经静脉或冠脉移植脐带间充质干细胞治疗猪急性心肌梗死实验研究

发布时间：2018-06-19 21:39

本文选题：脐带间充质干细胞 + 移植　；参考：《天津医科大学》2013年硕士论文

【摘要】：目的：观察经静脉或冠脉移植脐带间充质干细胞(mesenchymal stem cells, MSCs)对急性心肌梗死猪的心功能、梗死面积、新生毛细血管数量的影响。方法：实验于2011年1月至2012年6月在泰达国际心血管病医院动物实验室在用球囊封堵前降支制作急性心肌梗死模型。造模成功并完成干细胞移植的23只猪分为3组：冠脉组8只,静脉组8只,对照组7只。移植组于心肌梗死后2周分别经静脉和冠脉的方式移植干细胞,对照组经静脉注射等量的生理盐水。所有实验猪分别于干细胞移植前和移植后6周行超声心动图检查,测量左室舒张末容积(LVEDV).左室收缩末容积(LVESV)、左心室射血分数(LVEF)、短轴缩短率(FS)；所有实验猪分别于干细胞移植前和移植后6周行心肌核素灌注显像检查,计算左室梗死面积及梗死质量比；移植后6周时,氯化钾注射法处死猪,分别取梗死区、梗死周边区心肌,行vWF免疫组化染色,计算毛细血管密度。并行透射电镜观察细胞移植后分化情况。结果： 1.与对照组相比,静脉移植组和冠脉移植组的左室舒张末容积(LVEDV)、左室收缩末容积(LVESV)缩小、左室射血分数(LVEF)、短轴缩短率(FS)增加,差异具有统计学意义[冠脉组：56.86±7.62mm,16.25±6.45mm,71.25±8.94%,39.52±6.85%;静脉组：59.38±5.55mm,17.63±6.14mm,69.38±6.93%,38.25±6.69%;对照组：70.57±8.50mm,25.57±7.55mm,59.71±7.18%,31.29±5.19%;(P0.05)]。冠脉移植组与静脉移植组比较,无明显差异(P0.05)。 2.与对照组相比,冠脉组和静脉组的左室心肌梗死面积、梗死质量比明显缩小,差异具有统计学意义[冠脉组：15.13±2.99%,16.13±2.99%；静脉组：13.13±3.23%,15.00±3.07%；对照组：21.43±5.88%,22.86±6.49%；(P0.05)]。冠脉组与静脉组间无显著性差异(P0.05)。 3.与对照组相比,冠脉组和静脉组的新生毛细血管的数量明显增加,差异具有统计学意义[冠脉组：14.71±2.99个；静脉组：13.58±2.65个；对照组：10.24±1.71个；(P0.05)]。冠脉组与静脉组间无显著性差异(P0.05)。 4.移植组脐带间充质干细胞可分布于梗死区及梗死周边区,透射电镜下可见由干细胞分化而来的的血管内皮细胞及心肌样细胞。结论：经静脉或冠脉两种途径移植脐带MSCs均能有效地改善急性心肌梗死猪的心功能,缩小左室舒张末期容积和收缩末期容积,缩小梗死面积,增加毛细血管的数量,两种途径之间无显著的差异。
[Abstract]:Aim: to investigate the effects of mesenchymal stem cells (MSCs) on cardiac function, infarct size and the number of new capillaries in acute myocardial infarction (AMI) pigs. Methods: from January 2011 to June 2012, the model of acute myocardial infarction was established in the animal laboratory of Taida International Cardiovascular Hospital. The 23 pigs were divided into 3 groups: coronary group (n = 8), vein group (n = 8) and control group (n = 7). Stem cells were transplanted by vein and coronary artery two weeks after myocardial infarction in the transplantation group and the control group were injected with the same amount of physiological saline via vein. The left ventricular end-diastolic volume (LVEF) was measured by echocardiography before and 6 weeks after stem cell transplantation. Left ventricular end-systolic volume (LVEF), left ventricular ejection fraction (LVEF), short axis shortening rate (STR) and myocardial radionuclide perfusion imaging were performed before and 6 weeks after transplantation to calculate the infarct size and infarct mass ratio of the left ventricle. The pigs were killed by potassium chloride injection. The infarcted and peri-infarcted myocardium were taken respectively and the capillary density was calculated by using vWF immunohistochemical staining. The cell differentiation after transplantation was observed by transmission electron microscope. Results: 1. Compared with the control group, left ventricular end-diastolic volume (LVEF), left ventricular end-systolic volume (LVESVV), left ventricular ejection fraction (LVEF) and short axis shortening rate (FSs) were decreased in vein transplantation group and coronary artery transplantation group. The difference was statistically significant [56.86 卤7.62mm 卤16.25 卤6.45mm in the coronary group 71.25 卤8.94 in the coronary group, 39.52 卤6.85mm in the venous group; 59.38 卤5.55mm in the venous group, 69.38 卤6.93mm in the venous group, 38.38 卤6.93mm in the control group; 70.57 卤8.50mm / 25.57 卤7.55mm / 25.57 卤7.55mm / 59.71 卤7.18mm in the control group, 31.29 卤5.195mm respectively]. There was no significant difference between the coronary artery transplantation group and the vein transplantation group. Compared with the control group, the myocardial infarction size and the infarct mass ratio of the coronary artery group and the vein group were significantly reduced, and the difference was statistically significant [the coronary artery group: 15.13 卤2.99g; the venous group: 13.13 卤3.23g 15.00 卤3.07; the control group 21.43 卤5.880.86 卤6.49P 0.05]. There was no significant difference between the coronary artery group and the venous group. Compared with the control group, the number of neocapillaries in the coronary artery group and the venous group was significantly increased, with statistical significance [the coronary artery group: 14.71 卤2.99; the venous group: 13.58 卤2.65; the control group: 10.24 卤1.71 (P0.05)]. There was no significant difference between the coronary artery group and the venous group. The umbilical cord mesenchymal stem cells in the transplantation group could be distributed in the infarcted and peri-infarction areas. Vascular endothelial cells and cardiomyocyte-like cells differentiated from stem cells could be seen under transmission electron microscope. Conclusion: transplantation of umbilical cord MSCs via vein or coronary artery can effectively improve cardiac function, reduce left ventricular end-diastolic volume and end-systolic volume, reduce infarct area and increase the number of capillaries in acute myocardial infarction pigs. There was no significant difference between the two approaches.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R542.22

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