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CyPA-CD147-ERK1/2-cyclin D2信号通路在大鼠左心室肥厚过程中表达上调

唐福才, 王红艳, 马明明, 关天旺, 潘龙, 姚敦琛, 陈亚兰, 陈玮贝, 涂永生, 付晓东

广州医科大学1基础学院生理学教研室；第一临床学院；基础学院病理学教研室；第二临床学院；第三临床学院，广州 510182；中山大学中山医学院药理学教研室，广州 510089

摘要

亲环素A (cyclophilin A, CyPA)，其受体CD147及其下游信号通路在心肌肥厚过程中变化情况不清楚。本实验目的是研究血清CyPA、心肌中CyPA、 CD147及其信号通路与心肌肥厚的关系。大鼠左心室肥厚模型用2肾2夹(2-kidney, 2-clip, 2K2C)方法制备，并观察1周，4周和8周。用左心质量和体重比值(ratio of left ventricular heart weight to body weight, LVW/BW)及心肌横切面面积(cross sectional area, CSA)评价左心室肥厚。用ELISA检测血清中CyPA水平。用蛋白免疫印迹和免疫组化观察CyPA、CD147、磷酸化ERK1/2和cyclin D2在心肌组织中表达水平。在第4周和8周，与对照组比较，2K2C组大鼠血压明显增高，LVW/BW和CSA显著增加。ELISA结果显示2K2C组大鼠血清中CyPA水平随着左心室肥厚程度加剧而明显增加。蛋白免疫印迹和免疫组化结果表明，CyPA、CD147、磷酸化ERK1/2和cyclin D2在2K2C组大鼠心肌组织中表达水平也随左心室肥厚发展而增加。本研究表明血清中CyPA水平以及心肌组织中CyPA-CD147-ERK1/2-cyclin D2信号通路在心肌肥厚发展过程中被激活并表达上调，提示该信号通路在左心室肥厚发病机制中可能发挥了作用。

关键词： CD147; 亲环素A; 心肌肥厚; 高血压

分类号：R363

CyPA-CD147-ERK1/2-cyclin D2 signaling pathway is upregulated during rat left ventricular hypertrophy

TANG Fu-Cai, WANG Hong-Yan, MA Ming-Ming, GUAN Tian-Wang, PAN Long, YAO Dun-Chen, CHEN Ya-Lan, CHEN Wei-Bei, TU Yong-Sheng, FU Xiao-Dong

Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079；Department of Physiology, School of Basic Sciences； The First Clinical Medical College； Department of Pathology, School of Basic Sciences； The Second Clinical Medical College； The Third Clinical Medical College, Guangzhou Medical University, Guangzhou 510182, China； Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510089, China

Abstract

The changes of serum cyclophilin A (CyPA), its receptor CD147 and the downstream signaling pathway during the process of cardiac hypertrophy remain unknown. The present study aims to investigate the relationships between CyPA-CD147-ERK1/2-cyclin D2 signaling pathway and the development of cardiac hypertrophy. Left ventricular hypertrophy was prepared by 2-kidney, 2-clip in Sprague-Dawley rats and observed for 1 week, 4 and 8 weeks. Left ventricular hypertrophy was evaluated by ratio of left ventricular heart weight to body weight (LVW/BW) and cardiomyocyte cross sectional area (CSA). CyPA levels in serum were determined with a rat CyPA ELISA kit. Expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular myocytes were determined by Western blot and immunostaining. Compared with sham groups, systolic blood pressure reached hypertensive levels at 4 weeks in 2K2C groups. LVW/BW and CSA in 2K2C groups were significantly increased at 4 and 8 weeks after clipping. ELISA results indicated a prominent increase in serum CyPA level associated with the degree of left ventricular hypertrophy. Western blot revealed that the expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular tissues were also remarkably increased as the cardiac hypertrophy developed. The results of the present study demonstrates that serum CyPA and CyPA-CD147-ERK1/2-cyclin D2 signaling pathway in ventricular tissues are time-dependently upregulated and activated with the process of left ventricular hypertrophy. These data suggest that CyPA-CD147 signaling cascade might play a role in the pathogenesis of left ventricular hypertrophy, and CyPA might be a prognosticator of the degree of left ventricular hypertrophy.

Key words: CD147; cyclophilin A; cardiac hypertrophy; hypertension

收稿日期：2015-03-09　　录用日期：2015-05-27

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引用本文：

唐福才, 王红艳, 马明明, 关天旺, 潘龙, 姚敦琛, 陈亚兰, 陈玮贝, 涂永生, 付晓东. CyPA-CD147-ERK1/2-cyclin D2信号通路在大鼠左心室肥厚过程中表达上调[J]. 生理学报 2015; 67 (4): 393-400.

TANG Fu-Cai, WANG Hong-Yan, MA Ming-Ming, GUAN Tian-Wang, PAN Long, YAO Dun-Chen, CHEN Ya-Lan, CHEN Wei-Bei, TU Yong-Sheng, FU Xiao-Dong. CyPA-CD147-ERK1/2-cyclin D2 signaling pathway is upregulated during rat left ventricular hypertrophy. Acta Physiol Sin 2015; 67 (4): 393-400 (in Chinese with English abstract).