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目的 探讨高血糖、农药敌枯双的胎鼠致畸机理及牛磺酸的拮抗作用。方法 采用皮下注射高渗葡萄糖的方法致孕鼠高血糖 (高血糖组 )、给孕鼠饮用敌枯双 (敌枯双组 )、给孕鼠饮用牛磺酸 (牛磺酸拮抗组 )及其各自对照组 ,RT PCR及免疫组化方法检测各组胚胎组织中Pax3及Cx43基因的mRNA及其蛋白的表达。结果 高血糖组孕鼠血糖为 (13 4± 0 8)mmol/L ,吸收胎发生率为9 6%、死胎发生率为 4 3 %及神经管缺陷畸形发生率为 8 6% ,Pax3mRNA表达降低 (0 97± 0 2 0 ) ,Pax3蛋白也降低 (0 11± 0 0 2 ) ,Cx43mRNA过度表达 (7 0 5± 1 63 ) ,Cx43蛋白表达升高 (0 94±0 0 5) ;敌枯双组孕鼠Pax3mRNA的表达与高血糖组比较 ,无明显改变。但Cx43有过度表达 (Cx43mRNA 6 96± 0 73 ,Cx43蛋白 0 92± 0 12 ) ,与高血糖组比较 ,差异有极显著性 (P <0 0 1) ;牛磺酸组孕鼠的死胎、神经管缺陷畸形发生率均为 0 % ,吸收胎发生率为 2 8% ,Pax3及Cx43mRNA和蛋白均无过度表达现象。结论 (1)高血糖可能是糖尿病致畸的主要原因 ,其致畸机理可能是诱发Pax3基因突变 ,继而使Cx43基因过度表达 ;(2 )敌枯双的致畸作用可能是通过诱导Cx43基因过度表达而造成的 ;(3 )牛磺酸可通过改善Pax3及Cx43基因的表达而拮抗高血糖及敌枯
Objective To investigate the mechanism of teratogenicity and antagonism of taurine in fetus with hyperglycemia and pesticides. Methods Hypoglycemia was induced by hypodermic injection of glucose into the hyperglycemic mice. The pregnant rats were drenched with dizocarb (dizocarb group) and taurine (taurine antagonist group) The mRNA and protein expression of Pax3 and Cx43 in embryos of each group were detected by RT-PCR and immunohistochemistry. Results The blood glucose in the hyperglycemia group was (13 4 ± 0 8) mmol / L, the incidence of fetal absorption was 96%, the incidence of stillbirth was 43% and the incidence of neural tube defects was 8.6%, Pax3 mRNA was decreased (0 97 ± 0 2 0), Pax3 protein (0 11 ± 0 0 2), Cx43 mRNA overexpression (70 05 ± 1 63) and Cx43 protein expression (0 94 ± 0 0 5) Pax3 mRNA expression in the two groups of pregnant rats compared with the hyperglycemia group, no significant change. However, Cx43 was overexpressed (Cx43 mRNA 6 96 ± 0 73, Cx43 protein 0 92 ± 0 12), which was significantly different from the hyperglycemia group (P <0.01); stillbirth, The incidences of neural tube defects and deformities were 0% and 28%, respectively. There was no overexpression of Pax3 and Cx43 mRNA and protein. Conclusions (1) Hyperglycemia may be the main cause of diabetes teratogenicity. The teratogenic mechanism may be induced Pax3 gene mutation, which in turn leads to overexpression of Cx43 gene. (2) The teratogenic effect of prednisolone may be caused by the induction of excessive Cx43 gene (3) Taurine can antagonize the hyperglycemia and cytopathic effect by improving the expression of Pax3 and Cx43 genes