目的：评估早期妊娠和中期妊娠血清性激素结合球蛋白（sex hormone-binding globulin,SHBG）浓度与妊娠期糖尿病（gestational miabetes mellitus,GDM）风险之间的关系,以及SHBG对滋养细胞生物学行为的影响。方法：选取2020年3月―2022年3月在陕西中医药大学第二附属医院接受产前检查时处于早期妊娠（14周之前）或中期妊娠（14~28周）的65名GDM患者（病例组）与130名健康孕妇（对照组）作为研究对象。采用ELISA试剂盒测量血清SHBG水平。体外实验选择滋养细胞系HTR-8/SVneo为研究对象,分为高糖（HG）组和对照组[正常葡萄糖（NG）组]。HG组细胞转染SHBG质粒或载体对照（Vector）。分别通过细胞计数试剂盒、伤口愈合试验、Transwell实验考察细胞的增殖、迁移和侵袭。结果：与对照组相比,GDM组的血清SHBG浓度明显更高。同时,随后发展为GDM的孕妇在早期妊娠显示出明显高于对照组的血清SHBG浓度。逻辑回归分析显示,血清SHBG最低三分位数发生GDM的调整OR为2.74（95%CI：1.17~6.43）。此外,血清SHBG每降低一个标准差,GDM的多变量调整OR为1.49（95%CI：1.05~2.12）。与NG组相比,HG组HTR8/SVneo细胞中SHBG的表达降低,细胞活力下降,细胞迁移和侵袭减弱。与HG+Vector组相比,HG+SHBG组HTR8/SVneo细胞中SHBG的表达上调,细胞活力升高,细胞迁移和侵袭增强。结论：早期妊娠中血清SHBG浓度较低的孕妇患GDM的风险明显增加,并且SHBG上调促进了HG背景下滋养细胞的增殖和迁移。
Abstract
Objective To assess the relationship between serum sex hormone-binding globulin (SHBG) concentrations and the risk of gestational diabetes mellitus (GDM) in early and midterm pregnancies and the effect of SHBG on the biological behavior of trophoblast cells. Methods During the period from March 2020 to March 2022, 65 GDM patients (case group) and 130 healthy pregnant women (control group) who were in early pregnancy (before 14 weeks) or middle pregnancy (14-28 weeks) were selected as the research objects. Serum SHBG level was measured by ELISA kit. In vitro, the trophoblast cell line HTR-8/SVneo was selected as the research object, which was divided into high glucose (HG) group and control group [normal glucose (NG) group]. HG group cells were transfected with SHBG plasmid or Vector. Cell proliferation, migration and invasion were investigated by cell counting kit, wound healing test and Transwell test. Results Serum SHBG concentrations were significantly higher in the GDM group compared to the control group. Also, pregnant women who subsequently developed GDM showed significantly higher serum SHBG concentrations in early pregnancy than controls. Logistic regression analysis showed an adjusted OR of 2.74(95%CI: 1.17-6.43) for the occurrence of GDM in the lowest tertile of serum SHBG. In addition, the multivariate adjusted OR for GDM was 1.49(95%CI: 1.05-2.12) for each standard deviation reduction in serum SHBG. Compared with the NG group, the HG group showed reduced expression of SHBG in HTR8/SVneo cells, decreased cell viability, and diminished cell migration and invasion. Compared with the HG+Vector group, the expression of SHBG in HTR8/SVneo cells was upregulated, cell viability was increased, and cell migration and invasion were enhanced in the HG+SHBG group. Conclusions The risk of GDM in pregnant women with low serum SHBG concentration increases significantly, and the up-regulation of SHBG promotes the proliferation and migration of trophoblasts in HG background.
关键词
性激素结合球蛋白 /
早期妊娠 /
中期妊娠 /
妊娠合并糖尿病 /
滋养细胞
Key words
sex hormone binding globulin /
early pregnancy /
second trimester pregnancy /
gestational diabetes /
trophoblast
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参考文献
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基金
陕西中医药大学2020年省教育厅专项科研计划（20JK0606）
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