摘要
目的 观察同种异体骨髓间充质干细胞（MSCs）移植入受体后,基质细胞衍生因子1/趋化因子受体4（SDF-1/CXCR4）轴在促进SD大鼠急性心肌梗死心脏功能恢复中的作用.方法 96只雄性SD大鼠随机分为MSCs组（MSCs移植）、单纯心梗组、假手术组,每组各32只.MSCs组和单纯心梗组结扎SD大鼠冠状动脉左前降支造成急性心肌梗死10 min后,分别在梗死区域、梗死区边缘局部注射50μl MSCs（0.01＆#215;106个/μl,MSCs组）或注入相同容量生理盐水（单纯心梗组）;假手术组只做开胸.各组术前及术后28 d采用超声心动图测量左心室舒张末期内径（LVDd）、左心室收缩末期内径（LV Ds）、左室射血分数（EF）3项反应心脏功能的指标.术后l、7、14、28 d每组各处死8只大鼠取心脏组织作免疫组化、常规病理染色、心肌梗死面积、梗死区心室壁厚度和心室肌内微血管密度等项目检查.RT-PCR、免疫激光共聚焦定性及定量测定SDF-1/CXCR4在各组心肌组织内表达变化.结果 术后28 d时梗死区域、梗死区边缘心肌梗死面积MSCs组为：（22.5±2.4）％比（34.9±1.9）％,单纯心梗组为：（30.2±2.4）％比（35.5±2.8）％,组间差异均有统计学意义（均P＜ 0.05）;MSCs组、单纯心梗组左室前壁厚度分别为：（2.88±0.32）、（1.80±0.71）mm,组间差异有统计学意义（P＜0.05）.28 d时超声心动图结果显示,MSCs组LVDd、LVDs和EF分别为（26.23±0.40）、（17.00±0.81）mm和（41.33±6.02）％,单纯心梗组LVDd、LVDs和EF分别为（28.14±0.39）、（20.17±0.53）mm和（33.32±6.88）％,假手术组LVDd、LVDs和EF分别为（20.99±0.51）、（12.99±0.41） mm和（51.88±4.10）％,MSCs组和单纯心梗组与假手术组比较心功能均有显著下降（P＜0.05）,而MSCs组与单纯心梗组比较心功能有明显改善（P＜0.05）.MSCs组心肌梗死边缘区新生微血管（15.77±0.25）个/视野,单纯心梗组（5.67 ±0.15）个/视野,与假手术组[（8.70±0.63）个/视野]比较差异均有统计学意义（均P＜0.05）.MSCs、正常心肌组织和梗死心肌组织均有SDF-1/CXCR4表达.移植MSCs后SDF-1/CXCR4在梗死周边区域注射细胞处及局部血管壁高表达.SDF-1 mRNA、CXCR4 mRNA、SDF-1和CXCR4蛋白荧光强度在术后1、7、14、28 d时,MSCs组和单纯心梗组与假手术组比较有显著升高（P＜0.05）,MSCs组与单纯心梗组比较显著升高（P＜0.05）.结论 SD大鼠急性心肌梗死局部注射MSCs可显著提高SDF-1/CRCX4表达,同时心功能得到改善.SDF-1/CRCX4轴表达上调可能是MSCs移植改善心梗后心肌功能的重要途径。
Objective To explore the role of stromal cell derived factor-1 （SDF-1）/CXCR4 axis in acute infarct myocardium after an implantation of bone marrow mesenchymal stem cells （MSCs） in rats.Methods The animals were anesthetized by an intraperitoneal injection of pentobarbital sodium.Left anterior thoracotomy through 3/4 intercostals region was performed and then left anterior descending coronary arteries were ligated for modeling acute myocardial infarction.The MSCs were injected into the area of acute infarct myocardium after a 10-minute ligation of left anterior descending coronary artery.The different concentration and expression of SDF-1/CXCR4 in the area of acute myocardial infarction and left ventricular function were analyzed.Results At day 28 post-transplantation,the vascular density in MSCs implant group were significantly higher than that in control group（P 〈 0.05）.And left ventricular function in MSCs implant group improved significantly than that in control group too（P 〈 0.05）.At the same time,the expressions of SDF-1 and CXCR4 in topical injection sites of infarct myocardium were significantly higher than those in control group（P 〈 0.05）.In MSCs implant group,the level of SDF-1/CXCR4 peaked at Day 1 posttransplantation and then it declined.Conclusions After the implantation of MSCs into acute infarct myocardium,there is vascular regeneration and the level of SDF-1/CXCR4 increases so that left ventricular function improves.And the mechanism may be due to an up-regulation of SDF-1/CXCR4 axis.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2015年第18期1421-1424,共4页
National Medical Journal of China
基金
贵州省国际科技合作重点项目计划[黔科合外G字（2007）400120号]
