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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 transcription factor Nkx2.5 in fetal cardiac muscle of gestational diabetes mellitus (GDM), and to explore its possible mechanism in cardiac dysplasia of gestational diabetes mellitus (GDM). Methods: Eighty adult female Sprague-Dawley rats were randomly divided into experimental group (GDM group) and control group (n = 40). The experimental group was successfully established by intraperitoneal injection of streptozotocin (STZ) , Respectively. The two groups were randomized to caesarean section at 12, 15 and 19 days of gestation respectively, and the myocardial tissue of fetus was taken. The expression of Nkx2.5 protein and mRNA in fetal rat myocardium was detected by immunohistochemistry and real-time fluorescence quantitative PCR. Results: The expression of Nkx2.5 protein and mRNA in fetal rat hearts increased with gestational age in the control group and experimental group. The expression of Nkx2.5 protein in the experimental group was significantly lower than that in the control group at the same time point (P <0.01). Compared with the control group, the expression of Nkx2.5 mRNA in the experimental group on the 12th and 19th day of pregnancy was significantly decreased (P <0.01). There was no significant difference between the two groups on the 15th day of pregnancy. Conclusion: The decreased expression of Nkx2.5 protein and mRNA in fetal rat cardiac myocytes during gestational diabetes mellitus may be involved in the pathogenesis of congenital heart disease induced by gestational diabetes mellitus.