GATA4基因H435Y位点突变对小鼠心功能的影响  

Effect of GATA4 Gene H435Y Mutation on the Heart Function of Mice

作　　者：方涛 陈名武 张慧 张甜 张晓光 朱昂昂 FANG Tao;CHEN Ming-wu;ZHANG Hui;ZHANG Tian;ZHANG Xiao-guang;ZHU Ang-ang(Provincial Hospital Affiliated to Anhui Medical University,Hefei,Anhui,230001,China)

机构地区：[1]安徽医科大学附属省立医院,安徽合肥230001

出　　处：《现代生物医学进展》2019年第5期846-850,共5页Progress in Modern Biomedicine

基　　金：安徽省自然科学基金项目(1608085MH196)

摘　　要：目的:研究GATA4基因H435Y位点突变对小鼠心功能的影响以及可能机制。方法:随机选取野生型(WT)小鼠和GATA4基因H435Y位点突变(Gata4 H435Y)小鼠各6只,检测和比较两组小鼠的心功能和心脏重量/体重比,应用Masson染色观察小鼠心肌组织形态,实时定量反转录聚合酶链式反应(qRT-PCR)和蛋白免疫印迹(Western blot)分别检测心肌组织中Gata4、Sox9、Scleraxis、Tenascin和Aggrecan的m RNA和蛋白表达水平。结果:与WT组小鼠相比,GATA4 H435Y组小鼠左心室射血分数(LVEF)和左心室缩短分数(LVFS)降低(P<0.05),左心室收缩末期内径(LVIDs)增大(P<0.05)。两组组小鼠的心脏重量比较差异无统计学意义(P>0.05),GATA4 H435Y组小鼠体重较WT组小鼠显著减轻、心重/体重比明显减小(P<0.05)。Masson染色结果显示两组小鼠心肌纤维无明显差异,但WT组小鼠心肌胶原纤维染色较深。与WT组小鼠相比较,GATA4 H435Y组小鼠心肌组织中GATA4、Scleraxis和Sox9的m RNA及蛋白明显表达下降(P<0.05),Aggrecan和TenascinmRNA和蛋白表达均无明显统计学差异(p>0.05)。结论:GATA4基因H435Y位点突变可能通过降低GATA4及下游基因表达,影响心肌细胞外基质基因的表达,进而损害小鼠的心功能。Objective:To study the effect of GATA4 gene H435Y mutation on the heart function of mice and its possible mechanisms.Methods:Our research included in 2 groups:Wild type(WT)mice group and Gata4 H435Y mutant(Gata4 H435Y)mice group,6 mice in each group.The heart function and the ratio of heart weight to body weight(HW/BW)were compared between 2 groups;the myocardial morphology was observed by Masson staining;the m RNA and protein expressions of GATA4,Sox9,Scleraxis,Tenascin and Aggrecan were determined by RT-PCR and Western blot analysis.Results:Compared with the WT mice,GATA4 H435Y mice group showed decreased LVEF,LV fraction shortening and increased left ventricular internal diameter at end-systole(LVESD)(P<0.05).The BW and ratio of HW/BW of GATA4 H435Y mice were obviously lower(P<0.05),the heart weight showed no significant difference between 2 groups(P>0.05).Masson staining showed that there was no significant difference in the myocardial fibers between the two groups,but the collagen fibers of myocardium in WT group were deeper.The m RNA and protein expressions of GATA4,Sox9 and Scleraxis were decreased in GATA4 H435Y mice(P<0.05),Tenascin and Aggrecan showed no significant difference between 2 groups(P>0.05).Conclusion:GATA4 gene H435Y mutation may affect the expression of extracellular matrix genes in cardiac muscle by reducing the expression of GATA4 and downstream genes,thereby impairing the cardiac function of mice.

关 键 词：GATA4 突变 心功能 细胞外基质 

分 类 号：R-33[医药卫生] Q132.7[生物学—普通生物学]