葡萄糖调节蛋白78在胎盘滋养细胞中的表达及其与妊娠期糖尿病发病的关系

Expression of glucose regulated protein 78 and the pathogenesis of gestational diabetes mellitus

目的探讨葡萄糖调节蛋白78（GRP78）在妊娠期糖尿病（GDM）孕妇胎盘滋养细胞中的表达及其与GDM发病的关系。方法选择2013年5月--2014年5月在青岛市市立医院住院分娩的GDM孕妇50例（GDM组），同期人院分娩的健康孕妇50例（健康孕妇组），两组孕妇均因臀位、骨盆狭窄、瘢痕子宫或社会因素行剖宫产术分娩。采用实时荧光定量PCR技术检测胎盘滋养细胞中GRP78mRNA的表达；采用免疫组化非生物素二步法检测胎盘滋养细胞中GRP78蛋白的定性表达，依据细胞染色强度进行分级。结果（1）GDM组及健康孕妇组胎盘滋养细胞中均有GRP78mRNA的表达，GDM组胎盘滋养细胞中GRP78mRNA的相对表达水平为15．6±0．4，健康孕妇组胎盘滋养细胞中GRP78mRNA相对表达水平为6．0±0．7，GDM组GRP78mRNA的相对表达水平是健康孕妇组的2．6倍，两组比较，差异有统计学意义（P〈0．01）。（2）GDM组孕妇胎盘滋养细胞的胞质中有大量的GRP78蛋白阳性表达颗粒，呈深、浅棕色或黄色染色，GDM组GRP78蛋白的强阳性表达率为96％（48／50）；健康孕妇组胎盘滋养细胞的胞质中有少量的GRP78蛋白阳性表达颗粒，主要为黄色染色的弱阳性表达（38例），呈浅棕色染色的强阳性表达仅11例，健康孕妇组GRP78蛋白的强阳性表达率为22％（11／50）。两组孕妇GRP78蛋白的强阳性表达率比较，差异有统计学意义（P〈0．01）。结论GRP78在GDM孕妇的胎盘滋养细胞中高表达，可能与GDM的发病有关。

Objective To investigate the relationship between the expression of glucose regulated protein 78 （GRP78） in the placental trophoblast cells and the pathogenesis of gestational diabetes mellitus （GDM）. Methods All the patients were recruited from Qingdao Municipal Hospital from May 2013 to May 2014. Among them, fifty women with GDM were assigned to the GDM group, and fifty healthy women were defined as the control group. All of them received cesarean section because of breech presentation, contracted pelvis, scarred uterus or on mother＇s demand. Real-time PCR was conducted to analyze the expression of GRP78 mRNA in the trophoblasts. Immunohistoehemistry was performed to detect the localization of GRP78 protein in the placentasl trophoblast ceils. Results （1） GRP78 mRNA expressed in the cytoplasm of trophoblasts of both the GDM group and the control group. The GRP78 mRNA levels in the GDM group and the control group were 15.6_＋0.4 and 6.0_＋0.7, respectively. The relative expression level of GRP78 mRNA in the GDM group was 2.6 times of that in the control group, with statistically significant difference （P〈0.01）. （2） The expression of GRP78 protein was found in the cytoplasm of the trophoblasts of the GDM group. It showed in deep, light brown or yellow after staining, according to the expression degree. The expression of GRP78 protein was also found in the cytoplasm of the trophoblasts of the control group, but it mainly showed yellow color （38/50）. The strong positive rate of GRP78 protein in the GDM group （96%, 48/50） was higher than that in the control group （22%, 11/50; P〈0.01）. Conclusion The expression of GRP78 increased in the placental trophoblast cells of GDM patients. It might suggest that GRP78 had some effect on the pathogenesis of GDM.