
国际妇产科学杂志 ›› 2025, Vol. 52 ›› Issue (4): 366-370.doi: 10.12280/gjfckx.20250297
收稿日期:2025-03-24
出版日期:2025-08-15
发布日期:2025-09-08
通讯作者:
王永红,E-mail:作者简介:△审校者
基金资助:
YANG Yao-yao, WANG Yong-hong△(
)
Received:2025-03-24
Published:2025-08-15
Online:2025-09-08
Contact:
WANG Yong-hong, E-mail: 摘要:
子痫前期(preeclampsia,PE)是一种妊娠期特有的多系统功能障碍性疾病,其特征为妊娠20周后新发高血压、蛋白尿等,严重时可进展为子痫,是全球范围内孕产妇和新生儿预后不良甚至死亡的重要原因之一。PE发病机制复杂,涉及胎盘发育异常、血管内皮功能障碍、氧化应激失衡等多种病理生理过程。近年研究发现,自噬作为细胞重要的稳态调控机制,通过溶酶体途径降解受损细胞器、错误折叠蛋白,在PE发生发展中发挥关键作用。具体而言,自噬通过调控滋养细胞侵袭能力、子宫螺旋动脉重塑过程、氧化应激水平、炎症反应强度以及内质网应激状态等多个环节参与PE的病理进程。值得注意的是,多种信号分子和药物可通过调节自噬活性影响PE的疾病进展,为开发新型靶向治疗策略提供了理论依据。综述自噬在PE发病机制中的分子作用及其治疗潜力,旨在为深入理解PE的病理机制和临床防治提供新视角。
杨瑶瑶, 王永红. 自噬在子痫前期发病中的作用机制及相关治疗进展[J]. 国际妇产科学杂志, 2025, 52(4): 366-370.
YANG Yao-yao, WANG Yong-hong. Research Progress on the Mechanism of Autophagy in the Pathogenesis of Preeclampsia and Related Treatments[J]. Journal of International Obstetrics and Gynecology, 2025, 52(4): 366-370.
| [1] | Cheng K, Cui J, Zhou W, et al. miRNA-141-5p Affects the Levels of Neutrophil Elastase in Preeclampsia by Regulating MAPK1[J]. Maternal-Fetal Medicine, 2022, 4(4):238-244. doi:10.1097/FM9.0000000000000169. |
| [2] | Komijani E, Parhizkar F, Abdolmohammadi-Vahid S, et al. Autophagy-mediated immune system regulation in reproductive system and pregnancy-associated complications[J]. J Reprod Immunol, 2023, 158:103973. doi: 10.1016/j.jri.2023.103973. |
| [3] |
Kasimanickam R, Kasimanickam V. MicroRNAs in the Pathogenesis of Preeclampsia-A Case-Control In Silico Analysis[J]. Curr Issues Mol Biol, 2024, 46(4):3438-3459. doi: 10.3390/cimb46040216.
pmid: 38666946 |
| [4] | Sato K. Multiple roles of endocytosis and autophagy in intracellular remodeling during oocyte-to-embryo transition[J]. Proc Jpn Acad Ser B Phys Biol Sci, 2022, 98(5):207-221. doi: 10.2183/pjab.98.013. |
| [5] |
Sun F, Ali NN, Londoño-Vásquez D, et al. Increased DNA damage in full-grown oocytes is correlated with diminished autophagy activation[J]. Nat Commun, 2024, 15(1):9463. doi: 10.1038/s41467-024-53559-w.
pmid: 39487138 |
| [6] | Lu H, Yang HL, Zhou WJ, et al. Rapamycin prevents spontaneous abortion by triggering decidual stromal cell autophagy-mediated NK cell residence[J]. Autophagy, 2021, 17(9):2511-2527. doi: 10.1080/15548627.2020.1833515. |
| [7] | Liu S, Hong L, Lian R, et al. Transcriptomic Analysis Reveals Endometrial Dynamics in Normoweight and Overweight/Obese Polycystic Ovary Syndrome Women[J]. Front Genet, 2022, 13:874487. doi: 10.3389/fgene.2022.874487. |
| [8] | Kotzur R, Kahlon S, Isaacson B, et al. Pregnancy trained decidual NK cells protect pregnancies from harmful Fusobacterium nucleatum infection[J]. PLoS Pathog, 2024, 20(1):e1011923. doi: 10.1371/journal.ppat.1011923. |
| [9] | Nakashima A, Furuta A, Yamada K, et al. The Role of Autophagy in the Female Reproduction System: For Beginners to Experts in This Field[J]. Biology(Basel), 2023, 12(3):373. doi: 10.3390/biology12030373. |
| [10] |
Nakashima A, Yamanaka-Tatematsu M, Fujita N, et al. Impaired autophagy by soluble endoglin, under physiological hypoxia in early pregnant period, is involved in poor placentation in preeclampsia[J]. Autophagy, 2013, 9(3):303-316. doi: 10.4161/auto.22927.
pmid: 23321791 |
| [11] | Cheng S, Huang Z, Jash S, et al. Hypoxia-Reoxygenation Impairs Autophagy-Lysosomal Machinery in Primary Human Trophoblasts Mimicking Placental Pathology of Early-Onset Preeclampsia[J]. Int J Mol Sci, 2022, 23(10):5644. doi: 10.3390/ijms23105644. |
| [12] | Zhang Y, Ruan LL, Li MR, et al. Palmitic acid impairs human and mouse placental function by inhibiting trophoblast autophagy through induction of acyl-coenzyme A-binding protein (ACBP) upregulation[J]. Hum Reprod, 2024:deae091. doi: 10.1093/humrep/deae091. |
| [13] | Chen G, Chen L, Huang Y, et al. Increased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells[J]. Bioengineered, 2022, 13(2):3620-3633. doi: 10.1080/21655979.2021.1997132. |
| [14] | Sun J, Yu M, Du W, et al. The cGAS-STING pathway promotes the development of preeclampsia by upregulating autophagy: Mechanisms and implications[J]. Int Immunopharmacol, 2024, 128:111531. doi: 10.1016/j.intimp.2024.111531. |
| [15] | Ma F, Ding N, Xie L, et al. Inhibition of autophagy via 3-methyladenine alleviates the progression of preeclampsia[J]. Acta Biochim Biophys Sin(Shanghai), 2024, 57(3):356-364. doi: 10.3724/abbs.2024096. |
| [16] |
Huang Z, Cheng S, Jash S, et al. Exploiting sweet relief for preeclampsia by targeting autophagy-lysosomal machinery and proteinopathy[J]. Exp Mol Med, 2024, 56(5):1206-1220. doi: 10.1038/s12276-024-01234-x.
pmid: 38760513 |
| [17] | Hu H, Chen W, Tao Z, et al. Cyclosporin A alleviates trophoblast apoptosis and senescence by promoting autophagy in preeclampsia[J]. Placenta, 2022, 117:95-108. doi: 10.1016/j.placenta.2021.11.003. |
| [18] |
Chu Y, Zhu C, Yue C, et al. Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes the proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway[J]. Cell Biosci, 2021, 11(1):182. doi: 10.1186/s13578-021-00681-7.
pmid: 34645519 |
| [19] | Chu N, Tang Y, Wang CJ, et al. ANP promotes HTR-8/SVneo cell invasion by upregulating protein kinase N 3 via autophagy inhibition[J]. FASEB J, 2023, 37(3):e22779. doi: 10.1096/fj.202200833RRR. |
| [20] | Ortega MA, Garcia-Puente LM, Fraile-Martinez O, et al. Oxidative Stress, Lipid Peroxidation and Ferroptosis Are Major Pathophysiological Signatures in the Placental Tissue of Women with Late-Onset Preeclampsia[J]. Antioxidants(Basel), 2024, 13(5):591. doi: 10.3390/antiox13050591. |
| [21] |
Dimitriadis E, Rolnik DL, Zhou W, et al. Pre-eclampsia[J]. Nat Rev Dis Primers, 2023, 9(1):8. doi: 10.1038/s41572-023-00417-6.
pmid: 36797292 |
| [22] | James JL, Saghian R, Perwick R, et al. Trophoblast plugs: impact on utero-placental haemodynamics and spiral artery remodelling[J]. Hum Reprod, 2018, 33(8):1430-1441. doi: 10.1093/humrep/dey225. |
| [23] |
Park JY, Mani S, Clair G, et al. A microphysiological model of human trophoblast invasion during implantation[J]. Nat Commun, 2022, 13(1):1252. doi: 10.1038/s41467-022-28663-4.
pmid: 35292627 |
| [24] | Jin J, Gao L, Zou X, et al. Gut Dysbiosis Promotes Preeclampsia by Regulating Macrophages and Trophoblasts[J]. Circ Res, 2022, 131(6):492-506. doi: 10.1161/CIRCRESAHA.122.320771. |
| [25] | Nakashima A, Furuta A, Yoshida-Kawaguchi M, et al. Immunological regulation and the role of autophagy in preeclampsia[J]. Am J Reprod Immunol, 2024, 91(3):e13835. doi: 10.1111/aji.13835. |
| [26] | Darmochwal-Kolarz D, Chara A. The Association of IL-17 and PlGF/sENG Ratio in Pre-Eclampsia and Adverse Pregnancy Outcomes[J]. Int J Environ Res Public Health, 2022, 20(1):768. doi: 10.3390/ijerph20010768. |
| [27] | Li Y, Zhao X, He B, et al. Autophagy Activation by Hypoxia Regulates Angiogenesis and Apoptosis in Oxidized Low-Density Lipoprotein-Induced Preeclampsia[J]. Front Mol Biosci, 2021, 8:709751. doi: 10.3389/fmolb.2021.709751. |
| [28] |
Shen J, Teng X, Zhao J, et al. A Potential Autophagy-Related-Gene Based Signature in Patients with Preeclampsia[J]. Front Biosci (Landmark Ed), 2023, 28(7):132. doi: 10.31083/j.fbl2807132.
pmid: 37525915 |
| [29] | Chen Z, Li C, Yuan A, et al. α-Solanine Causes Cellular Dysfunction of Human Trophoblast Cells via Apoptosis and Autophagy[J]. Toxins(Basel), 2021, 13(1):67. doi: 10.3390/toxins13010067. |
| [30] | Ma′ayeh M, Costantine MM. Prevention of preeclampsia[J]. Semin Fetal Neonatal Med, 2020, 25(5):101123. doi: 10.1016/j.siny.2020.101123. |
| [31] | Opichka MA, Livergood MC, Balapattabi K, et al. Mitochondrial targeted antioxidant attenuates preeclampsia-like phenotypes induced by syncytiotrophoblast-specific Gαq signaling[J]. Sci Adv, 2023, 9(48):eadg8118. doi: 10.1126/sciadv.adg8118. |
| [32] | Yildirim RM, Ergun Y, Basar M. Mitochondrial Dysfunction, Mitophagy and Their Correlation with Perinatal Complications: Preeclampsia and Low Birth Weight[J]. Biomedicines, 2022, 10(10):2539. doi: 10.3390/biomedicines10102539. |
| [33] |
Zhou X, Zhao X, Zhou W, et al. Impaired placental mitophagy and oxidative stress are associated with dysregulated BNIP3 in preeclampsia[J]. Sci Rep, 2021, 11(1):20469. doi: 10.1038/s41598-021-99837-1.
pmid: 34650122 |
| [34] | Guerby P, Tasta O, Swiader A, et al. Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia[J]. Redox Biol, 2021, 40:101861. doi: 10.1016/j.redox.2021.101861. |
| [35] | Wang P, Huang CX, Gao JJ, et al. Resveratrol induces SIRT1-Dependent autophagy to prevent H2O2-Induced oxidative stress and apoptosis in HTR8/SVneo cells[J]. Placenta, 2020, 91:11-18. doi: 10.1016/j.placenta.2020.01.002. |
| [36] | Gu S, Zhou C, Pei J, et al. Esomeprazole inhibits hypoxia/endothelial dysfunction-induced autophagy in preeclampsia[J]. Cell Tissue Res, 2022, 388(1):181-194. doi: 10.1007/s00441-022-03587-z. |
| [37] | Xu J, Yang KC, Go NE, et al. Chloroquine treatment induces secretion of autophagy-related proteins and inclusion of Atg8-family proteins in distinct extracellular vesicle populations[J]. Autophagy, 2022, 18(11):2547-2560. doi: 10.1080/15548627.2022.2039535. |
| [38] |
Denkl B, Cordasic N, Huebner H, et al. No evidence of the unfolded protein response in the placenta of two rodent models of preeclampsia and intrauterine growth restriction[J]. Biol Reprod, 2021, 105(2):449-463. doi: 10.1093/biolre/ioab087.
pmid: 33955453 |
| [39] | Cheng S, Huang Z, Banerjee S, et al. Evidence From Human Placenta, Endoplasmic Reticulum-Stressed Trophoblasts, Transgenic Mice Links Transthyretin Proteinopathy to Preeclampsia[J]. Hypertension, 2022, 79(8):1738-1754. doi: 10.1161/HYPERTENSIONAHA.121.18916. |
| [40] |
Ji L, Zhang X, Chen Z, et al. High glucose-induced p66Shc mitochondrial translocation regulates autophagy initiation and autophagosome formation in syncytiotrophoblast and extravillous trophoblast[J]. Cell Commun Signal, 2024, 22(1):234. doi: 10.1186/s12964-024-01621-x.
pmid: 38643181 |
| [41] | Cheng SB, Nakashima A, Huber WJ, et al. Pyroptosis is a critical inflammatory pathway in the placenta from early onset preeclampsia and in human trophoblasts exposed to hypoxia and endoplasmic reticulum stressors[J]. Cell Death Dis, 2019, 10(12):927. doi: 10.1038/s41419-019-2162-4. |
| [42] |
Ribeiro VR, Romao-Veiga M, Nunes PR, et al. Increase of autophagy marker p62 in the placenta from pregnant women with preeclampsia[J]. Hum Immunol, 2022, 83(5):447-452. doi: 10.1016/j.humimm.2022.02.005.
pmid: 35210117 |
| [43] | Zhou C, Ding Y, Yu L, et al. Melatonin regulates proliferation, apoptosis and invasion of trophoblasts in preeclampsia by inhibiting endoplasmic reticulum stress[J]. Am J Reprod Immunol, 2022, 88(2):e13585. doi: 10.1111/aji.13585. |
| [44] |
Li J, Zhang T, Ren T, et al. Oxygen-sensitive methylation of ULK1 is required for hypoxia-induced autophagy[J]. Nat Commun, 2022, 13(1):1172. doi: 10.1038/s41467-022-28831-6.
pmid: 35246531 |
| [45] | Li Y, Guo Y, Wu D, et al. Phenylbutyric acid inhibits hypoxiainduced trophoblast apoptosis and autophagy in preeclampsia via the PERK/ATF-4/CHOP pathway[J]. Mol Reprod Dev, 2024, 91(4):e23742. doi: 10.1002/mrd.23742. |
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