脑梗死患者海马β-淀粉样蛋白的表达

The expression of β-amyloid protein in hippocampus of patients with cerebral infarction

目的研究人脑梗死后β-淀粉样蛋白（Aβ）1-40和Aβ1-42在海马CA1区神经元中的表达。方法选取因脑梗死而死亡的尸检脑标本43例，并按缺血时间（发病至死亡时间）分为7组，选取因其他疾病死亡（非脑缺血）的尸检脑标本6例为对照组；应用苏木素咿红（HE）染色方法观察海马神经元形态变化；应用Aβ1-40和Aβ1-42免疫组织化学方法检测人脑梗死后海马CA1区两种蛋白在神经元中的表达情况；用末端脱氧核糖转移酶介导的dUTP缺口末端标记技术（TUNEL）标记凋亡神经元。结果海马CA1区，对照组Aβ1-40和Aβ1-42在神经元中均有微量表达，并且于缺血2h后表达均迅速增加，Aβ1-40在72h后达高峰[（36．30±2．67）个／高倍视野]，Aβ1-42在24～47h达高峰[（30．87±4．62）个／高倍视野]，以后有所回落，但仍高于对照组。缺血6～23h可检测到TUNEL阳性细胞，48～71h达高峰[（27．56±6．76）个／高倍视野]。2～5h受损神经元形态基本正常，24～47h神经元形态学变化较为明显，72h后，大部分神经元出现坏死特征。结论人脑梗死后海马CA1区Aβ1-40和Aβ1-42在神经元中的表达均增加，表明脑缺血可能导致这两种蛋白的聚集，同时Aβ的毒性作用可能对脑梗死后CA1区神经元的迟发性死亡起着一定的作用。

Objective To investigate the expression of β-amyloid protein （Aβ） 1-40 and Aβ1-42 in neurons of hippoeampal CA1 region after cerebral infarotion. Methods Totally 43 human brains with cerebral infarotion obtained at autopsy were investigated to clarify the possible accumulation of Aβ1-40 and Aβ1-42 in neurons of hippoeampus after cerebral infarotion. According to isehemie time, the specimens were divided into 7 groups. 6 brains from patients died of other diseases without cerebral isehemia were taken as controls. Morphological changes were analyzed by observing HE staining, and the time course of Aβ1-40 and Aβ1-42 immunoreaetivities in neurons of hippoeampal CA1 region after cerebral infarction were examined respectively. The terminal deoxyribonucleotide transferase （TdT）-mediated dUTP nick-end labeling （TUNEL） assessment was used to clarify the neuronal death in the hippoeampal CA1 region caused by cerebral infarotion. Results In neurons of the CA1 region, the immunoreaetivities of Aβ1-40 and Aβ1-42, both of which predominantly presented in the cytoplasm, were observed in both control and isehemie groups, and the accumulation of both Aβ1-40 and Aβ1-42 was increased dramatically in the isehemie groups. The staining of Aβ1-40 reached a peak after 72 hours （（36.30±2.67）/Hpf） and Aβ1-42 reached a maximum at 24-47 hours （（30.87±4.62）/Hpf）. The staining of TUNEL was predominantly localized in nucleus, and TUNEL positive cells were detectable at 6-23 hours, and markedly increased at 48-71 hours （（27.56±6.76）/hpf）. At 2-5 hours, most neurons had relative normal morphology; at 24-47 hours, the neurons showed a significant pathological morphology; after 72 hours, some neurons showed necrotic features. Conclusions The increase of Aβ1-40 and Aβ1-42 immunoreaetivities in neurons of hippoeampal CA1 region after cerebral infarotion indicate that the cerebral isehemia might promote conditions that are favorable to the accumulation of Aβ1-40 and Aβ1-42. The accumulation of the eytotoxie Aβ1-40 and Aβ1-42 fragments in the CA1 neurons, might in turn reflect its participation in the development of delaying neuronal death after the ischemic insult.