谈红，孟楠，张夏晓，苏莉，张国明，李晓燕，公雪，陈英剑，姜蕴珊

基础与实验研究

不同剂量培哚普利对兔急性心肌梗死后循环血内皮祖细胞动员作用

谈红，孟楠，张夏晓，苏莉，张国明，李晓燕，公雪，陈英剑，姜蕴珊

目的：研究不同剂量培哚普利对兔急性心肌梗死（AMI）后循环血中内皮祖细胞（EPCs）数量的影响，及循环血血浆中血管内皮生长因子（VEGF）、血管紧张素Ⅱ（AngⅡ）及血管紧张素1～7（Ang1～7）含量的变化。

方法：选择清洁级（2.2±0.3）kg新西兰大白兔，开胸及部分结扎左前降支处理，将存活的实验用兔随机分为四组，A组为假手术组（n=7)；B组为AMI组（n=6)；C组为小剂量培哚普利组（n=6)；D组为大剂量培哚普利组（n=6)。分别于1、3、7、14、28天采血，用流式细胞仪计数循环血中内皮祖细胞（EPCs）的数量，酶联免疫吸附法（ELISA）检测循环血中VEGF、AngⅡ、Ang1～7的含量。

结果：AMI后，四组外周循环血中EPCs数量、VEGF的含量随着时间的推移均逐渐增加，于第7天达到高峰，之后逐渐降低，D组上述趋势变化最明显，且28天时D组较B组、C组仍能维持在较高水平[EPCs：（0.066±0.005）% vs （0.059±0.005）%，（0.062±0.003）%；VEGF（114.692±9.599）pg/ml vs（84.058±4.608）pg/ml， （102.570±10.869）pg/ml] ，差异均有统计学意义（P均＜0.05)；四组AngⅡ的含量增多，于第3天达到高峰，之后逐渐下降，下降幅度以D组最为明显；Ang1～7在手术组第1天有明显下降趋势，之后逐渐增多，随着时间推移呈逐渐增多的趋势，以D组更为明显。

结论: 培哚普利可促进AMI兔外周循环血中EPCs的动员及VEGF、Ang1～7含量的增多，降低 AngⅡ的水平，且应用大剂量培哚普利干预效果更明显。

心肌梗死；内皮祖细胞；培哚普利

Objective: To study different doses of perindopril on circulating blood endothelial progenitor cells (EPCs) mobilization and the levels of vascular endothelial growth factor (VEGF), angiotensin II (AngII), angiotensin 1-7 (Ang1-7) in rabbit model of acute myocardial infarction (AMI).

Methods: AMI model was established in New Zealand white rabbits by partial ligation of left anterior descending artery, the mean body weight of animal was (2.2±0.3) kg. Surviving rabbits were divided into 4 groups: ①Sham operation group, n=7, ②AMI group, n=6, ③AMI+small dose of perindopril group, n=6 and ④AMI+large dose of perindopril group, n=6. Peripheral blood was taken at 1, 3, 7, 14, 28 days of AMI, blood levels of EPCs were examined by fow cytometry; VEGF, AngII and Ang1-7 were measured by ELISA.

Results: Within 4 weeks of AMI, blood levels of EPCs, VEGF were increasing in all 4 groups, they reached the peakat day-7 followed by gradually decreasing, the most obvious trend was in Group④. Compared with Groups②, ③, at day-28 of AMI, Group④ had the higher levels of EPCs (0.066±0.005) % vs (0.059±0.005) %, (0.062±0.003) % and VEGF (114.692±9.599) pg/ml vs (84.058±84.608) pg/ml, (102.570±10.869) pg/ml, all P＜0.05. AngII level was elevated after AMI, its reached the peak at day-3 followed by gradually decreasing, the most obvious reduction was in Group④. Ang1-7 level presented obvious decreasing trend at day-1 followed by gradually increasing; in Groups③, ④, it was initially reduced and as time went on, the trend had been increasing especially in Group④.

Conclusion: Perindopril may promote EPCs mobilization, increase blood levels VEGF, Ang1-7 and decrease AngII in rabbit model of AMI; such effects were more obvious in large dose of perindopril intervention.

(Chinese Circulation Journal, 2016,31:1120.)

心血管疾病已经成为发达国家的“第一杀手”，其中又以急性心肌梗死（AMI）最为严重，给患者带来极大威胁，严重影响了患者生存质量。……