直接心肌内注射碱性成纤维细胞生长因子基因改善慢性缺血心肌收缩功能的实验研究

Experimental study on effects of direct intramyocardial injection of basic fibroblast growth factor gene on systolic function of chronic ischemic myocardiam

目的观察直接心肌内注射碱性成纤维细胞生长因子(bFGF)基因对慢性缺血心肌收缩功能的改善作用。方法将10只猪的慢性心肌缺血模型,随机分为bFGF基因治疗组(A组,6只)和对照组(B组,4只)。超声心动图(UCG)和MRI检测左心室射血分数(LVEF)和室壁增厚率(WT),评价左心室收缩功能。治疗后6周,目标区心肌标本进行心肌微血管计数。结果bFGF基因治疗后6周,UCG测得A组LVEF和WT均较治疗前提高(P<0.05),WT提高到正常值水平;A组WT值高于B组(P<0.05)。MRI测得A组LVEF和WT均较治疗前提高(P<0.05),并且达到正常值水平;A组LVEF和WT均高于B组(P<0.05)。A组心肌微血管计数多于B组(P=0.031)。结论直接心肌内注射bFGF基因可以促进心肌细小血管新生,改善慢性缺血心肌局部和左心室整体的收缩功能。

Objective To evaluate the effect of intramyocardial injection of the basic fibroblast growth factor （bFGF） gene on left ventricular systolic function in porcine model of chronic myocardial ischemia. Methods Ten chronic myocardial ischemic porcine models were divided into two groups, group A（ bFGF gene treatment group, n =6） and group B （control group, n =4）. UCG and MRI were used and left ventricular ejection fraction （LVEF） and systolic wall thickening （WT） were examined to assess the left ventricular systolic func- tion. Six weeks after the treatment, the target myocardial tissue sections were stained with hematoxylin/eosin （HE） and the capillary density was calculated. Results UCG results showed that six weeks after bFGF gene therapy, LVEF and WT in group A were significantly improved as compared with those before treatment （ P 〈 0.05）, WT was increased to the normal level and was significantly higher than that in group B （ P = 0.004）. MRI results indicated that in group A, both LVEF and WT were increased to normal levels six weeks after bFGF gene treatment and were significantly higher than those before treatment （ P 〈 0.05）. While in group B, neither LVEF nor WT was significantly changed as compared with those before treatment and both were significantly lower than the normal levels （ P = 0. 000）. At the study endpoint, LVEF and WT in group A were significantly higher than those in group B （ P =0.000）. The capillary density in group A was significantly higher than that in group B （ P = 0. 031）. Conclusions Direct intramyocardial injection of bFGF gene can significantly enhance angiogensis and collateral circulation, which contribute to the significant improvement of regional or global left ventricular systolic function in chronic myocardial ischemia of porcine heart.