自体外周血内皮祖细胞移植联合PPAR激动剂治疗大鼠急性心肌梗死的实验研究

目的探讨自体外周血内皮祖细胞（EPCs）移植联合PPAR激动剂罗格列酮、非诺贝特治疗大鼠急性心肌梗死的可行性和疗效。方法40只SD雄性大鼠随机分为四组：心肌梗死对照组（组Ⅰ）、单纯EPCs移植组（组Ⅱ）、EPCs移植联合罗格列酮治疗组（组Ⅲ）、内皮祖细胞移植联合非诺贝特治疗组（组Ⅳ），每组10只。应用密度梯度离心法获得大鼠外周血单个核细胞，体外培养扩增获得较纯的EPCs后，移植到大鼠急性心肌梗死模型梗死区，罗格列酮组、非诺贝特组分别以罗格列酮（20mg·kg^-1·d^-1）和非诺贝特（20mg·kg^-1·d^-1）灌胃。8周后超声心动图检测大鼠心功能改变，测定血流动力学指标，免疫组化观察心肌内移植EPCs及大鼠心肌修复情况。结果细胞移植8周后，组Ⅱ、组Ⅲ和组Ⅳ大鼠心功能，左室收缩舒张功能较组Ⅰ明显改善（P〈0．05），且组Ⅲ和组Ⅳ改变更显著（P〈0．05）。结论EPCs移植可以显著改善急性心肌梗死大鼠的心功能，EPCs移植联用罗格列酮和非诺贝特，优于单独应用EPCs移植。

Treatment of acute myocardial infarction with autologous peripheral blood EPCs transplantation combined with PPAR agonist in rats

Objective To investigate the feasibility and therapeutic effect of autologous peripheral blood endothelial progenitor cells （EPCs）transplantation combined with agonist of peroxisome proliferators-activated receptor（ PPAR）, i. e. rosiglitazone and fenofibrate, in rats with acute myocardial infarction. Methods All SD rats（ n = 40）were randomly divided into myocardial infarction control group （group 1 ）, single EPCs transplantation group（ group 2）, EPCs transplantation combined with rosiglitazone group （group 3 ）and EPCs transplantation combined with fenofibrate group（group 4, each n = 10）. The method of density gradient centrifugation was used to collect single nucleus from peripheral blood, which were cultured and amplified in vitro, and then more pure EPCs were collected and transplanted to the infarction area in rat model of myocardial infarction. Group 3 and 4 were given orally rosiglitazone （ 20 mg·kg^-1·d^-1 ） and fenofibrate （20 mg·kg^-1·d^-1 ） respectively. After 8 weeks,the changes of rat heart function and hemodynamics indexes were determined by using ultrasound cardiogram（ UCG）, and the states of EPCs transplantation and myocardium repair were observed by using immunohistochemistry. Results After 8 weeks the left ventricular regional systolic and diastolic function in group 2,3 and 4 were improved significantly than those in group 1 （P 〈0.05 ）, and those was more significant in group 3 and 4 （P 〈 0. 05 ）. Conclusion EPCs transplantation can improve significantly the heart function in rats with acute myocardial infarction. The effect of EPCs transplantation combined with rosiglitazone or fenofibrate is better than that of only EPCs transplantation.