Nkx2.5在妊娠期糖尿病胎鼠心脏发育中的表达及意义

Expression and significance of Nkx2.5 in fetal murine heart development during gestational diabetes

目的:了解心肌转录因子Nkx2.5在妊娠期糖尿病(gestational diabetes mellitus,GDM)胎鼠心肌组织的表达变化,探讨其在妊娠期糖尿病胚胎心脏发育异常中可能的作用机制。方法:80只成年雌性SD大鼠,随机分为实验组(GDM组)和对照组各40只,实验组通过腹腔注射链脲佐菌素(streptozotocin,STZ)成功建立妊娠期糖尿病大鼠模型后,两组分别于孕12、15、19d随机分组并行剖腹产,取胎鼠心肌组织。采用免疫组织化学及实时荧光定量PCR检测Nkx2.5蛋白及mRNA在胎鼠心肌组织的表达。结果:对照组与实验组Nkx2.5蛋白及mRNA在胎鼠心肌组织的表达随胎龄的增长而呈上升趋势,同一时间点实验组Nkx2.5蛋白表达较对照组明显减少,差异有统计学意义(P<0.01);孕12及19 d实验组Nkx2.5mRNA表达较对照组明显减少,差异有统计学意义(P<0.01),孕15 d两组间无明显差异。结论:Nkx2.5蛋白及mRNA在妊娠期糖尿病胎鼠心肌组织的表达下降,可能参与了妊娠期糖尿病致胚胎先天性心脏病的发病过程。

Objective： To investigate the expression of cardiac-specific transcription factor Nkx2. 5 in fetal murine heart during pregnancy of mice with gestational diabetes,and explore its role in abnormal cardiac development in fetus from pregnant mice with diabetes. Methods： Eighty adult female SD mice were randomly divided into the study group（ GDM group）（ n = 40） and control group（ n = 40）. The model of pregnant mice with gestational diabetes was successfully established by intra-abdominal injection of streptozotocin（ STZ）. The cesarean section was randomly performed in the mice of the two groups on the 12 th,15th and 19 th days of pregnancy,respectively. The fetal mouse heart was obtained,and the expressions of Nkx2.5 protein and mRNA in fetal myocardium were detected by immunohistochemistry and real-time fluorescence-based quantitative PCR,respectively.Results： The expressions of Nkx2. 5 protein and mRNA in fetal myocardium were increased by gestational age in the two groups,and the expression of Nkx2.5 protein in study group was significantly lower than that in the control group at the same time point（ P〈0.01）; the expressions of Nkx2.5 mRNA in study group were significantly lower than those in the control group on the 12 th and 19 th days of pregnancy（ P〈0.01）,but there was no significant difference between two groups on the 15 th day of pregnancy. Conclusion： The down-regulated expressions of Nkx2.5 protein and mRNA in fetal myocardium may be involved in the pathogenesis of congenital fetal heart disease induced by gestational diabetes.