PDZ-LIM基因与人心肌肥厚相互关系初探  

Preliminary Study on the Relationship Between PDZ-LIM Gene and Human Myocardial Hypertrophy

作　　者：郭宏伟[1] 匡锋[1] 蒋媛媛[2] 赖轶权[1] 陈取 GUO Hongwei;KUANG Feng;JIANG Yuanyuan;LAI Yiquan;CHEN Qu(Department of Cardiovascular Surgery,The First Affiliated Hospital of Xiamen University,Xiamen,Fujian 361000,China;Department of Ultrasound Imaging,The First Affiliated Hospital of Xiamen University,Xiamen,Fujian 361000,China)

机构地区：[1]厦门大学附属第一医院心脏外科,福建厦门361000 [2]厦门大学附属第一医院超声影像科,福建厦门361000

出　　处：《中国医药指南》2025年第2期1-4,共4页Guide of China Medicine

基　　金：厦门市科技计划项目(3502Z20194008)。

摘　　要：目的探讨肥厚型心肌病(HCM)中Enigma家族蛋白的作用及其与心肌发育和功能异常的关联。方法通过复制缺陷腺病毒为载体,将携带PDZ-LIM结构域片段的点突变序列和正常序列转染至et-1诱导的大鼠心肌细胞中,分成实验组和对照组,采用心肌病模型建立、心肌细胞形态及Z线结构电镜观察、2D-gel电泳和质谱分析、免疫荧光染色以及统计分析等方法,以阐明PDZ-LIM基因与人心肌肥大的相互关系,并解释其分子生物学机制。结果实验组小鼠心肌细胞平均直径、面积高于对照组,且PDZ-LIM基因的蛋白表达高于对照组,差异有统计学意义(P<0.05)。通过免疫荧光染色和电镜观察,HCM小鼠心肌细胞Z线结构发生变化,介导心脏细胞整体结构变化和Z线内蛋白分布。超微结构透射电子显微镜分析显示,突变型心肌的Z线出现中断和紊乱,M线的形态相对正常。结论HCM心肌细胞PDZ-LIM基因表达增高,在一定程度上能反映出心肌细胞的病理变化,与肥厚型心肌病存在相关性。Objective This study aims to investigate the role of Enigma family proteins in Hypertrophic Cardiomyopathy(HCM)and their association with myocardial development and functional abnormalities.Methods The point mutation sequence and normal sequence carrying PDZ-LIM domain fragment were transfected into et1-induced rat cardiomyocytes by replicating defective adenovirus,and then divided into experimental group and control group.To elucidate the relationship between PDZ-LIM gene and human cardiac hypertrophy,and explain its molecular biological mechanism,cardiomyopathy model was established,cardiomyocyte morphology and Z-line structure were observed by electron microscopy,2D-gel electrophoresis and mass spectrometry,immunofluorescence staining and statistical analysis.Results The mean diameter and area of myocardial cells in the experimental group were higher than those in the control group,and the protein expression of PDZ-LIM gene was higher than that in the control group,with statistical significance(P<0.05).By immunofluorescence staining and electron microscope observation,the Z-line structure of HCM mouse cardiomyocytes was changed,which mediated the overall structure change of heart cells and the protein distribution in Z-line.In addition,ultrastructural transmission electron microscopy showed that the Z-line of the mutant myocardia was interrupted and disordered,while the M-line was relatively normal.Conclusions The abnormal expression of PDZ-LIM gene can reflect the pathological changes of cardiomyocytes to a certain extent,which is correlated with hypertrophic cardiomyopathy,and has important clinical diagnosis and treatment value.

关 键 词：肥厚型心肌病 PDZ-LIM基因 Enigma家族蛋白 磷酸化 

分 类 号：R542.2[医药卫生—心血管疾病]