大鼠肥厚心脏卸负荷后心室逆重塑相关的信号通路改变  

Signal pathways involved in reverse remodeling of the hypertrophic heart in rat after pressure unloading

作　　者：徐瑞霞[1] 郑哲[1] 林富强[2] 张士举[1] 陈曦[1] 胡盛寿[1] 

机构地区：[1]中国医学科学院阜外心血管病医院,卫生部心血管疾病再生医学重点实验室,北京100037 [2]温州医学院附属第一医院胸外科,浙江温州325000

出　　处：《中国病理生理杂志》2009年第4期625-630,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30872538)

摘　　要：目的:研究肥厚心脏心室重塑及逆重塑过程中Akt/GSK3β、MAPKs和NF-κB信号通路的变化。方法:以Lewis大鼠行腹主动脉缩窄术,建立压力超负荷性心肌肥厚模型。将肥厚心脏移植到同源Lewis大鼠腹部,建立压力卸负荷模型。对各组心肌取材进行病理学评价。Western blotting法检测心肌组织中相关信号通路蛋白的表达。结果:在心肌肥厚大鼠心脏中Akt/GSK3β、MAPKs和NF-κB磷酸化水平均显著升高,移植卸负荷后除p38 MAPK和JNK外,其它蛋白磷酸化水平均显著降低。结论:肥厚心脏经异位移植卸负荷后产生逆重塑现象,Akt/GSK3β、ERK1/2和NF-κB信号通路的改变参与其中,该结果为临床心室逆重塑的研究提供了实验依据。AIM： Heterotopic transplantation of rat hypertrophic hearts has been shown to reverse chamber enlargement and regress cardiac myocyte hypertrophy. The purpose of this study was to gain a better understanding of molecular changes associated with the beneficial reverse remodeling after pressure unloading of hypertrophic heart. METHODS： Stable cardiac hypertrophy was induced by abdondnal aortic constriction （AAC） in Lewis rats （6 weeks）. Left ventricular （LV） pressure unloading was induced by heterotopic transplantation of hypertrophic hearts （ AAC - HT） and/or normal hearts （NL- HT） （2 weeks）. We measured heart weight （HW） and LV weight （LVW） of all groups. Cross -sectional area of cardiomyocyte was assessed by hematoxylin/eosin staining. We further analyzed the regulation of prohypertrophic signaling pathways of mitogen -activated protein kinases （MAPKs）, Akt/GSK3βand NF-κB in both transplanted groups by Western blotting. RESULTS ： The HW and LVW in AAC hearts were higher （ P 〈 0. 05 ） than those in normal controls, but the transplanted hearts in AAC - HT group showed a significant reduction in HW and LVW compared to the AAC hearts. Pressure unloading induced a decrease in cardiomyocyte size in AAC - HT and NL - HT hearts. A significant decrease in phosphorylation of p44/p42 MAP kinases （ERK）, Akt, GSK3β and NF - KB was detected in AAC -HT hearts, but the phosphorylation of p38 MAP kinase and Jun -N -terminal kinase （JNK） were not changed compared to AAC hearts. The phosphorylation of MAPKs, Akt/GSK3β and NF-κB showed no difference between NL - HT hearts and normal controls. CONCLUSION ： Pressure unloading of the hypertrophic heart caused a reverse remodeling through regulating the ERK, Akt/GSK3β and NF-κB signal pathways which act as potential target pathways for reversal of LV hypertrophy.

关 键 词：心肌肥厚 异位心脏移植 逆重构 信号转导 

分 类 号：R363[医药卫生—病理学]