人尿液干细胞移植治疗大鼠心肌损伤

Human urine-derived stem cells transplantation for treatment of myocardial infarction in rats

背景:近年来多项研究已经显示骨髓间充质干细胞、脂肪干细胞、心肌干细胞等可以参与心肌修复,但是人尿源性干细胞在心肌梗死方面的研究还非常缺乏。目的:探讨人尿液干细胞移植对急性心肌梗死模型大鼠心功能的影响及其机制。方法:64只SD大鼠,随机取20只为正常对照组,余44只结扎冠状动脉左前降支制备急性心肌梗死模型,最终建模成功40只大鼠,随机分为心肌梗死组和人尿液干细胞移植组,每组20只,正常对照组和心肌梗死组尾静脉注射生理盐水,人尿液干细胞移植组尾静脉注射CM-Dil标记的人尿液干细胞,1次/d,连续3d。移植后6周,超声心动图检测大鼠心功能,然后取心肌组织行CD34免疫组化染色、苏木精-伊红染色、TUNEL染色、RT-PCR检测。结果与结论:(1)与心肌梗死组比较,人尿液干细胞移植组大鼠心功能明显改善(P <0.05),新生毛细血管密度增多(P <0.05),细胞凋亡率显著降低(P <0.05);(2)正常对照组和心肌梗死组大鼠心肌组织中没有CM-Dil阳性细胞,人尿液干细胞移植组大鼠心肌组织出现大量的CM-Dil阳性细胞;(3)与心肌梗死组相比,人尿液干细胞移植组心肌组织中Bcl-2基因表达显著增高(P <0.05),Caspase-3基因表达显著降低(P <0.05);(4)结果表明,人尿液干细胞移植对损伤心肌有明显的修复作用,能够减少心肌细胞凋亡,改善心肌梗死大鼠心功能。

BACKGROUND:In recent years,many studies have shown that bone marrow mesenchymal stem cells,adipose-derived stem cells,and cardiac stem cells can participate in myocardial repair,but little is reported on the use of human urine-derived stem cells in the treatment of myocardial infarction.OBJECTIVE:To investigate the effect of human urine-derived stem cell transplantation on the heart function of myocardial infarction rats.METHODS:The 20 of 64 Sprague-Dawley rats were selected as normal control group,and the remaining 44 rats were subjected to ligation of the left anterior descending coronary artery to make myocardial infarction models.The 40 model rats were successfully made and randomized into myocardial infarction group and cell transplantation group with 20 rats in each group.The rats in the myocardial infarction group were given injection of normal saline by tail vein,while those in the cell transplantation were given injection of human urine-derived stem cells labeled by CM-Dil by tail vein.The treatment was done once a day and lasted for 3 consecutive days.At 6 weeks after cell transplantation,the heart function of rats was examined by echocardiography,and the myocardial tissues of rats in each group were taken for CD34 immunohistochemical staining,hematoxylin-eosin staining,TUNEL staining and RT-PCR detection.RESULTS AND CONCLUSION:Compared with the myocardial infarction group,significantly improved heart function of rats,increased density of neonate blood capillaries,and decreased apoptotic rate were observed in the cell transplantation group(all P<0.05).The CM-Dil positive cells were not observed in the normal control group and myocardial infarction group,while a great number of positive cells appeared in the cell transplantation group.Compared with the myocardial infarction group,Bcl-2 gene expression level in the cell transplantation group was significantly higher(P<0.05),while the Caspase-3 gene expression level was lowered(P<0.05).In conclusion,transplantation of human urine-derived stem cells can significantly improve the heart function of rats with acute myocardial infarction,and reduce cell apoptosis in the rat myocardium.