Zhang Dingding, Wu Wei, Yan Huiying, Jiang Tianwei, Liu Ming, Yu Zhuang, Li Hua, Hang Chunhua
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People's Republic of China.
Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People's Republic of China.
Neurol Sci. 2016 Feb;37(2):219-26. doi: 10.1007/s10072-015-2391-y. Epub 2015 Oct 14.
A growing body of evidence suggests that inflammation plays a crucial role in cerebral aneurysm initiation, progression, and rupture. High-mobility group box 1 (HMGB1) is a non-histone nuclear protein that can serve as an alarmin to drive the pathogenesis of inflammatory disease. The purpose of this study was to investigate the expression of HMGB1 in the wall of ruptured and unruptured human cerebral aneurysms. Human cerebral aneurysms (25 ruptured and 16 unruptured) were immunohistochemically stained for HMGB1. As controls, four specimens of the middle cerebral arteries obtained at autopsy were also immunostained. Immunofluorescence double staining was used to determine HMGB1 cellular distribution. HMGB1 was nearly undetectable in the controls. All aneurysm tissues stained positive for HMGB1 monoclonal antibody, and expression of HMGB1 was more abundant in ruptured aneurysm tissue than unruptured aneurysms (p < 0.05). Furthermore, the expression of HMGB1 had no correlation with aneurysm size and time resected after the rupture. HMGB1 nuclear immunoreactivity was co-localized with immunoreactivity of CD3 in T lymphocytes, CD20 in B lymphocytes, CD68 in macrophages, α-SMA in smooth muscle cells, and CD31 in endothelial cells. Cytoplasmic HMGB1 localization was also detected in macrophages and T lymphocytes. Taken together, HMGB1 is expressed in the wall of human cerebral aneurysms and is more abundant in ruptured aneurysms than in unruptured ones. These data indicate a possible role of HMGB1 in the pathophysiology of human cerebral aneurysms.
越来越多的证据表明，炎症在脑动脉瘤的起始、进展和破裂过程中起着关键作用。高迁移率族蛋白B1（HMGB1）是一种非组蛋白核蛋白，可作为警报素驱动炎症性疾病的发病机制。本研究的目的是调查HMGB1在破裂和未破裂的人脑动脉瘤壁中的表达情况。对人脑动脉瘤（25个破裂的和16个未破裂的）进行HMGB1免疫组织化学染色。作为对照，对尸检时获取的4个大脑中动脉标本也进行了免疫染色。采用免疫荧光双重染色法确定HMGB1的细胞分布。在对照组中几乎检测不到HMGB1。所有动脉瘤组织对HMGB1单克隆抗体染色均呈阳性，且HMGB1在破裂动脉瘤组织中的表达比未破裂动脉瘤中更丰富（p<0.05）。此外，HMGB1的表达与动脉瘤大小及破裂后切除时间无关。HMGB1的核免疫反应性与T淋巴细胞中的CD3、B淋巴细胞中的CD20、巨噬细胞中的CD68、平滑肌细胞中的α-SMA以及内皮细胞中的CD31的免疫反应性共定位。在巨噬细胞和T淋巴细胞中也检测到了细胞质HMGB1定位。综上所述，HMGB1在人脑动脉瘤壁中表达，且在破裂动脉瘤中比未破裂动脉瘤中更丰富。这些数据表明HMGB1在人脑动脉瘤病理生理学中可能发挥作用。
