人脑动静脉畸形出血相关的危险因素及其病灶的内皮祖细胞与SDF-1的关系

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目的探讨人脑动静脉畸形(arteriovenous malformation, AVM)患者出血相关因素,以及脑AVM病灶组织中内皮祖细胞(endothelial progenitor cells,EPCs)数量与不同年龄中基质细胞衍生因子1(stromal cell-derived factor-1,SDF-1)的关系。方法回顾性分析2012年5月−2018年10月期间进行手术治疗的130例脑AVM患者资料,对脑AVM出血相关因素进行单因素及多因素logistic分析。在130例患者中随机抽取40例在术中切除的脑AVM组织石蜡标本作为研究组,其中按是否出血分为颅脑出血组(24例)、颅脑未出血组(16例),并按照年龄分为50岁组(13例)。另选取同期8例癫痫手术患者大脑皮质石蜡标本作为对照组。采用免疫组化染色法检测两组脑组织标本中CD34和血管内皮生长因子受体2(KDR2)阳性表达以判断鉴定EPCs;采用免疫荧光双染法进行KDR2、CD34阳性定位以判断EPCs定位,并进行SDF-1表达检测。结果脑AVM病灶大小<3 cm、深部脑AVM及单一静脉引流是引起脑AVM出血的独立危险因素。免疫组化染色结果显示,研究组AVM病灶组织中KDR2、CD34阳性表达,而对照组脑组织无表达;免疫荧光双染显示,EPCs主要位于血管壁边缘,而SDF-1能与平滑肌细胞标志物α-平滑肌肌动蛋白(alpha-smooth muscle actin,α-SMA)和内皮细胞标志物CD31共染,脑AVM组织中SDF-1表达高于对照组。<20岁组AVM组织EPCs数量高于其他年龄组患者(P<0.05)。颅脑出血组与未出血组间EPCs数量差异无统计学意义。结论病灶<3 cm、单一静脉引流和发生于脑深部的AVM易出血,需引起关注。SDF-1可能参与了EPCs的调控,EPCs可能参与了AVM中的血管重建。“,”ObjectiveTo explore the related risk factors of hemorrhage in human brain cerebral arteriovenous malformations (AVM) and the relationship between endothelial progenitor cells (EPCs) content and stromal cell-derived factor-1 (SDF-1) in different ages.MethodsA retrospective analysis was conducted on 130 patients with cerebral AVM who underwent surgical treatment from May 2012 to October 2018. Univariate and multivariate logistic analysis was used to investigate the related risk factors of cerebral AVM hemorrhage. Forty paraffin specimens of human brain AVM were harvested from 24 cases of cerebral hemorrhage patients and 16 cases of non-cerebral hemorrhage patients Paraffin samples of cerebral cortex from 8 patients with epilepsy during the same period were selected as control. Positive expression of CD34 and vascular endothelial growth factor receptor 2 (KDR2) in brain tissue samples of both groups were used to identify EPCs. Immunofluorescence double staining was used for KDR2 and CD34 positive localization to determine EPCs localization, and SDF-1 expression detection was performed. ResultsThe size of brain AVM<3 cm, deep brain AVM and single venous drainage are independent risk factors for cerebral AVM hemorrhage. Immunohistochemical results showed that CD34 and KDR2 were expressed in cerebral AVM group, but not in the control group. Double immunofluorescence staining showed that EPCs mainly existed at the edge of vascular wall, while SDF-1 could co-stain with alpha-smooth muscle actin (α-SMA) positive cells and CD31 positive cells. SDF-1 expression in brain AVM tissue was higher than that in control group. There were significant differences in the number of EPCs among the patients of different ages (P0.05).Conclusion Brain AVM (<3 cm), single venous drainage and deep brain AVM are independent risk factors for cerebral AVM hemorrhage. In human brain AVM, EPC appears high level but decrease with age, which may play a role in vascular remodeling in AVM.
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