调节性细胞死亡在子痫前期中的作用
The Role of Regulatory Cell Death in Preeclampsia
DOI: 10.12677/acm.2025.1541145, PDF,   
作者: 马佳宁：山东大学第二医院检验医学中心，山东 济南
关键词: 子痫前期；调节性细胞死亡；凋亡；自噬；焦亡；铁死亡；铜死亡；Preeclampsia； Regulated Cell Death； Apoptosis； Autophagy； Pyroptosis； Ferroptosis； Cuprotosis
摘要: 子痫前期是一种发病机制复杂的妊娠期疾病，可能涉及到多种调节性细胞死亡方式，如细胞凋亡、自噬、焦亡、铁死亡和铜死亡等。将子痫前期与调节性细胞死亡联系起来，有助于更加全面深入地了解子痫前期的病理进程，为子痫前期的发生提供潜在的预测指标和新型诊疗方法。本文就近年来调节性细胞死亡与子痫前期的研究进展进行综述。
Abstract: Preeclampsia is a pregnancy disease with a complex pathogenesis, which may involve multiple regulatory cell death modes such as apoptosis, autophagy, pyroptosis, ferroptosis, and copper death. Linking preeclampsia with regulatory cell death can help to gain a more comprehensive and in-depth understanding of the pathological process of preeclampsia, providing potential predictive indicators and novel diagnostic and therapeutic methods for its occurrence. This article reviews the research progress on regulatory cell death and preeclampsia in recent years.
文章引用：马佳宁. 调节性细胞死亡在子痫前期中的作用[J]. 临床医学进展, 2025, 15(4): 1983-1988. https://doi.org/10.12677/acm.2025.1541145

参考文献

[1] Jung, E., Romero, R., Yeo, L., Gomez-Lopez, N., Chaemsaithong, P., Jaovisidha, A., et al. (2022) The Etiology of Preeclampsia. American Journal of Obstetrics and Gynecology, 226, S844-S866. [Google Scholar] [CrossRef] [PubMed]
[2] 中华医学会妇产科学分会妊娠期高血压疾病学组. 妊娠期高血压疾病诊治指南(2020) [J]. 中华妇产科杂志, 2020, 55(4): 227-238.
[3] Wu, Q., Ying, X., Yu, W., Li, H., Wei, W., Lin, X., et al. (2024) Comparison of Immune‐Related Gene Signatures and Immune Infiltration Features in Early‐ and Late‐Onset Preeclampsia. The Journal of Gene Medicine, 26, e3676. [Google Scholar] [CrossRef] [PubMed]
[4] Abalos, E., Cuesta, C., Carroli, G., Qureshi, Z., Widmer, M., Vogel, J., et al. (2014) Pre‐Eclampsia, Eclampsia and Adverse Maternal and Perinatal Outcomes: A Secondary Analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG: An International Journal of Obstetrics & Gynaecology, 121, 14-24. [Google Scholar] [CrossRef] [PubMed]
[5] Brown, M.A., Magee, L.A., Kenny, L.C., Karumanchi, S.A., McCarthy, F.P., Saito, S., et al. (2018) Hypertensive Disorders of Pregnancy. Hypertension, 72, 24-43. [Google Scholar] [CrossRef] [PubMed]
[6] Ali, M., Ahmed, M., Memon, M., Chandio, F., Shaikh, Q., Parveen, A., et al. (2024) Preeclampsia: A Comprehensive Review. Clinica Chimica Acta, 563, Article ID: 119922. [Google Scholar] [CrossRef] [PubMed]
[7] Galluzzi, L., Vitale, I., Aaronson, S.A., et al. (2018) Molecular Mechanisms of Cell Death: Recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death and Differentiation, 25, 486-541.
[8] Vitale, I., et al. (2023) Apoptotic Cell Death in Disease—Current Understanding of the NCCD 2023. Cell Death and Differentiation, 30, 1097-1154.
[9] Newton, K., Strasser, A., Kayagaki, N. and Dixit, V.M. (2024) Cell Death. Cell, 187, 235-256. [Google Scholar] [CrossRef] [PubMed]
[10] Lokeswara, A.W., Hiksas, R., Irwinda, R. and Wibowo, N. (2021) Preeclampsia: From Cellular Wellness to Inappropriate Cell Death, and the Roles of Nutrition. Frontiers in Cell and Developmental Biology, 9, Article ID: 726513. [Google Scholar] [CrossRef] [PubMed]
[11] Kerr, J.F.R., Wyllie, A.H. and Currie, A.R. (1972) Apoptosis: A Basic Biological Phenomenon with Wide-Ranging Implications in Tissue Kinetics. British Journal of Cancer, 26, 239-257. [Google Scholar] [CrossRef] [PubMed]
[12] Liu, L., Zhou, L., Wang, L., Zheng, P., Zhang, F., Mao, Z., et al. (2023) Programmed Cell Death in Asthma: Apoptosis, Autophagy, Pyroptosis, Ferroptosis, and Necroptosis. Journal of Inflammation Research, 16, 2727-2754. [Google Scholar] [CrossRef] [PubMed]
[13] Hojo, T., Skarzynski, D.J. and Okuda, K. (2022) Apoptosis, Autophagic Cell Death, and Necroptosis: Different Types of Programmed Cell Death in Bovine Corpus Luteum Regression. Journal of Reproduction and Development, 68, 355-360. [Google Scholar] [CrossRef] [PubMed]
[14] Heydarnezhad Asl, M., Pasban Khelejani, F., Bahojb Mahdavi, S.Z., Emrahi, L., Jebelli, A. and Mokhtarzadeh, A. (2022) The Various Regulatory Functions of Long Noncoding RNAs in Apoptosis, Cell Cycle, and Cellular Senescence. Journal of Cellular Biochemistry, 123, 995-1024. [Google Scholar] [CrossRef] [PubMed]
[15] Ames, E.G. and Thoene, J.G. (2022) Programmed Cell Death in Cystinosis. Cells, 11, Article No. 670. [Google Scholar] [CrossRef] [PubMed]
[16] Bakrania, B.A., George, E.M. and Granger, J.P. (2022) Animal Models of Preeclampsia: Investigating Pathophysiology and Therapeutic Targets. American Journal of Obstetrics and Gynecology, 226, S973-S987. [Google Scholar] [CrossRef] [PubMed]
[17] Redman, C. (2014) The Six Stages of Pre-Eclampsia. Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health, 4, Article No. 246. [Google Scholar] [CrossRef] [PubMed]
[18] Redman, C.W.G. and Sargent, I.L. (2009) Placental Stress and Pre-Eclampsia: A Revised View. Placenta, 30, 38-42. [Google Scholar] [CrossRef] [PubMed]
[19] Zhou, J., Zhao, Y., An, P., Zhao, H., Li, X. and Xiong, Y. (2023) Hsa_circ_0002348 Regulates Trophoblast Proliferation and Apoptosis through miR-126-3p/BAK1 Axis in Preeclampsia. Journal of Translational Medicine, 21, Article No. 509. [Google Scholar] [CrossRef] [PubMed]
[20] Chen, H., Li, R., Bian, J., Li, X., Su, C., Wang, Y., et al. (2024) OLFML3 Suppresses Trophoblast Apoptosis via the PI3K/AKT Pathway: A Possible Therapeutic Target in Preeclampsia. Placenta, 147, 1-11. [Google Scholar] [CrossRef] [PubMed]
[21] Zuo, Q., Zou, Y., Huang, S., Wang, T., Xu, Y., Zhang, T., et al. (2021) Aspirin Reduces Sflt-1-Mediated Apoptosis of Trophoblast Cells in Preeclampsia. Molecular Human Reproduction, 27, gaaa089. [Google Scholar] [CrossRef] [PubMed]
[22] de Duve, C. and Wattiaux, R. (1966) Functions of Lysosomes. Annual Review of Physiology, 28, 435-492. [Google Scholar] [CrossRef] [PubMed]
[23] Kawamata, T., Kamada, Y., Kabeya, Y., Sekito, T. and Ohsumi, Y. (2008) Organization of the Pre-Autophagosomal Structure Responsible for Autophagosome Formation. Molecular Biology of the Cell, 19, 2039-2050. [Google Scholar] [CrossRef] [PubMed]
[24] Yoshii, S.R. and Mizushima, N. (2017) Monitoring and Measuring Autophagy. International Journal of Molecular Sciences, 18, Article No. 1865. [Google Scholar] [CrossRef] [PubMed]
[25] Nakashima, A., Shima, T., Aoki, A., Kawaguchi, M., Yasuda, I., Tsuda, S., et al. (2020) Placental Autophagy Failure: A Risk Factor for Preeclampsia. Journal of Obstetrics and Gynaecology Research, 46, 2497-2504. [Google Scholar] [CrossRef] [PubMed]
[26] Nakashima, A., Cheng, S., Ikawa, M., Yoshimori, T., Huber, W.J., Menon, R., et al. (2019) Evidence for Lysosomal Biogenesis Proteome Defect and Impaired Autophagy in Preeclampsia. Autophagy, 16, 1771-1785. [Google Scholar] [CrossRef] [PubMed]
[27] Gu, S., Zhou, C., Pei, J., Wu, Y., Wan, S., Zhao, X., et al. (2022) Esomeprazole Inhibits Hypoxia/Endothelial Dysfunction-Induced Autophagy in Preeclampsia. Cell and Tissue Research, 388, 181-194. [Google Scholar] [CrossRef] [PubMed]
[28] Zychlinsky, A., Prevost, M.C. and Sansonetti, P.J. (1992) Shigella Flexneri Induces Apoptosis in Infected Macrophages. Nature, 358, 167-169. [Google Scholar] [CrossRef] [PubMed]
[29] Cookson, B.T. and Brennan, M.A. (2001) Pro-Inflammatory Programmed Cell Death. Trends in Microbiology, 9, 113-114. [Google Scholar] [CrossRef] [PubMed]
[30] Monack, D.M., Navarre, W.W. and Falkow, S. (2001) Salmonella-Induced Macrophage Death: The Role of Caspase-1 in Death and Inflammation. Microbes and Infection, 3, 1201-1212. [Google Scholar] [CrossRef] [PubMed]
[31] Yu, P., Zhang, X., Liu, N., Tang, L., Peng, C. and Chen, X. (2021) Pyroptosis: Mechanisms and Diseases. Signal Transduction and Targeted Therapy, 6, Article No. 128. [Google Scholar] [CrossRef] [PubMed]
[32] 温金, 李宁, 李梓汇, 等. 细胞焦亡与不良妊娠结局关系研究进展[J]. 山东第一医科大学(山东省医学科学院)学报, 2023, 44(1): 10-14.
[33] Quan, X., Ye, J., Yang, X. and Xie, Y. (2021) Hoxa9-Induced Chemerin Signals through CMKLR1/AMPK/TXNIP/ NLRP3 Pathway to Induce Pyroptosis of Trophoblasts and Aggravate Preeclampsia. Experimental Cell Research, 408, Article ID: 112802. [Google Scholar] [CrossRef] [PubMed]
[34] Liu, J. and Yang, W. (2023) Mechanism of Histone Deacetylase HDAC2 in FOXO3-Mediated Trophoblast Pyroptosis in Preeclampsia. Functional & Integrative Genomics, 23, Article No. 152. [Google Scholar] [CrossRef] [PubMed]
[35] Wu, H., liu, K. and Zhang, J. (2022) LINC00240/miR-155 Axis Regulates Function of Trophoblasts and M2 Macrophage Polarization via Modulating Oxidative Stress-Induced Pyroptosis in Preeclampsia. Molecular Medicine, 28, Article No. 119. [Google Scholar] [CrossRef] [PubMed]
[36] Dixon, S.J., Lemberg, K.M., Lamprecht, M.R., Skouta, R., Zaitsev, E.M., Gleason, C.E., et al. (2012) Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death. Cell, 149, 1060-1072. [Google Scholar] [CrossRef] [PubMed]
[37] Stockwell, B.R., Friedmann Angeli, J.P., Bayir, H., Bush, A.I., Conrad, M., Dixon, S.J., et al. (2017) Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell, 171, 273-285. [Google Scholar] [CrossRef] [PubMed]
[38] Ingold, I., Berndt, C., Schmitt, S., et al. (2017) Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis. Cell, 172, 409-422.e21.
[39] Gumilar, K.E., Priangga, B., Lu, C., Dachlan, E.G. and Tan, M. (2023) Iron Metabolism and Ferroptosis: A Pathway for Understanding Preeclampsia. Biomedicine & Pharmacotherapy, 167, Article ID: 115565. [Google Scholar] [CrossRef] [PubMed]
[40] Ng, S., Norwitz, S.G. and Norwitz, E.R. (2019) The Impact of Iron Overload and Ferroptosis on Reproductive Disorders in Humans: Implications for Preeclampsia. International Journal of Molecular Sciences, 20, Article No. 3283. [Google Scholar] [CrossRef] [PubMed]
[41] Zhang, H., He, Y., Wang, J., Chen, M., Xu, J., Jiang, M., et al. (2020) Mir-30-5p-Mediated Ferroptosis of Trophoblasts Is Implicated in the Pathogenesis of Preeclampsia. Redox Biology, 29, Article ID: 101402. [Google Scholar] [CrossRef] [PubMed]
[42] Yang, X., Ding, Y., Sun, L., Shi, M., Zhang, P., Huang, Z., et al. (2022) Ferritin Light Chain Deficiency-Induced Ferroptosis Is Involved in Preeclampsia Pathophysiology by Disturbing Uterine Spiral Artery Remodelling. Redox Biology, 58, Article ID: 102555. [Google Scholar] [CrossRef] [PubMed]
[43] Xu, X., Zhu, M., Zu, Y., Wang, G., Li, X. and Yan, J. (2024) Nox2 Inhibition Reduces Trophoblast Ferroptosis in Preeclampsia via the STAT3/GPX4 Pathway. Life Sciences, 343, Article ID: 122555. [Google Scholar] [CrossRef] [PubMed]
[44] Tsvetkov, P., Coy, S., Petrova, B., Dreishpoon, M., Verma, A., Abdusamad, M., et al. (2022) Copper Induces Cell Death by Targeting Lipoylated TCA Cycle Proteins. Science, 375, 1254-1261. [Google Scholar] [CrossRef] [PubMed]
[45] Zhao, G., Sun, H., Zhang, T. and Liu, J. (2020) Copper Induce Zebrafish Retinal Developmental Defects via Triggering Stresses and Apoptosis. Cell Communication and Signaling, 18, Article No. 45. [Google Scholar] [CrossRef] [PubMed]
[46] Sak, S., Barut, M., Çelik, H., Incebiyik, A., Ağaçayak, E., Uyanikoglu, H., et al. (2018) Copper and Ceruloplasmin Levels Are Closely Related to the Severity of Preeclampsia. The Journal of Maternal-Fetal & Neonatal Medicine, 33, 96-102. [Google Scholar] [CrossRef] [PubMed]
[47] Zhong, Z., Yang, Q., Sun, T. and Wang, Q. (2022) A Global Perspective of Correlation between Maternal Copper Levels and Preeclampsia in the 21st Century: A Systematic Review and Meta-Analysis. Frontiers in Public Health, 10, Article ID: 924103. [Google Scholar] [CrossRef] [PubMed]
[48] Song, X., Li, B., Li, Z., Wang, J. and Zhang, D. (2017) High Serum Copper Level Is Associated with an Increased Risk of Preeclampsia in Asians: A Meta-Analysis. Nutrition Research, 39, 14-24. [Google Scholar] [CrossRef] [PubMed]
[49] Tang, X., Liu, Y. and Zhang, Y. (2024) Novel Cuproptosis-Related Prognostic Gene Profiles in Preeclampsia. BMC Pregnancy and Childbirth, 24, Article No. 53. [Google Scholar] [CrossRef] [PubMed]
[50] Shen, X., Huang, J., Chen, L., Sha, M., Gao, J. and Xin, H. (2024) Blocking Lactate Regulation of the Grhl2/SLC31A1 Axis Inhibits Trophoblast Cuproptosis and Preeclampsia Development. Journal of Assisted Reproduction and Genetics, 41, 3201-3212. [Google Scholar] [CrossRef] [PubMed]

为你推荐