基质细胞衍生因子-1α对大脑皮质局灶性梗死成年大鼠血管发生的影响  

Effect of stromal cell-derived factor-1α on angiogenesis in focal infarct in the cerebral cortex in adult rats

作　　者：凌莉[1] 张素平[1] 吉章阁[1] 黄惠鸿[1] 王慕真[1] 何锐[1] 邓婉青[1] 

机构地区：[1]广州市红十字会医院,暨南大学医学院第四附属医院神经内科,510220

出　　处：《国际脑血管病杂志》2014年第7期535-540,共6页International Journal of Cerebrovascular Diseases

基　　金：国家自然科学基金（81188098）;广东省自然科学基金（9451022002003396）

摘　　要：目的探讨外源性基质细胞衍生因子-1α（stromalcell-derivedfactor-1α，SDF-1α）对大脑皮质局灶性梗死成年大鼠梗死灶周围血管发生的影响及其可能机制。方法24只雄性成年Sprague—Dawley大鼠随机分为假手术组、SDF-1α治疗组、溶剂对照组和SDF-1α＋CXCR4拮抗剂组，每组6只。采用右侧大脑中动脉皮质支永久闭塞＋双侧颈总动脉暂时夹闭法制作大脑皮质局灶性梗死模型。SDF-1仪治疗组和溶剂对照组分别自右侧大脑中动脉皮质支闭塞后1h起经侧脑室注射SDF-1α（1μg／d）或等体积生理盐水，连续6d；SDF-1α＋CXCR4拮抗剂组自SDF-1α注射前皮下注射CXCR4拮抗剂AMm100（1mg／d），连续6d。所有大鼠处死前经腹腔注射5-溴脱氧尿嘧啶核苷（5-bromo--2deoxyuridine，BrdU）标记新增殖细胞。在模型制作后7d时行神经功能评分后处死各组大鼠，利用免疫荧光染色法检测梗死灶周围或假手术灶周围的血管密度、新生血管内皮细胞数目及CXCR4’细胞表达情况。结果在造模后7d时，SDF-1α治疗组神经功能评分较溶剂对照组和SDF-1α＋CXCR4拮抗剂组显著改善（P均〈0．01）。假手术组、溶剂对照组、SDF-1α组和SDF-1α＋CXCR4拮抗剂组大鼠梗死灶周围血管密度分别为2．1±0．3％、7．0±0．3％、10．0±0．9％和7．1±0．3％（F=232．469，P〈0．001），假手术组显著性低于SDF-1α组（P〈0．001），SDF-1α组显著性高于溶剂对照组（P=0．002）和SDF-1α＋CXCR4拮抗剂组（P=0．001）。假手术组、溶剂对照组、SDF-1α组和SDF-1α＋CXCR4拮抗剂组大鼠梗死灶周围BrdU’／层黏蛋白’细胞数量分别为21．7±3．1、79．7±6．0、176．0±12．5和90．3±6．9（F=391．550，P〈0．001），假手术组显著性少于SDF-1α组（P〈0．001），SDF-1α组显著性多于溶剂对照组和SDF-1α＋CXCR4拮抗剂组（P均〈0．001）。溶剂对照组、SDF-1α组和SDF-1α＋CXCR4拮抗剂组大Objective To investigate the effect of exogenous stromal cell-derived factor-1α （SDF-1α） on angiogenesis peri-infarct region in cerebral cortex in adult rats and its possNle mechanisms. Methods Twenty-four adult male Sprague-Dawley rats were randomly divided into four groups： sham operation,solvent control, SDF-1α treatment, and SDF-1α ± CXCR4 antagonist （n = 6 in each group）. A model of focal infarct in the cerebral cortex was induced by permanent ligation of the cortical branch of the right middle cerebral artery with temporary clip occlusion of both common carotid arteries. At 1 h after cortical branch occlusion of the right middle cerebral artery, SDF-1α （1μg/d） or equal volume of normal saline were injected via the lateral ventricle in the SDF-1α treatment group and solvent control group, and continued for 6 days. CXCR4 antagonist AMD3100 （1 mg/d） was injected subcutaneously before injecting SDF-lct in the SDF-1α± CXCR4 antagonists group, and continued for 6 days. Before all the rats were sacrificed, 5-bromo-2-deoxyuridine （BrdU） was injected intraperitoneally and their newly proliferated cells were labeled. At day 7 after modeling, the rats were sacrificed after neurological scores. Immunofluorescence staining was used to detect the vascular density, the numbers of neovasculature endothelial cells and the CXCR4 cells in the peri-infarct regions or sham operation regions. Results At 7 d after modeling, the neurological function of the SDF-1α treatment group was improved significantly compared with those of the solvent control group and the SDF-1α ＋ CXCR4 antagonist group （all P 〈 0. 01）. The vascular densities in the peri-infarct or sham operation regions in the groups of sham operation, solvent control, SDF-1α treatment, and SDF-1α ＋ CXCR4 antagonist were 2. 1 ±0. 3%, 7. 0 -±0. 3%, 10. 0± 0. 9% and 7. 1 ± 0. 3%, respectively （F = 232. 469, P 〈 0. 001）, and that in the sham operation was significantly lower than that in the SDF-1α group （P 〈0. 001�

关 键 词：脑梗死 脑缺血 新生血管化 生理性 趋化细胞因子CXCL12 干细胞 受体 CXCR4 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]