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血清和糖皮质激素调节激酶1在流产和子痫前期中的作用和调控机制

叶晨¹, 吴庆珅¹, 孙晓璇¹, 张晓卿¹, 高路^1,2,*

¹海军军医大学生理学教研室，上海 200433；²上海市辅助生殖与优生重点实验室，上海 200123

摘要

血清和糖皮质激素调节激酶 1 (serum and glucocorticoid-regulated kinase 1, SGK1)是一种丝氨酸/苏氨酸激酶，属于蛋白激酶AGC家族。SGK1几乎表达于所有的组织中，其表达与活性受多种生理及病理生理因素调控，包括糖皮质激素、盐皮质激素、脱水、缺血、高渗性休克和放疗等。在磷酸肌醇3- 激酶 (phosphatidylinositide 3-kinase, PI3K)信号通路激活后，SGK1分别被雷帕霉素机制性靶蛋白复合物2 (mechanistic target of rapamycin complex 2, mTORC2)和3-磷酸肌醇依赖性蛋白激酶1 (3-phosphoinositide-dependent protein kinase-1, PDK1)磷酸化其疏水基序和激酶结构域，从而诱导其激活。激活的SGK1可进一步上调多种离子通道表达，例如Na+、Ca2+、K+和Cl-通道等。此外，SGK1还参与调节多种转录因子(如FKHRL1/FOXO3a、β-catenin、NF-κB和p53)的表达与活性，进而影响细胞增殖、存活、凋亡、物质转运、糖酵解及血管生成等基本细胞过程。因此，SGK1 表达或活性失调被认为与多种疾病的发生相关，包括高血压、肿瘤、自身免疫性疾病和神经退行性疾病等。尤其值得关注的是，SGK1在人子宫内膜上皮呈现高表达，并参与妊娠过程的多环节调控。本文综述了SGK1在流产和子痫前期发病机制中的作用，着重探讨其对上皮钠通道(epithelial sodium channel, ENaC)、NF-κB信号通路、滋养层细胞凋亡以及母胎血管生成的调节机制，并展望了SGK1通过调节免疫细胞功能作为治疗妊娠相关疾病潜在靶点的前景。

关键词： 血清和糖皮质激素调节激酶1; 流产; 子痫前期; 上皮钠通道; NF-κB

The roles and regulatory mechanisms of serum and glucocorticoid-regulated kinase 1 in miscarriage and preeclampsia

YE Chen¹, WU Qing-Shen¹, SUN Xiao-Xuan¹, ZHANG Xiao-Qing¹, GAO Lu^1,2,*

¹Department of Physiology, Naval Medical University, Shanghai 200433, China；²Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200123, China

Abstract

Serum and glucocorticoid-regulated kinase 1 (SGK1) is a serine/threonine kinase belonging to the AGC kinase family. SGK1 is widely expressed in diverse tissues, whose expression and activity are regulated by numerous physiological and pathophysiological factors, including glucocorticoids, mineralocorticoids, dehydration, ischemia, hyperosmotic stress, and radiation therapy. Following activation of the phosphatidylinositide 3-kinase (PI3K) signaling pathway, SGK1 is phosphorylated at its hydrophobic motif by the mechanistic target of rapamycin complex 2 (mTORC2) and at its kinase domain by 3-phosphoinositide-dependent protein kinase-1 (PDK1), thereby inducing its activation. Activated SGK1 subsequently upregulates the expression of various ion channels, such as Na+, Ca2+, K+, and Cl- channels. Furthermore, SGK1 participates in regulating the expression and activity of multiple transcription factors (e.g., FKHRL1/FOXO3a, β-catenin, NF-κB, and p53), thereby influencing fundamental cellular processes including proliferation, survival, apoptosis, substance transport, glycolysis, and angiogenesis. Consequently, dysregulation of SGK1 expression or activity is implicated in the pathogenesis of various diseases, including hypertension, cancer, autoimmune disorders, and neurodegenerative diseases. Of particular note, SGK1 exhibits high expression in the human endometrial epithelium and is involved in the regulation of multiple aspects of pregnancy. This review summarizes the role of SGK1 in the pathogenesis of spontaneous abortion and preeclampsia, with a focus on its regulatory mechanisms involving the epithelial sodium channel (ENaC), the NF-κB signaling pathway, trophoblast cell apoptosis, and maternal-fetal blood vessel formation. We also prospect the potential of SGK1 as a therapeutic target for pregnancy-related disorders by modulating immune cell functions.

Key words: serum and glucocorticoid-regulated kinase 1; miscarriage; preeclampsia; epithelial sodium channel; nuclear factor-κB

收稿日期：　　录用日期：

通讯作者：高路　　E-mail:

DOI: 10.13294/j.aps.2026.0028

引用本文：

叶晨, 吴庆珅, 孙晓璇, 张晓卿, 高路. 血清和糖皮质激素调节激酶1在流产和子痫前期中的作用和调控机制[J]. 生理学报 2026; 78 (2): 367-374.

YE Chen, WU Qing-Shen, SUN Xiao-Xuan, ZHANG Xiao-Qing, GAO Lu. The roles and regulatory mechanisms of serum and glucocorticoid-regulated kinase 1 in miscarriage and preeclampsia. Acta Physiol Sin 2026; 78 (2): 367-374 (in Chinese with English abstract).