XIAP修饰的脂肪间充质干细胞在心肌梗死治疗中的作用

XIAP modified adipose-derived stem cells improve cardiac function following myocardial infarction

目的探讨XIAP修饰的脂肪间充质干细胞（ADMSCs）是否具有更强的活力，能否更好地恢复心功能，及基因修饰干细胞治疗模式的可行性。方法10周的雄性SD大鼠，体质量200—300g，取其腹股沟处脂肪组织，提取脂肪间充质干细胞行体外培养扩增。应用电转染的方法将XIAP表达质粒导入脂肪干细胞内，进行基因修饰。另取61只sD大鼠，年龄和体质量同前，顺序编号，按照随机数字表法完全随机分为对照组（18只）、ADMSCs组（18只）、XIAP修饰ADMSCs组（18只）和未处理组（7只）。结扎大鼠冠状动脉左前降支，选取梗死中央及边缘区共5个注射点，按分组每点注射生理盐水、ADMSCs悬液或经XIAP修饰的ADMSCs悬液或不做任何处理。结果注射4周后，同对照组相比，ADMSCs组的左心室射血分数明显改善[（0．57±0．05）对（0．53±0．03），P〈0．05]，心肌梗死面积百分比显著减小[（5．17±2．03）对（10．62±3．50），P〈0．05]；与ADMSCs组相比，XIAP修饰的ADMSCs对心肌梗死的治疗作用更为明显，射血分数0．64±0．03，心肌梗死面积百分比3．26±0．95，P〈0．05。结论ADMSCs能有效恢复梗死后心功能；XIAP修饰的ADMSCs在移植区的生存效率更高，能更好的恢复心功能。

Objective We want to study the therapeutic efficiency of autologous ADMSC transplantation in myocardial infarction. And we try to find out a good way to improve the therapeutic efficiency by using the combination of gene therapy andcell therapy. Anti-apoptotic protein XIAP was selected to fight against the ischemic environment of myocardic infaction. Methads ADMSC was isolated from rat inguinal fat tissue. ADMSC was cultivated with DMEM. XIAP experession plasmid waselertco-transduced to ADMSC. The anti-apototic function of XIAP was tested by serum stavation induced apotosis. The method of ligation of the left anterior descending artery was used to prepare the Myocardial infarction model. Then rats were randomlyseparated into three groups to receive direct epicardial injections of normal saline, or ADMSCs cell suspension or XIAP modified ADMSCs cell suspension at five sites in central zones of myocardial infarction and border zone. Cardiac function and the infarctsize were evaluated 4 weeks after ADMSCs transplantation. Results West blotting suggest that, XIAP over-expression block serum starvation induced apotosis. It showed that there are significant statistic difference among XIAP modified ADMSC trans-plantation group, ADMSC transplantation group and control group 4 week＇s after myocardial infarction （ P 〈 0.05）. Left ventric- ular ejection fraction（LVEF） shgwed a significant improvement in ADMSCs transplantation group compared to control group（P 〈 0.05 ）. Left ventricular end systolic diameter（ LVDs ） and left ventricular end diastolic diameter（ LVDd ） of ADMSCs group were smaller than control group （P 〈 0.05 ）. The area of myocardial infarction was significantly reduced in the ADMSCstransplantation group compared to the saline group （P 〈 0.05 ）. Compared to ADMSCs transplantation group, effect of the XI- AP modified ADMSC in rats with myocardial infarction is more obvious. The reduction of LVEF of XIAP modified ADMSCsgroup was significantly lower（9% ） than the ADMSCs group（ 16% ） （ P 〈 0.01 ）. Infarction area in XIAP modified ADMSCs group（3.26 ±0.95）% was smaller than ADMSCs group（5.17 ±2.03）% （P 〈0.05）. Conclusion Autologus ADMSCtransplantation is an efficient therapeutic tool in myocardial infarction therapy. Over expression of XIAP can partly inhibit lowserum induced apotosis of ADMSC in vitro, and it can improve left ventricular function better in vivo. Over expression XIAP of ADMSC can improve the therapeutic efficiency compare to ADMSC transplantation.