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磺酰脲受体 1 在人脑梗死中的表达。

Sulfonylurea receptor 1 expression in human cerebral infarcts.

机构信息

Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201-1595, USA.

出版信息

J Neuropathol Exp Neurol. 2013 Sep;72(9):871-83. doi: 10.1097/NEN.0b013e3182a32e40.

Abstract

In animal models of stroke, sulfonylurea receptor 1 (Sur1), a member of the adenosine triphosphate binding cassette transporter gene family, is transcriptionally upregulated in neural and vascular cells in which it plays a leading role in edema formation and necrotic cell death. To date, expression of Sur1 in the brains of humans with cerebral infarcts has not been systematically evaluated. We examined Sur1 expression in postmortem specimens obtained from 13 patients within the first 31 days after focal infarcts, 5 patients with lacunar infarcts, and 6 normal control brains using immunohistochemistry. Elevated immunoreactivity for Sur1 was detected in all cases of focal infarcts, with 3 distinct temporal patterns of expression: 1) neurons and endothelium showed the greatest elevation during the first week, after which levels declined; 2) astrocytes and microglia/macrophages showed progressive increases during the first 31 days; and 3) neutrophils near the infarct showed prominent immunoreactivity that did not change over time. Upregulation of Sur1 was corroborated using in situ hybridization for Abcc8 mRNA. Sulfonylurea receptor 1 immunoreactivity in lacunar infarcts was less prominent and more sporadic than in nonlacunar infarcts. In conjunction with previous studies, these data suggest that Sur1 may be a promising treatment target in patients with acute cerebral infarction.

摘要

在中风的动物模型中,磺酰脲受体 1(Sur1)是三磷酸腺苷结合盒转运体基因家族的成员,在神经和血管细胞中转录上调,在水肿形成和坏死性细胞死亡中发挥主导作用。迄今为止,尚未系统评估过患有脑梗死的人类大脑中 Sur1 的表达。我们使用免疫组织化学方法检查了 13 例局灶性梗死后 31 天内、5 例腔隙性梗死患者和 6 例正常对照大脑中的 Sur1 表达。在所有局灶性梗死病例中均检测到 Sur1 免疫反应性升高,表达具有 3 种不同的时间模式:1)神经元和内皮细胞在第一周内升高最明显,之后水平下降;2)星形胶质细胞和小胶质细胞/巨噬细胞在 31 天内逐渐增加;3)梗死附近的中性粒细胞表现出明显的免疫反应性,且随时间不变。Abcc8mRNA 的原位杂交证实了 Sur1 的上调。腔隙性梗死中的 Sur1 免疫反应性不如非腔隙性梗死明显且更为分散。结合先前的研究,这些数据表明 Sur1 可能是急性脑梗死患者有希望的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea06/3771575/1082303442dc/nen-72-871-g002.jpg

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