骨髓干细胞动员治疗急性心肌梗死大鼠的研究

目的研究粒细胞集落刺激因子(G-CSF)、辛伐他汀及二者联合治疗对急性心肌梗死(AMI)大鼠心肌细胞损伤和凋亡的影响和机制。方法建立SD大鼠AMI模型,术后24 h存活者随机分为心梗组(MI)、G-CSF组(MI-G)、辛伐他汀组(MI-S)、G-CSF联合辛伐他汀组(MI-GS),另设假手术组(SO);上述各组又再随机分为2 d、14 d、28 d三个不同时间亚组,用免疫组化染色检测外周血CD34细胞、血管内皮生长因子(VEGF)、原位末端标记法(TUNEL)评估调亡细胞。结果①外周血CD34阳性细胞百分比:MI组高于SO组(P<0.05),而各治疗组均高于MI组(P<0.01);②大鼠心肌梗死区VEGF的积分光密度值:MI组高于SO组(P<0.01),而治疗组高于MI组(P<0.01)。③细胞凋亡指数:治疗组低于MI组(P<0.01),但高于SO组(P<0.01),而MI-GS组低于MI-G、MI-S组(P<0.05)。结论骨髓干细胞动员剂G-CSF、辛伐他汀不仅能诱导干细胞的动员,而且降低炎症反应、促进再生心肌血管及抑制心肌细胞凋亡的作用,两者合用效果更佳。上述结果为骨髓干细胞动员剂临床应用治疗心肌梗死提供了实验依据。

Experimental study of the treatment of the mobilization of bone marrow stem cells in acute myocardial infarction rats

Objective To investigate the effects and mechanism of G - CSF, simvastatin and their combination on the damage and apoptosis of myocardial cells in acute myocardial infarction （AMI） rats. Methods The AMI model was established in SD rats. Twenty - four hours after the ligation of the left anterior descending coronary artery, surviving rats were randomly divided into five groups.. MI group, G - CSF group, simvastatin （MI -S） group, G- CSF and simvastatin （MI -GS） group, and sham- operated （SO） group. Then rats in each group were further assigned to three subgroups according to the days （2 d, 14 d and 28 d, respectively） of experiment. Immunohistoehemistry staining was performed to lable CD34 and VEGF. The apoptotic myocardial cells were quantified by TUNEL staining. Results 1. The percentage of CD34 positive cells of peripheral blood was higher significantly in MI group comparing with that in SO group （ P 〈0. 05 ）, and it was higher in treatment group than that in MI group （ P 〈0.01 ）. 2. The level of integrated optical density of VEGF was higher significantly in MI group comparing with SO group （ P 〈0.01 ） , and it was higher significantly in treatment group comparing with that in MI group （ P 〈0.01 ）. 3 The apoptosis index was decreased significantly in treatment group comparing with that in MI group （ P 〈0.01 ）, but it was higher comparing with that in SO group （ P 〈0.01 ） ; and the apoptosis index was decreased in MI - GS group comparing with those in MI - G and MI - S groups （ P 〈 0.05 ）. Conclusion G - CSF and simvastatin not only promote stem cells mobilizing, but also significantly depress inflammation, and attenuate the apoptosis of myocardial cells ; and these effects are reinforced by the combined use of G - CSF and simvastatin.