国际脑血管病杂志
國際腦血管病雜誌
국제뇌혈관병잡지
INTERNATIONAL JOURNAL OF CEREBROVASCULAR DISEASES
2014年
7期
535-540
,共6页
凌莉%张素平%吉章阁%黄惠鸿%王慕真%何锐%邓婉青
凌莉%張素平%吉章閣%黃惠鴻%王慕真%何銳%鄧婉青
릉리%장소평%길장각%황혜홍%왕모진%하예%산완청
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
腦梗死%腦缺血%新生血管化,生理性%趨化細胞因子CXCL12%榦細胞%受體,CXCR4%大鼠
뇌경사%뇌결혈%신생혈관화,생이성%추화세포인자CXCL12%간세포%수체,CXCR4%대서
Brain Infarction%Brain Ischemia%Neovascularization,Physiologic%Chemokine CXCL12%Stem Cells%Receptors,CXCR4%Rats
目的 探讨外源性基质细胞衍生因子-1α(stromal cell-derived factor-1α,SDF-1 α)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-1α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AMD3100(1 mg/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-2-deoxyuridine,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-1 α+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拮抗剂组大鼠梗死灶周围CXCR4+细胞数量分别为59.3±4.5、120.3 ±13.9和62.9±5.9(F=85.052,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).结论 SDF-1α治疗可改善成年大鼠脑梗死后的神经功能,并促进梗死灶周围的血管发生,SDF-1/CXCR4信号通路可能在脑梗死后血管发生过程中起重要的调控作用.
目的 探討外源性基質細胞衍生因子-1α(stromal cell-derived factor-1α,SDF-1 α)對大腦皮質跼竈性梗死成年大鼠梗死竈週圍血管髮生的影響及其可能機製.方法 24隻雄性成年Sprague-Dawley大鼠隨機分為假手術組、SDF-1α治療組、溶劑對照組和SDF-1α+ CXCR4拮抗劑組,每組6隻.採用右側大腦中動脈皮質支永久閉塞+雙側頸總動脈暫時夾閉法製作大腦皮質跼竈性梗死模型.SDF-1α治療組和溶劑對照組分彆自右側大腦中動脈皮質支閉塞後1h起經側腦室註射SDF-1α(1μg/d)或等體積生理鹽水,連續6d;SDF-1α+CXCR4拮抗劑組自SDF-1α註射前皮下註射CXCR4拮抗劑AMD3100(1 mg/d),連續6d.所有大鼠處死前經腹腔註射5-溴脫氧尿嘧啶覈苷(5-bromo-2-deoxyuridine,BrdU)標記新增殖細胞.在模型製作後7d時行神經功能評分後處死各組大鼠,利用免疫熒光染色法檢測梗死竈週圍或假手術竈週圍的血管密度、新生血管內皮細胞數目及CXCR4+細胞錶達情況.結果 在造模後7d時,SDF-1α治療組神經功能評分較溶劑對照組和SDF-1α+ CXCR4拮抗劑組顯著改善(P均＜0.01).假手術組、溶劑對照組、SDF-1α組和SDF-1α+CXCR4拮抗劑組大鼠梗死竈週圍血管密度分彆為2.1±0.3％、7.0±0.3％、10.0±0.9％和7.1±0.3％(F=232.469,P＜0.001),假手術組顯著性低于SDF-1α組(P＜0.001),SDF-1α組顯著性高于溶劑對照組(P =0.002)和SDF-1α+ CXCR4拮抗劑組(P=0.001).假手術組、溶劑對照組、SDF-1α組和SDF-1 α+CXCR4拮抗劑組大鼠梗死竈週圍BrdU+/層黏蛋白+細胞數量分彆為21.7±3.1、79.7±6.0、176.0± 12.5和90.3±6.9(F=391.550,P＜0.001),假手術組顯著性少于SDF-1α組(P＜0.001),SDF-1α組顯著性多于溶劑對照組和SDF-1α+CXCR4拮抗劑組(P均＜0.001).溶劑對照組、SDF-1α組和SDF-1α+CXCR4拮抗劑組大鼠梗死竈週圍CXCR4+細胞數量分彆為59.3±4.5、120.3 ±13.9和62.9±5.9(F=85.052,P＜0.001),SDF-1α組顯著性多于溶劑對照組和SDF-1α+CXCR4拮抗劑組(P均＜0.001).結論 SDF-1α治療可改善成年大鼠腦梗死後的神經功能,併促進梗死竈週圍的血管髮生,SDF-1/CXCR4信號通路可能在腦梗死後血管髮生過程中起重要的調控作用.
목적 탐토외원성기질세포연생인자-1α(stromal cell-derived factor-1α,SDF-1 α)대대뇌피질국조성경사성년대서경사조주위혈관발생적영향급기가능궤제.방법 24지웅성성년Sprague-Dawley대서수궤분위가수술조、SDF-1α치료조、용제대조조화SDF-1α+ CXCR4길항제조,매조6지.채용우측대뇌중동맥피질지영구폐새+쌍측경총동맥잠시협폐법제작대뇌피질국조성경사모형.SDF-1α치료조화용제대조조분별자우측대뇌중동맥피질지폐새후1h기경측뇌실주사SDF-1α(1μg/d)혹등체적생리염수,련속6d;SDF-1α+CXCR4길항제조자SDF-1α주사전피하주사CXCR4길항제AMD3100(1 mg/d),련속6d.소유대서처사전경복강주사5-추탈양뇨밀정핵감(5-bromo-2-deoxyuridine,BrdU)표기신증식세포.재모형제작후7d시행신경공능평분후처사각조대서,이용면역형광염색법검측경사조주위혹가수술조주위적혈관밀도、신생혈관내피세포수목급CXCR4+세포표체정황.결과 재조모후7d시,SDF-1α치료조신경공능평분교용제대조조화SDF-1α+ CXCR4길항제조현저개선(P균＜0.01).가수술조、용제대조조、SDF-1α조화SDF-1α+CXCR4길항제조대서경사조주위혈관밀도분별위2.1±0.3％、7.0±0.3％、10.0±0.9％화7.1±0.3％(F=232.469,P＜0.001),가수술조현저성저우SDF-1α조(P＜0.001),SDF-1α조현저성고우용제대조조(P =0.002)화SDF-1α+ CXCR4길항제조(P=0.001).가수술조、용제대조조、SDF-1α조화SDF-1 α+CXCR4길항제조대서경사조주위BrdU+/층점단백+세포수량분별위21.7±3.1、79.7±6.0、176.0± 12.5화90.3±6.9(F=391.550,P＜0.001),가수술조현저성소우SDF-1α조(P＜0.001),SDF-1α조현저성다우용제대조조화SDF-1α+CXCR4길항제조(P균＜0.001).용제대조조、SDF-1α조화SDF-1α+CXCR4길항제조대서경사조주위CXCR4+세포수량분별위59.3±4.5、120.3 ±13.9화62.9±5.9(F=85.052,P＜0.001),SDF-1α조현저성다우용제대조조화SDF-1α+CXCR4길항제조(P균＜0.001).결론 SDF-1α치료가개선성년대서뇌경사후적신경공능,병촉진경사조주위적혈관발생,SDF-1/CXCR4신호통로가능재뇌경사후혈관발생과정중기중요적조공작용.
Objective To investigate the effect of exogenous stromal cell-derived factor-1 α (SDF-1 α) on angiogenesis peri-infarct region in cerebral cortex in adult rats and its possible 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-1 α (1 μg/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-1 α in the SDF-1 α + 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),SDF-1 α group significantly higher than both groups of solvent control (P =0.002) and SDF-1oα + CXCR4 antagonist (P =0.001).The numbers of BrdU+/laminin+ cells in the peri-infarct regions in the groups of sham operation,solvent control,SDF-1α treatment,and SDF-1α + CXCR4 antagonist were 21.7 ± 3.1,79.7 ± 6.0,176.0 ± 12.5 and 90.3 ± 6.9,respectively (F=391.550,P＜0.001),and that in the sham operation was significantly less than that in the SDF-1 α group (P ＜ 0.001),SDF-1 α group was significantly more than both groups of solvent control and SDF-1 oα + CXCR4 antagonist (all P ＜0.001).The numbers of CXCR4 + cells in the peri-infarct regions in the groups of solvent control,SDF-1α treatment,and SDF-1α+ CXCR4 antagonist were 59.3± 4.5,120.3 ± 13.9 and 62.9 ± 5.9,respectively (F =85.052,P ＜ 0.001),and that in SDF-1α group was significantly more than those in the both groups of solvent control and SDF-1 α + CXCR4 antagonist (all P ＜ 0.001).Conclusions SDF-1α treatment may improve the neurological function after focal infarction in the cerebral cortex in adult rats and promote angiogenesis in peri-infarct region.The SDF-1/CXCR4 signal pathway may play an important regulatory role in the process of angiogenesis after cerebral infarction.
