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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2016年第2期

页码:

139-144

栏目:

基础研究

出版日期:

2015-11-25

文章信息/Info

Title:

Effects of recombinant adeno-associated virus vector co-expressing PR39 and ADM in treatment of myocardioal infarction in rats

作者:

安 睿¹; 席 聪²; 李海勋¹; 申国宏³; 张淑苗⁴; 王跃民⁴; 孙立军¹

(第四军医大学：1.西京医院放射科，4.基础部生理学教研室，陕西 西安 710032；
2.宝鸡市人民医院神经内科，陕西 宝鸡 721000；
3.武警山西省总队医院综合科，山西 太原 030006)

Author(s):

AN Rui¹;  XI Cong²;  LI Hai-xun¹;  SHEN Guo-hong³;  ZHANG Shu-miao⁴;  WANG Yue-min⁴;  SUN Li-jun¹

(1.Department of Radiology, Xijing Hospital, 4.Department of Physiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China；

2.Department of Neurology, Baoji People’s Hospital, Baoji 721000, Shaanxi, China；

3.Integrated Branch, Hospital of Shanxi Armed Police Corps, Taiyuan 030006, Shanxi, China)

关键词:

心肌梗死; 基因治疗; 抗菌肽; 肾上腺髓质素

Keywords:

myocardial infarction;  gene therapy;  antimicrobial peptide;  adrenomedullin

分类号:

R542.2

DOI:

-

文献标识码:

A

摘要:

目的 探讨以腺相关病毒（adeno-associated virus,AAV）作为载体的抗菌肽PR39与肾上腺髓质素（adrenomendullin,ADM）双基因共表达产物（rAAV-PR39-ADM）对大鼠心肌梗死的防治作用。方法 冠状动脉左前降支结扎建立心肌梗死（myocardial infarction,MI）模型。将雄性SD大鼠分为Sham组（假手术），生理盐水组（MI+NS），空病毒组（MI+AAV-GFP）和治疗组（MI+rAAV-PR39-ADM）。各组大鼠手术4周后行B型超声、血流动力学检测心功能，心脏病理染色计算梗死面积和胶原容积分数，免疫荧光检测可以间接代表PR39和ADM表达的标签肽6His-Tag，Western blot检测6His标签肽以及血管内皮生长因子 (vascular endothelial growth factor,VEGF)蛋白表达。结果 B超及血流动力学指标显示治疗组射血分数（ejection fraction,EF）和各项心功能指标较生理盐水与空病毒组明显改善，MI面积明显减小（P<0.05）；且标签肽以及VEGF蛋白表达量高于空病毒组与生理盐水组（P<0.05）。结论 rAAV-PR39-ADM具有明显改善MI大鼠的心脏功能、减少MI面积，促进血管生成的作用。

Abstract:

AIM To investigate an innovatively designed gene expression product, rAAV-PR39-ADM, which was mediated by recombinant adeno-associated virus co-expressing antimicrobial peptide (PR39) and adrenomedullin (ADM) in the treatment of myocardial infarction (MI). METHODS Rats were randomly divided into sham group, normal saline group (MI+NS), blank adeno-associated virus vector group (MI+AAV-GFP) and treatment group (MI+rAAV-PR39-ADM). MI model was established by ligation of left coronary artery. On the fourth week after modeling, echocardiography and hemodynamics methods were employed to assess the cardiac functions. Infarct size and collagen volume fraction were calculated by pathological staining, 6His-Tag which indirectly represented the expression of PR39 and ADM was tested by immunochemistry, and 6His-Tag and VEGF expressions were measured by Western blot. RESULTS It was found that the cardiac functions were significantly improved and the infarct size was significantly decreased in treatment group. 6His-Tag and VEGF in treatment group were significantly higher than those in MI+NS group and MI+AAV-GFP group (P<0.05). CONCLUSION rAAV-PR39-ADM significantly improves the cardiac functions after myocardial infarction, attenuates the infarct size and promotes angiogenesis.

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备注/Memo

备注/Memo:

收稿日期：2015-01-30.
基金项目：国家自然科学基金项目（81170185）
通讯作者：孙立军，教授，主要从事基因对心肌缺血性疾病的保护性研究 Email:slj@fmmu.edu.cn
作者简介：安睿，硕士生 Email：atczln@163.com

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更新日期/Last Update: 2016-04-25