GATA-4在妊娠期糖尿病胎鼠心脏中的表达

摘要

AIM: To study the expression of transcription factor GATA binding protein 4 ( GATA-4 ) in the development of the cardiac tissues in the fetal mice from gestational diabetes mellitus (GDM) mice, and to investigate the potential pathogenesis of GDM-induced congenital cardiac defects in mice. METHODS: The adult Sprague-Dawley female mice were randomly divided into control group ( n = 40) and GDM group ( n = 40). The GDM model was established by in-traperitoneal injection of 2% streptozotocin (STZ, 40 mg/kg body weight in 0. 1 mol/L sodium citrate, pH 4. 4) to the pregnant mice on the successive days. The mice in control group were injected with citric acid-sodium citrate buffer solution in the same position. Blood glucose and body weight were examined every day after STZ injection for 72 h. On E12, E15 and E19, the mice were anaesthetized and the embryonic cardiac tissues were collected after caesarean section. The his-topathological changes of the cardiac tissues were observed under microscope with HE staining. The expression of GATA-4 was analyzed by the method of immunohistochemistry. The expression of GATA-4 in cardiac tissues at mRNA and protein levels was determined by real-time fluorescence quantitative RT-PCR and Western blotting. RESULTS: During the development of embryonic heart, the expression of GATA-4 protein in the cardiac tissue was observed on E12, and it was obviously increased on E15, but it was decreasd on E19. Compared with control group, the expression of GATA-4 protein in GDM group was decreased at the time points of E12, E15 and E19. The mRNA expression of GATA-4 in GDM group was lower than that in control group at the same time points. Compared with control group, the protein level of GATA-4 in GDM group was diminished. CONCLUSION: The morbidity of fetal cardiac malformation is significantly increased in GDM group, suggesting that GATA-4 may be involve in the development of cardiac malformation in GDM.%目的:了解妊娠期糖尿病(gestational diabetes mellitus,GDM)胎鼠心脏发育过程中锌指转录因子GATA结合蛋白4(GATA binding protein 4,GATA-4)的变化规律,为深入探讨其在GDM胎鼠心脏发育异常中的作用机制奠定基础.方法:80只SPF级成年SD雌鼠随机分为对照组(n=40)和GDM组(n=40),通过阴道涂片确定受孕后,GDM组予腹腔注射2％链脲佐菌素(streptozotocin,STZ;每只40 mg/kg),对照组予腹腔注射等量的柠檬酸-柠檬酸钠缓冲液.给药72 h后每天监测血糖,各组分别于孕12、15、19 d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GATA-4的表达,实时荧光定量RT-PCR检测GATA-4 mRNA的表达,Western blotting检测GATA-4蛋白的变化.结果:对照组及GDM组GATA-4蛋白的表达呈动态变化:孕12 d可见表达,孕15 d表达最高,孕19 d表达下降；与对照组相比,GDM组GATA-4mRNA及蛋白的表达呈现下降趋势,差异有统计学意义(P＜0.05).结论:妊娠期糖尿病胎鼠心脏发育异常率显著增高,GATA-4与GDM胎鼠心脏发育异常可能有相关性.