收稿日期: 2022-04-18
录用日期: 2022-09-06
网络出版日期: 2022-12-02
基金资助
国家自然科学基金(81973894);黑龙江中医药大学“优秀创新人才支持计划”项目(2018RCL12)
Potential role of SIRT1 in unexplained recurrent spontaneous abortion
Received date: 2022-04-18
Accepted date: 2022-09-06
Online published: 2022-12-02
Supported by
National Natural Science Foundation of China(81973894);Heilongjiang University of Chinese Medicine "Excellent Innovative Talents Support Program" Project(2018RCL12)
不明原因型复发性流产（unexplained recurrent spontaneous abortion，URSA）又称为同种免疫型复发性流产，目前认为其主要的发病机制为母胎界面免疫失衡、滋养细胞侵入异常以及胎盘血管生成异常。现有研究已经揭示了沉默信息调节因子1（sirtuin 1，SIRT1）基因在生殖领域和调节免疫性疾病方面的重要作用，然而关于SIRT1在改善URSA中的作用机制，尚缺乏全面系统的研究。SIRT1可能是通过调节组蛋白和关键转录因子的乙酰化过程，影响机体氧化应激和细胞自噬，从而参与URSA发生发展的众多反馈回路和网络。最终，SIRT1可起到调节滋养层细胞侵入和母胎界面血管生成的作用；同时，可以通过控制促炎细胞因子的产生而改善妊娠期间母体过度的免疫炎症反应。SIRT1的活性决定了其去乙酰化的能力，对于下游通路和蛋白的稳定性至关重要，因此提高其活性对于改善URSA有重要意义。研究表明，二甲双胍与白藜芦醇可以激活SIRT1，对SIRT1及其下游靶蛋白具有保护作用，可能是URSA潜在的治疗剂。该文基于SIRT1功能，综述了SIRT1在URSA发生机制中的潜在作用以及外源性靶向激活SIRT1的药物，以期对临床研究中URSA的预防和治疗提供参考。
刘子维 , 曹雯雯 , 王云瑞 , 冯晓玲 . SIRT1在不明原因型复发性流产中的潜在作用[J]. 上海交通大学学报（医学版）, 2022 , 42(10) : 1466 -1473 . DOI: 10.3969/j.issn.1674-8115.2022.10.013
Unexplained recurrent spontaneous abortion (URSA) is also known as alloimmune recurrent abortion. It is suggested that the main pathogenesis of URSA is immune imbalance at the maternal-fetal interface, abnormal trophoblast invasion and abnormal placental angiogenesis. Existing studies have revealed the important role of SIRT1 gene in the field of reproduction and the regulation of immune diseases. However, there is still a lack of systematic and comprehensive research overview on the mechanism of SIRT1 in improving URSA. SIRT1 may affect oxidative stress and autophagy by regulating the acetylation process of histones and key transcription factors, thus participating in numerous feedback loops and networks of URSA occurrence and development. Finally, SIRT1 can play a role in regulating trophoblast cell invasion and maternal-fetal interface angiogenesis. At the same time, the production of proinflammatory cytokines is suppressed to improve the excessive maternal immune inflammatory response during pregnancy. The activity of SIRT1 determines its deacetylation ability, which is crucial for downstream pathways and protein stability. Therefore, improving its activity is of great significance for improving URSA. Studies have shown that metformin and resveratrol can activate SIRT1 and protect SIRT1 and its downstream target proteins, which may be potential therapeutic agents for URSA. Based on the function of SIRT1, this article reviews the potential role of SIRT1 in the pathogenesis of URSA and the exogenous drugs targeting SIRT1 activation, in order to provide reference for the prevention and treatment of URSA in clinical research.
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