摘要
目的探索黏着斑激酶(FAK)及其介导下游信号通路AKT/S6K在心房颤动(房颤)小鼠模型心房重构中分子改变。方法利用为心脏特异性表达人源肾素原受体(pRR)的转基因小鼠作为房颤小鼠模型,选取野生型C57BL/6J小鼠为对照组,两组各选取16例8月龄小鼠作为研究对象,通过超声心动图检测观察心房心室改变;获取心房组织,分别进行Masson病理染色和蛋白免疫印迹,观察两组纤维化程度和FAK及其下游通路在两组小鼠心房组织中的变化。结果房颤模型小鼠在8月龄已经岀现明显的持续性房颤,超声心动图提示房颤组小鼠心房和心室都较对照组小鼠扩大,有心房重构。病理提示房颤组小鼠心房纤维化程度较高,同时FAK及下游AKT/S6K通路蛋白的磷酸化表达均发生上调。结论心房重构是房颤引起的心肌组织结构的变化,为房颤持续和血栓形成提供基质。房颤可引起心房扩大和纤维化形成,其中FAK介导的AKT/SK通路可能是参与重构的重要分子。
Objective To explore the molecular changes of focal adhesion kinase(FAK)and its downstream signaling pathway AKT/S6K in atrial remodeling in mice with atrial fibrillation(AF).Methods Using transgenic mice expressing human renninogen recepto(pRR)specifically for the heart as the model of AF and wild C57BL/6J mice as the control group;168-month-old mice each group were selected as the research objects and the atrioventricular changes were observed by ultrasonography.Atrial tissues were obtained and Masson staining and protein immunoblotting were performed to observe the degree of fibrosis and the changes of FAK and its downstream pathway in the atrial tissues of the two groups.Results The persistent AF was observed in the AF model mice at the age of 8 months.Echocardiography showed that both the atria and ventricles of the AF group were enlarged compared with those of the control group.Masson staining showed that atrial fibrosis was higher in AF group and the phosphorylation of FAK and downstream AKT/S6K pathway protein were upregulated by western blotting.Conclusion Atrial remodeling is the change of myocardial tissue structure caused by atrial fibrillation,which provides a matrix for the persistence of AF and thrombosis.AF can cause atrial enlargement and fibrosis;FAK・mediated AKT/S6K pathway may be an important molecule involved in remodeling.
作者
张培德
李飞
芮璐
王巍
ZHANG Pei-de;LI Fei;RUI Lu;WANG Wei(Cardiac Surgery Department,Fuwai Hospital,China Academy of Medicine Science,National Center for Cardiovascular Disease,Peking Union Medical College,Beijing 100037,China)
出处
《中国心血管病研究》
CAS
2020年第1期37-41,共5页
Chinese Journal of Cardiovascular Research
基金
国家自然科学基金青年基金(816002541004453)。
关键词
房颤模型
心房重构
黏着斑激酶
信号通路
Atrial fibrillation model
Atrial remodeling
Focal adhesion kinase
Signaling pathway
