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目的探讨T-同源盒转录因子5(TBX-5)在母鼠妊娠糖尿病(GDM)胎鼠心脏中的分布、表达规律及其在胎鼠心脏发育异常中的作用。方法将成年SD雌鼠随机分成GDM组和对照组,通过阴道涂片确定怀孕后分别注射链脲佐菌素(STZ)及柠檬酸-柠檬酸钠缓冲液(PBS)制备GDM模型,于孕0、3、6、9、12、15、19天对母鼠进行尾静脉采血测血糖,并分别于孕后第12、15、19天进行胎鼠心脏取材,HE染色观察心脏组织病理变化,免疫组化检测TBX-5的表达并进行半定量检测。结果与对照组相比,GDM组胎鼠出现液化吸收胎、死胎、畸心胎的例数增多(P<0.01)。在大体观及高倍镜下,GDM组12、15、19天胎鼠心脏发育异常比例多于对照组(P<0.01)。在正常对照组及GDM组各亚组中,TBX-5均在第12天时表达最强,明显高于15、19天(P<0.01)。TBX-5在15天及19天时的表达无明显差别(P>0.05)。孕12、15、19天GDM组TBX-5在心肌细胞表达显著增强,与相应时间点的对照组相比均明显增高(P<0.01)。结论 TBX-5蛋白在妊娠糖尿病母鼠孕12、15、19天三个观察点胎鼠心脏的表达水平明显增高,提示其过度表达可能与妊娠期糖尿病致胎鼠心脏畸形的发生存在关联。
Objective To investigate the distribution and expression of T-homeobox transcription factor 5 (TBX-5) in the heart of fetal rat with gestational diabetes mellitus (GDM) and its role in the development of fetal heart failure. Methods Adult female SD rats were randomly divided into GDM group and control group. GDM model was established by injecting streptozotocin (STZ) and citric acid-sodium citrate buffer solution (PBS) after vaginal smear. , 3, 6, 9, 12, 15 and 19 days respectively. The blood samples were collected from the tail vein to measure the blood glucose. The fetus hearts were harvested on day 12, day 15 and day 19 respectively. The pathological changes of heart tissue were observed by HE staining. The expression of TBX-5 was detected by histochemistry and semi-quantitatively detected. Results Compared with the control group, there were more cases of liquefied absorbed fetus, stillbirth and abnormal heartbirth in GDM group (P <0.01). In the general view and high magnification, GDM group 12, 15, 19 days fetal rat heart abnormalities than the control group (P <0.01). In the normal control group and GDM group, TBX-5 was the strongest on day 12, significantly higher than that on day 15 and day 19 (P <0.01). There was no significant difference in the expression of TBX-5 between day 15 and day 19 (P> 0.05). The expression of TBX-5 in GDM group was significantly increased at 12, 15 and 19 days of gestation, which was significantly higher than that of the control group at the corresponding time point (P <0.01). Conclusion The expression of TBX-5 protein in fetal rat hearts at gestational day 12, day 15 and day 19 was significantly higher than that of the normal control group, suggesting that overexpression of TBX-5 may be associated with the occurrence of fetal cardiac malformations in gestational diabetes mellitus.