Role of apoptosis and the expression of bax and bcl-2 on diabetic embryopathy

母亲怀孕期间的糖尿病与后代畸形和生长障碍的发生率增加有关。程序性细胞死亡通常是最常见的细胞死亡方式，存在于形态发生的许多发育过程中。为探讨细胞凋亡及促进和抑制细胞凋亡的bax和bcl2在糖尿病胚胎畸形中的作用，采用末端脱氧核苷酸转移酶介导的缺口末端标记法和免疫组织化学技术，检测了正常和糖尿病小鼠妊娠9、10、11d胚胎的细胞凋亡和Bax、bcl2的表达。我们发现：在正常大鼠胚胎中，从第9天到第11天，在原始肠道中总是检测到凋亡细胞，并伴随着Bax的强表达，bcl2在没有凋亡细胞的区域表达。在神经管和体节中，第10天和第11天，神经管和体节内可见凋亡细胞，并伴有bax的表达，bcl2表达较弱。在原始心脏中，第10天和第11天，很少检测到凋亡细胞，Bax和bcl2在该区域有较强的表达。在STZ大鼠胚胎中，第10天和第11天，原始肠道、神经管、体节和咽部的凋亡细胞增加。Bax在该区域呈强阳性表达，bcl2呈弱阳性表达。结论：在糖尿病状态下，促凋亡基因Bax的表达增加，导致程序性细胞死亡的异常率，导致分化和迁移细胞的丧失，在糖尿病妊娠的先天性畸形中起着至关重要的作用。

Maternal diabetes during pregnancy is associated with increased rate of malformations and growth disturbances in the offspring. Programmed cell death is normally the most common mode of cell death and is present in many developmental processes during morphogenesis. To investigate the role of apoptosis and expression of bax and bcl-2 which promote and inhibit apoptosis on diabetic embryonic malformation, embryos from normal and diabetic mice on day 9,10, and 11 of gestation were examined by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and immunohistochemical technique. We found: in embryos from normal rats, in primitive gut apoptotic cells were always detected through day 9 to 11, accompanying with strong expression of bax, bcl-2 was expressed in the region where no apoptotic cells. In neural tube and somite, one day 10 and 11, apoptotic cells were detected accompanying with expression of bax in the region; bcl-2 was weakly expressed. In primitive heart, on day 10 and 11, apoptotic cells were rarely detected, and there was strong expression of bax and bcl-2 in the region. In embryos from STZ rats, on day 10 and 11, increased apoptotic cells were detected in primitive gut, neural tube, somite and pharyngealarch. Strong expression of bax and low expression of bcl-2 was observed in the region. In conclusion in diabetic condition increased expression of bax-apoptosis promoting gene-induced abnormal rates of programmed cell death, leading to the loss of the differentiating and migrating cells and has crucial role in congenital malformation in diabetic pregnancy.