糖原合成酶激酶3β过表达心肌干细胞移植治疗心肌梗死

Overexpression of glycogen synthase kinase 3 beta in the treatment of myocardial infarction with cardiac stem cell transplantation

背景:糖原合成酶激酶3β(GSK-3β)与细胞的各项生命活动之间存在密切的联系,关于其在心肌干细胞向心肌细胞分化中的作用机制和效果尚不清楚。目的:探讨GSK-3β过表达心肌干细胞移植治疗心肌梗死大鼠的效果。方法:分离培养乳鼠心肌干细胞,使用慢病毒感染心肌干细胞使其过表达GSK-3β或对照基因LacZ。30只SD大鼠制备心肌梗死模型随机分为3组:GSK-3β组、LacZ组、PBS组。模型制备后6周,于梗死心肌内局部注射过表达GSK-3β、Lac Z心肌干细胞以及等量PBS。移植后4周,检测心功能及心室胶原生成情况。结果与结论:(1)GSK-3β组的左室射血分数显著大于其他两组(P<0.05),左室舒张末内径显著小于其他两组(P<0.05);(2)GSK-3β组羟脯氨酸含量、Ⅰ型胶原mR NA、Ⅲ型胶原m RNA表达显著小于其他两组(P<0.05);(3)经Masson染色发现,GSK-3β组的心室肌蓝染的胶原含量明显低于LacZ组;(4)GSK-3β组的心肌梗死范围显著小于其他两组(P<0.05);(5)实验结果表明,心肌干细胞过表达GSK-3β能提高心肌干细胞移植治疗效果。

BACKGROUND： The mechanism and effect of glycogen synthase kinase 3β（GSK-3β） in the differentiation of cardiac stem cells into cardiomyocytes are still unclear, although GSK-3β is closely related to the life activities of cells.OBJECTIVE： To investigate the changes of GSK-3β expression in the treatment of myocardial infarction in rats undergoing cardiac stem cell transplantation. METHODS： The isolation and culture of cardiac stem cells were performed in 10 neonatal rats. Lentivirus overexpressing GSK-3β or LacZ（control） was constructed and transferred into cardiac stem cells. Animal model of myocardial infarction was made in 30 Sprague-Dawley rats. Six weeks after model preparation, rat models were assigned into GSK-3β, Lac Z or PBS group. GSK-3β or LacZ overexpressing cardiac stem cell solution or PBS in equal volume was injected into the rat myocardium, respectively. Four weeks after transplantation, the cardiac function and myocardial collagen production in rats were detected and compared. RESULTS AND CONCLUSION： Compared with the other two groups, the left ventricular ejection fraction was significantly higher, and the left ventricular end diastolic diameter was significantly lower in the GSK-3β group（P〈0.05）. Hydroxyproline content, type I collagen m RNA, and type III collagen m RNA expression were significantly lower in the GSK-3β group than the other two groups（P〈0.05）. Findings from Masson staining showed that the content of blue-stained collagen was significantly lower in the GSK-3β group than the Lac Z group. Moreover, lowest myocardial infarction size was found in the GSK-3β group（P〈0.05）. All these experimental findings show that GSK-3 overexpression plays a positive role in promoting the therapeutic effect of cardiac stem cell transplantation.