Effect of gene modified mesenchymal stem cells overexpression human receptor activity modified protein 1 on inflammation and cardiac repair in a rabbit model of myocardial infarction
10.3760/cma.j.issn.0253-3758.2012.09.004
- VernacularTitle:人受体活性修饰蛋白1基因修饰间充质干细胞调节兔心肌梗死后炎症及对其心脏修复的作用
- Author:
Ran-Zun ZHAO
1
;
Xian-Ping LONG
;
Zhi-Jiang LIU
;
Dong-Mei WANG
;
Bei SHI
Author Information
1. 遵义医学院第一附属医院
- Keywords:
Myocardial infarction;
Mesenchymal stem cells;
Inflammation;
Receptor activity modified protein-1
- From:
Chinese Journal of Cardiology
2012;40(9):736-741
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of mesenchymal stem cells (MSCs) overexpressing human receptor activity modified protein 1 (hRAMP1) by adenovirus vector on infarction related inflammation and cardiac repair in a rabbit model of myocardial infarction (MI).Methods Thirty rabbits underwent coronary artery ligation for 60 minutes followed by 24 hours reperfusion and divided into MSChRAMP1 group (intravenously injection of MSCs transfected with adenovirus vector encoding hRAMP1 gene enhanced green fluorescent protein,EGFP,n =10),MSCnull group (MSCs transfected with adenovirus vector encoding only EGFP without hRAMP1 gene,n =10) and control group (equally volume of phosphate buffered saline,PBS,n =10).The plasma level of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were quantified by ELISA assay at before and 1,3,7,28 days after induction of MI.The expression of nuclear factor-κB (NF-κB) and hRAMP1 in infracted myocardium were measured by Western blot at 1,3,7,28 day following MI.The area of MI and collagen deposition and fibrosis were evaluated by TTC staining and Masson staining,respectively.Results Area of MI and collagen content were significantly reduced in MSChRAMP1 group compared those in MSCnull and control group [ (10.1 ±2.9)％ vs.(30.6 ±2.7 )％ and (22.5 ±3.2)％,P ＜ 0.05 ].Myocardial expression of NF-κB and plasma TNF-α[ 7 days after transplantation:(97.2 ± 6.7) pg/ml vs.( 207.6 ± 12.7 ) pg/ml and ( 153.2 ± 9.9) pg/ml,P＜0.05 ]were also lower while plasma level of IL-10 [ 7 days after transplantation:(238.5 ± 17.5) pg/ml vs.(177.3±19.8) pg/ml and (244.6 ±27.3) pg/ml,P＜0.05] was significantly higher in MSChRAMP1 group than in MSCnull and control group.Conclusion MSCs overexpression hRAMP1 could further reduce area of MI possibly through inhibiting the myocardial expression of NF-κB and reducing the plasma TNF-α level and raising plasma IL-10 level.
