腺病毒介导的基质细胞衍生因子-1对心肌梗死大鼠心脏功能的影响
Effect of adenovirus-mediated stromal cell-derived-factor-1 alpha gene transfer on heart function in myocardial infarction of rats
王杨 1张娟 1唐俊明 1杨建业 2王家宁 2孔霞 2郭凌郧 2郑飞 2黄永章2
作者信息
- 1. 郧阳医学院附属人民医院临床医学研究所,湖北,十堰,442000;郧阳医学院国际药护学院,湖北,十堰,442000;郧阳医学院生理学教研室,湖北,十堰,442000
- 2. 郧阳医学院附属人民医院临床医学研究所,湖北,十堰,442000
- 折叠
摘要
目的:探索腺病毒介导的基质细胞衍生因子-1对心肌梗死心脏功能的影响.方法:采用成年SD大鼠,经左冠状动脉前降支结扎建立急性心肌梗死模型.术后1 h,将1×1010PFU Adv-SDF-1分6个点注射到心肌梗死部位及其周边区域.移植后4 Wk测定心脏功能,随后取材、连续冰冻切片,观察CDl33和CD31的表达以及心肌组织形态学.结果:注射在心肌梗死部位的Adv-SDF-1高表达,促进了CD133和CD31阳性细胞迁移到心肌梗死部位,增加了心肌梗死部位毛细血管的密度(Ad-SDF-1组与模型组和Ad-LacZ组相比:32±4 VS15±2,16±3,P<0.05),保护并促进了心肌再生,从而缩小梗死区域面积,心室壁的厚度和弹性增加;心室胶原含量减少[Ad-SDF-1组与模型组和Ad-LacZ组相比:(41±3)%vs(78±8)%,(76±7)%,P<0.05],延缓心室重构而改善心脏的收缩和舒张功能.结论:SDF-1过表达通过促进血管新生改善心肌的血供,达到改善心脏功能的目的.
Abstract
AIM: To explore the effect of adenovirus-mediated stromal cell-derived-factor-1( Adv-SDF-1 ) alpha on angiogenesis and heart function of myocardial infarction in rats. METHODS: The animal model of myocardial infarction (MI) was established by occluding the rat left anterior descending arteries (LAD). 1×1010 PFU Adv-SDF-1 or 1×1010 PFU Ad-LacZ was immediately injected into the infarcted myocordium, and 200 μL cell-free PBS was injected into the infarcted region or the myocardial wall in control and sham group, respectively. Four weeks after injection, cardiac function was analyzed. Heart tissues were taken after the measurement of hemodynamics. Histological and morphometric measurement was performed by image analysis system and expressions of CD133 and CD31 were detected by immunofhorescent histochemistry. RESULTS: Significantly higher expression of Adv-SDF-1 was observed in the Adv-SDF-1 injected MI areas, which promoted CD133 and CD31 positive cells migrating into the infarcted hearts, enhanced the density of blood vessels, and contributed to the protection and regeneration of myocardium. Decreased infarct size, reduced collagen contents and thicker left ventricle wall were observed in Adv-SDF-1 group. These changes of structure in the infarcted hearts improved the systolic and diastolic function of the heart. CONCLUSION: The high expression of SDF-1 improves cardiac structure and function of MI through angiogenesis.
关键词
人基质细胞衍生因子-1/腺病毒科/心肌梗塞/新生血管化,病理性Key words
hSDF-1/adenoviridae/myocardial infarction/neovascularization, pathologic引用本文复制引用
基金项目
国家自然科学基金(30700306)
湖北省卫生厅重点项目(JX3829)
湖北省自然科学基金(2005ABA079)
湖北省教育厅重点项目B类(B200624006)
出版年
2009