妊娠期暴露氯氮平对胎儿营养物质转运的影响及机制

Effects of exposure to clozapine during pregnancy on fetal nutrient transport and its mechanism

目的:探讨妊娠期暴露氯氮平对胎儿营养物质转运的影响及其机制的研究。方法:选取2018年6月~2020年6月潮州市第三人民医院精神科收治的26例妊娠期暴露氯氮平的患者为研究对象,另择同期正常足月自然或剖宫产分娩孕妇26例纳入对照组。对比两组对象的血清学指标水平;采用酶联免疫吸附试验(ELISA)检测胎盘组织滋养层细胞中各类营养物质的水平;实时定量RT-PCR测定各转运载体蛋白基因的相对表达水平并对比。结果:观察组对象母体血清中血清学指标白蛋白、葡萄糖、碱性磷酸酶显著低于正常组(P<0.05),血氨水平显著高于正常组(P<0.05);观察组中苏氨酸、缬氨酸、异亮氨酸、组氨酸、天冬酰胺及甘氨酸均低于正常组水平,且数据差异具有统计学意义(P<0.05);观察组的胎盘组织中氨基酸转运载体中性氨基酸转运载体1、2(SNAT1、2)、谷氨酸转运载体3(EAAT3)、L型氨基酸转运载体2(LAT2)和葡萄糖转运载体1、2(GLUT1、2)、小肽转运载体1、2(PepT1、2)和葡萄糖转运载体葡萄糖转运载体1、2、3(GLUT1、2、3)的mRNA相对表达量均显著低于对照组(P<0.05)。结论:妊娠期暴露氯氮平通过影响各类营养物质的转运载体细胞的mRNA表达水平,降低转运载体蛋白的营养物质转运功能,从而对胎儿的生长发育有着较为严重的危害。

Objective To investigate the effect of exposure to clozapine during pregnancy on fetal nutrient transport and its mechanism.Method Twenty-six pregnant women with clozapine exposure admitted to the department of Obstetrics and Gynecology of our hospital from June 2018 to June 2020 were selected as the research object,and another twenty-six pregnant women with normal full-term natural delivery or cesarean section were included in the control group.The serological indexes of the two groups were compared.The levels of nutrients in trophoblast cells of placental tissue were determined by ELISA.The relative expression levels of each transporter protein gene were determined by real-time quantitative RT-PCR and compared.Results Serum albumin,glucose and alkaline phosphatase in observation group were significantly lower than those in normal group(P<0.05),and serum ammonia level was significantly higher than that in normal group(P<0.05).The levels of threonine,valine,isoleucine,histidine,asparagine and glycine in observation group were lower than those in normal group,and the differences were statistically significant(P<0.05).Observation group of amino acid transport carrier in the placenta tissue neutral amino acid transport carrier 1,2(SNAT1,2),3(EAAT3)glutamate transport carrier,l-type amino acid transport carrier 2 carrier(LAT2)and glucose transporter1,2(GLUT1,2),the small peptide transport carrier 1,2(PepT1,2)glucose and glucose transport vehicles,the mRNA relative expression levels of transporters1,2 and 3(GLUT1,2and3)were significantly lower than those of control group(P<0.05).Conclusion Exposure to clozapine during pregnancy can affect the mRNA expression level of transporter cells of various nutrients and reduce the nutrient transport function of transporter proteins,thus causing serious harm to fetal growth and development.