GATA4基因H435Y位点突变对小鼠心功能的影响

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(P0.05),左心室收缩末期内径(LVIDs)增大(P0.05)。两组组小鼠的心脏重量比较差异无统计学意义(P0.05),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(P0.05)。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(P0.05),Aggrecan和TenascinmRNA和蛋白表达均无明显统计学差异(p0.05)。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。

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

ABSTRACT Objective: To study the effect of GATA4 gene H435Y mutation on the heart function of mice and its possible mecha- nisms. 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 my- ocardial morphology was observed by Masson staining; the mRNA 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 be- tween 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 mRNA and protein expressions of GATA4, Sox9 and Scle- raxis 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.