AIM:To study the effect of Hand2 (one of basic helix-loop-helix proteins’ transcription factors) expression on the development of the cardiac tissues in the fetal rats from gestational diabetes mellitus ( GDM) parents, and to investigate the potential pathogenesis of GDM-induced congenital cardiac defects in rats.METHODS: The adult Spra-gue-Dawley female rats were randomly divided into blank control group (n=24), GDM group (n=30), negative control group ( n=30) and insulin intervened group ( n=30) .The GDM model was established by intraperitoneal injection of 2%streptozotocin (STZ, 40 mg/kg body weight) to the pregnant rats on the successive day.The rats in insulin intervened group were injected with intermediate-acting insulin in order to keep the fasting blood glucose in the normal range.The rats in negative control group were injected with citric acid-sodium citrate buffer solution in the same position.Blood glucose and body weight were examined every day 72 h after STZ injection.On E12, E15 and E19, the rats were anesthetized and the embryonic cardiac tissues were collected after caesarean section.The histopathological changes of the cardiac tissues were observed under microscope with HE staining.The expression of Hand2 was analyzed by the method of immunohisto-chemistry.The expression of Hand2 in the cardiac tissues at mRNA and protein levels was determined by real-time fluores-cence quantitative PCR and Western blotting.RESULTS:During the development of embryonic heart, the protein expres-sion of Hand2 in the cardiac tissues was showed dynamic changes.Observed on E12, obviously increased on E15, and at the highest level on E19.Compared with the other 3 groups, the protein and mRNA expression of Hand2 in GDM group was decreased at the time points of E12 and E15.CONCLUSION:The morbidity of fetal cardiac malformation is significantly increased in GDM group, suggesting that Hand2 may be involved in the development of cardiac malformation in GDM.%目的：了解妊娠糖尿病（ gestational diabetes mellitus，GDM）母鼠胎鼠心脏发育过程中碱性螺旋-环-螺旋蛋白（ basic helix-loop-helix，bHLH）转录因子Hand2表达的变化规律，探讨其在GDM胎鼠心脏发育异常中的作用机制。方法：114只成年雌性SD大鼠，空白对照组（ n＝24）、GDM组（ n＝30）、阴性对照组（ n＝30）及GDM＋胰岛素干预组（ n＝30）；空白对照组不予任何处理；GDM组腹腔注射2％链脲佐菌素（ streptozotocin，STZ；每只40 mg /kg）；阴性对照组腹腔注射等量的柠檬酸－柠檬酸钠缓冲液（ STZ溶剂）；GDM＋胰岛素干预组在GDM建模成功后皮下注射中效胰岛素控制空腹血糖在正常范围。给药72 h后每天测血糖及体质量，各组分别于孕12 d （ embryotic day 12， E12）、E15和E19剖取胎鼠心脏组织HE染色观察心脏组织病理变化，免疫组化检测Hand2蛋白的表达，实时荧光定量PCR检测Hand2 mRNA的表达，Western blotting检测Hand2蛋白表达的变化。结果：各组Hand2蛋白的表达呈动态变化：E12可见表达，E15时表达增加，E19时Hand2蛋白表达最高，E12和E15 GDM组Hand2 mRNA及蛋白在胎鼠心肌细胞中的表达呈现下降趋势，差异有统计学意义（ P＜0．05）。结论：妊娠糖尿病母鼠其胎鼠心脏发育异常的发生率明显升高；Hand2 mRNA及蛋白在妊娠糖尿病胎鼠E12和E15心脏表达水平明显下降，提示与GDM胎鼠心脏发育异常相关。
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