and metabolism, and consequently result in functional impairment of aging brain. Vascular factors may play an important role in the development of brain aging.