摘要
目的探讨基质细胞衍生因子-1α(SDF-1α)/CXCR4信号通路在缺氧培养骨髓内皮祖细胞(HEPCs)心肌内移植治疗缺血性心脏病中的生物学效应。方法从同种系成年雄性Wistar大鼠长骨中获取骨髓内皮祖细胞(EPCs),常规培养4d后,1%O2+5%CO2+94%N2培养3d。观察HEPCs对细胞因子100μg/LSDF-1α的迁移能力变化,蛋白印迹法观察HEPCs表面SDF-1α受体CXCR4表达。将同种系成年雄性Wistar大鼠26只,随机分为对照组(n=8),常规组(n=9)和缺氧组(n=9),建立急性心肌梗死模型,在心肌梗死边缘5个不同区域心肌内分别注射PBS溶液200μL,EPCs2×106个,HEPCs2×106个,4周后用心脏超声分析血流动力学和心脏功能变化。结果 HEPCs与EPCs相比,细胞对SDF-1α迁移能力明显增强,细胞表面SDF-1α受体CXCR4表达增加。HEPCs心肌内移植4周后心脏超声示,与常规组和对照组比较,缺氧组左室收缩末期内径和射血分数得到明显改善(均P<0.05);与对照组比较,缺氧组和常规组左室舒张末期内径明显改善(均P<0.05);而缺氧组和常规组左室舒张末期内径比较,改善不明显(P>0.05)。结论 HEPCs上调细胞表面CXCR4,通过SDF-1α/CXCR4信号通路介导EPCs增强发挥细胞生物学功效。调节SDF-1α/CXCR4信号通路是优化EPCs移植治疗缺血性心脏病的有效方法。
Objective To investigate the role of stromal cell-derived factor-la（SDF-lc0/CXCR4 signal pathway in the therapeutic effects of hypoxic preconditioning endothelial progenitor cell （HEPC） transplantation on acute myocardial infarction Methods Bone marrow endothelial progenitor cells （EPCs） were isolated from syngeneic adult male Wistar rats. EPCs were cultured under normoxic condition for 4 days and 1% 02＋5%CO2＋94%N2 condition for 3 days. The effect of HEP- Cs on the migration ability of 100 μg/L SDF-I was observed. Western blot assay was used to detect the expression of CX- CR4, the solo receptor of SDF-la on ceils surface. Then, 26 syngeneic adult male Wistar rats were randomized into 3 groups： control group （n=8）, EPCs group （n=9） and HEPCs group （n=9）. The acute myocardium infarction animal model was established. At infarction, the rats received 5-points peri-infarct intramyocardial injections of PBS 200 μL, 2x 10^6 EPCs and 2 x 10^6 HEPCs. After 4 weeks, the haemodynamics parameters of cardiac function were analyzed by echocardiography. Results Compare with EPCs, the migration ability of HEPCs towards SDF-la was increased significantly. The result of Western blot analysis showed an increased CXCR4 expression on the cell surface. After 4 weeks of transplantation, the left ventricular end systolic diameter and ejection fraction （EF%） were much improved in HEPCs group than those of EPCs group and control group （P 〈 0.05）. Compare with control group, the left ventricular end-diastolic diameter was significantly im proved in EPCs and HEPCs groups （P 〈 0.05）. There was no significant difference in the improvement of the left ventricular end-diastolic diameter between HEPCs and EPCs groups （P〉 0.05）. Conclusion SDF-lodCXCR4 pathway was up-regu- lated by HEPCs, which showed the therapeutic effects via EPCs. The adjustment of SDF-lcdCXCR4 signaling pathway is an effective method for the treatment of ischemic heart diseases.
出处
《天津医药》
CAS
北大核心
2013年第7期679-681,I0003,共4页
Tianjin Medical Journal
基金
天津市自然科学基金资助项目(项目编号:12JCYBJC33100)
关键词
受体
干细胞移植
内皮细胞
骨髓细胞
心肌梗死
缺氧
趋化因子
基质细胞衍生因子-1Α
receptors, CXCR4
stem cell transplanta-tion
endothelial cells
bone marrow cells
myocardial infarction
anoxia
chemokine CXCL12
stromal cell derived factor-1
