内皮祖细胞动员对生理性缺血训练促进远隔缺血心肌侧支生成的作用研究

发布时间：2018-01-23 01:00

本文关键词： 生理性缺血训练心肌缺血侧支循环内皮祖细胞血管内皮生长因子　出处：《南京医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的：探讨EPCs动员在生理性缺血训练促进远隔缺血心肌侧支循环生成过程中的作用。方法：42只兔进行可控性心肌缺血造模,造模成功后随机分入以下6组：①假手术组(Sham-operated group, SO);②单纯生理性缺血训练组(Training only group,TO)；③单纯心肌缺血组(Myocardial ischemia group, MI);④生理性缺血训练组(Physiological ischemic training group, PIT);⑤阿托伐他汀组(EPC promotor group, PIT+);⑥雷帕霉素组(EPC inhibitor group, PIT-).生理性缺血训练共4周,每次3分钟,间隔5分钟,每周训练5天,每天训练3次；心肌缺血刺激共4周,每次2分钟,间隔10分钟,每周刺激5天,每天刺激2次。实验终点时,处死动物取材,进行实验室检测：ELISA法检测外周血中VEGF含量；Western blot法检测缺血心肌中VEGF表达；流式细胞术检测外周血和缺血心肌中EPCs数量；微球技术检测缺血心肌侧支循环血流量。考虑到各组VEGF蛋白含量、EPCs数量和冠状动脉侧支循环血流量的改变量的实验数据并不符合正态分布,因此本研究采用非线性分析方法来计算各组间的差异,同时使用盒须图来呈现统计结果。结果：4周PIT后,VEGF含量在PIT组和PIT+组显著增加,与SO组、TO组和MI组相比,外周血和缺血心肌中VEGF含量在PIT组显著增加,结果具有统计学意义。PIT+组的EPCs数量在外周血和缺血心肌中均显著高于其他各组,PIT组与其他各组相比,外周血EPCs数量的差异同样具有统计学意义。CCBF和CCBF/CBF在PIT+组和PIT组显著高于SO组、TO组和MI组。PIT-组的各项指标与SO组和TO组相比,差异均无统计学意义。EPCs数量的增加最高有43%可以被VEGF含量的增加解释,CCBF和CCBF/CBF的增加最高有90%可以被EPCs数量的增加解释。结论：PIT可促进EPCs动员,通过其远隔效应归巢到缺血心肌生成侧支循环,改善冠脉血流,最终实现“生物搭桥”；通过促进和抑制EPCs,证实EPCs在PIT介导的缺血心肌侧支循环生成过程中具有重要作用。
[Abstract]:Aim: to investigate the role of EPCs mobilization in physiological ischemic training to promote collateral circulation formation in distant ischemic myocardium. Methods Twenty two rabbits were induced by controlled myocardial ischemia and were randomly divided into the following 6 groups: the sham-operated group (SOP) and the sham-operated group (SOP). (2) training only group in physiologic ischemic training group; 3Myocardial ischemia group; 4Physiological ischemic training group; 5EPC promotor group, PIT group in Atto vastatin group; 6in rapamycin group, EPC inhibitor group, PIT-0.Physiologic ischemia training lasted for 4 weeks, 3 minutes each time, the interval was 5 minutes, 5 days per week. Training 3 times a day; Myocardial ischemia was stimulated for 4 weeks, 2 minutes each time, 10 minutes interval, 5 days a week, 2 times a day. At the end of the experiment, the animals were sacrificed. The content of VEGF in peripheral blood was detected by the method of Elisa. The expression of VEGF in ischemic myocardium was detected by Western blot method. The number of EPCs in peripheral blood and ischemic myocardium was detected by flow cytometry. Microsphere technique was used to measure the collateral circulation blood flow in ischemic myocardium. The experimental data of the number of VEGF and the changes of coronary collateral circulation blood flow were not in accordance with normal distribution considering the content of VEGF protein in each group. Therefore, the nonlinear analysis method is used to calculate the differences among groups, and the box chart is used to present the statistical results. Results after 4 weeks of PIT, the content of VEGF in PIT group and PIT group was significantly higher than that in so group and MI group. The content of VEGF in peripheral blood and ischemic myocardium was significantly increased in PIT group. The results showed that the number of EPCs in Pit group was significantly higher than that in other groups in peripheral blood and ischemic myocardium. Compared with other groups, the number of EPCs in peripheral blood of PIT group was significantly higher than that of so group. CCBF and CCBF/CBF in PIT group and PIT group were significantly higher than that in so group. Compared with so group and to group, the increase of the number of VEGF in to group and MI group could be explained by the increase of VEGF content. Up to 90% of the increase in CCBF and CCBF/CBF can be explained by the increase in the number of EPCs. Conclusion EPCs mobilization can be promoted by the effect of wet-pit, which can homing to collateral circulation of ischemic myocardium, improve coronary blood flow, and finally realize "biological bypass graft". By promoting and inhibiting EPCs, it is confirmed that EPCs plays an important role in the formation of collateral circulation in ischemic myocardium mediated by PIT.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R87

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