Effect and mechanism of BMSCs transfected with b FGF gene on reperfusion injury in rats with acute myocardial infarction
Wang Qian
Ren Lin
Zhang Pengyu
Li Fang
Yang Guifeng
Abstract：To observe the effects of bone marrow mesenchymal stem cells (BMSCs) transfected with basic fibroblast growth factor (b FGF) gene on reperfusion injury in rats with acute myocardial infarction (AMI) and to explore its mechanism. Method BMSCs were isolated and identified of rats in vitro and BMSCs transfected with b FGF plasmid were cultured. 40 SD rats were selected, and 30 of them were established AMI reperfusion model. The successfully modeled rats were randomly divided into 3 groups: model group (4 points of epicardial injection medium, 200 μl/point), BMSCs group (same amount of BMSCs injected in same sites), BMSCs+b FGF group (same amount of BMSCs transfected with the b FGF plasmid injected in same sites), and the remaining 10 rats were sham group (same amount of medium injected in same sites). The cardiac function, the levels of serum tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) were compared 4 weeks after surgery. After the rats were sacrificed, the cardiomyocyte apoptosis index (AI) was compared. The relative expressions of b FGF, matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase inhibitor-1 (TIMP-1) m RNA and protein and MMP-9/TIMP-1 values were compared. Result The primary BMSCs cultured on the third day of anchorage growth, which was polygonal or spindle-shaped, with different shapes. The third generation increased in volume, showing long shuttle rows and uniform size. The characteristic phenotypes of BMSCs were identified by immunofluorescence assay. The positive expression rates of CD90 and CD105 were 96.03% and 95.44%, respectively. CD34 and CD45 were negatively expressed, which accorded with the typical phenotype of BMSCs. The left ventricular end-diastolic diameter (LVIDd), end-systolic diameter (LVIDs), the levels of serum TNF-α, IL-1β, AI, the relative expressions of MMP-9 m RNA and protein, MMP-9/TIMP-1 values were compared between each 2 groups, and the results showed that the indexes of the sham group were the lowest, the BMSCs+b FGF group the second, the BMSCs group slightly higher, the model group highest, and there were significant differences between each 2 groups (P＜0.05), without differences between the low and high dose groups (P＞0.05). The shortening score (FS) and ejection fraction (EF) were compared between each 2 groups, and the results showed that the indexes of the sham group were the highest, the BMSCs+b FGF group was slightly lower, the BMSCs group was much lower, the model group was the lowest, and there were significant differences between each 2 groups (P＜0.05). The levels of serum IL-10, the relative expressions of b FGF, TIMP-1 m RNA and protein were compared between each 2 groups, and the results showed that the indexes of the BMSCs+b FGF group were the highest, the BMSCs group was slightly lower, the model group was much lower, the sham group was the lowest, and there were significant differences between each 2 groups (P＜0.05). Conclusion BMSCs transfected with b FGF plasmid can significantly improve cardiac function and alleviate inflammatory response in rats after reperfusion, and can significantly reduce cardiomyocyte apoptosis, which may be related to the up-regulation of b FGF and the regulation of the paracrine mechanism of MMP-9/TIMP-1.
Keywords：Basic fibroblast growth factorBone marrow mesenchymal stem cellsAcute myocardial infarctionReperfusion injury
Publication Date：2019-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 674-679 )