褪黑素与妊娠期高血压疾病的关系研究进展

doi:10.3969/j.issn.1674-8115.2023.10.011

上海交通大学学报（医学版） ›› 2023, Vol. 43 ›› Issue (10): 1297-1303.doi: 10.3969/j.issn.1674-8115.2023.10.011

• 综述 • 上一篇

褪黑素与妊娠期高血压疾病的关系研究进展

陆若玉¹(), 康文慧¹, 赵安达², 陆兆辉³, 李生慧¹()

^1.上海交通大学公共卫生学院，上海 200025
^2.上海交通大学医学院附属第九人民医院营养科，上海 200011
^3.上海儿童医学中心三亚市妇女儿童医院心胸外科，三亚 572000

收稿日期:2023-03-23 接受日期:2023-07-10 出版日期:2023-10-28 发布日期:2023-10-28
通讯作者: 李生慧 E-mail:luruoyu0702@163.com;lsh9907@163.com
作者简介:陆若玉（1999—），女，蒙古族，硕士生；电子信箱：luruoyu0702@163.com。
基金资助:
国家自然科学基金(82273651)

Research progress on the association between melatonin and hypertensive disorder complicating pregnancy

LU Ruoyu¹(), KANG Wenhui¹, ZHAO Anda², LU Zhaohui³, LI Shenghui¹()

^1.School of Public Health, Shanghai Jiao Tong University, Shanghai 200025, China
^2.Department of Nutrition, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
^3.Department of Cardiothoracic Surgery, Sanya Women and Children's Hospital, Shanghai Children's Medical Center, Sanya 572000, China

Received:2023-03-23 Accepted:2023-07-10 Online:2023-10-28 Published:2023-10-28
Contact: LI Shenghui E-mail:luruoyu0702@163.com;lsh9907@163.com
Supported by:
National Natural Science Foundation of China(82273651)

摘要/Abstract

摘要：

褪黑素（N-乙酰基-5-甲氧基色胺）为多效性神经内分泌脂溶性小分子物质，主要由松果体分泌。妊娠期间，孕妇夜间褪黑素水平随着妊娠期的进展而升高，产后恢复正常。妊娠期高血压疾病病因复杂，越来越多的证据表明褪黑素参与妊娠期高血压疾病的调控，该调控与褪黑素表达水平、分泌节律和受体水平存在相关性。胎盘血液循环灌注异常、缺血缺氧和孕妇全身血管内皮功能障碍是妊娠期高血压疾病的主要病理生理过程。褪黑素通过直接抗氧化作用，改善线粒体功能障碍和保护滋养层细胞免受氧化损伤，参与胎盘氧化应激水平调控，在防止胎盘缺氧缺血再灌注引起的氧化损伤中发挥保护作用，从而维持胎盘功能稳态。此外，也有证据显示褪黑素通过减少促炎细胞因子以及血管活性化合物的产生和分泌来保护母体血管内皮免受氧化应激损伤，参与孕妇全身血压的调控。这些发现均提示褪黑素可通过氧化应激的调控参与妊娠期胎盘和全身血管功能稳态的维持。该文以褪黑素对妊娠期高血压疾病的影响及相关机制为切入点进行综述，总结了褪黑素在妊娠期高血压疾病发病进程中所发挥的积极作用。

关键词: 褪黑素, 妊娠期高血压疾病, 胎盘功能不全, 氧化应激, 血管内皮

Abstract:

Melatonin (N-acetyl-5-methoxytryptamine) is a polypotent neuroendocrine lipid-soluble small molecule secreted mainly by the pineal gland. During gestation, melatonin levels in the mother at night rise as the pregnancy progresses and return to normal after delivery. The etiology of hypertensive disorder complicating pregnancy (HDCP) is multifaceted. An increasing number of evidence suggests the involvement of melatonin in the pathogenic process, and the regulation is related to its expression level, secretion rhythm and receptor level. Abnormal placental blood circulation, ischemia and hypoxia and systemic vascular endothelium dysfunction are the main pathological processes of HDCP. Through direct antioxidant effect, melatonin improves mitochondrial dysfunction and protects trophoblast cells from oxidative damage, thus participating in the regulation of placental oxidative stress level, and plays a protective role in preventing oxidative damage caused by hypoxic ischemia reperfusion of placenta, thus maintaining placental functional homeostasis. In addition, there is also evidence that melatonin can protect maternal vascular endothelium from oxidative stress by reducing the production and secretion of pro-inflammatory cytokines and vasoactive compounds, and participating in the regulation of systemic blood pressure in pregnant women. These confidences suggest that melatonin can be involved in the maintenance of placental and systemic vascular functional homeostasis during pregnancy through the regulation of oxidative stress. In this article, the effects of melatonin on HDCP and the related mechanisms are reviewed, and the positive role of melatonin in the pathogenesis of HDCP is summarized.

Key words: melatonin, hypertensive disorder complicating pregnancy (HDCP), placental insufficiency, oxidative stress, vascular endothelium

中图分类号:

R714.252

陆若玉, 康文慧, 赵安达, 陆兆辉, 李生慧. 褪黑素与妊娠期高血压疾病的关系研究进展[J]. 上海交通大学学报（医学版）, 2023, 43(10): 1297-1303.

LU Ruoyu, KANG Wenhui, ZHAO Anda, LU Zhaohui, LI Shenghui. Research progress on the association between melatonin and hypertensive disorder complicating pregnancy[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(10): 1297-1303.

参考文献 55

1	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.
	Hypertensive Disorders in Pregnancy Subgroup, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association. Guidelines for diagnosis and treatment of hypertensive disorders in pregnancy (2020)[J]. Chinese Journal of Obstetrics and Gynecology, 2020, 55(4): 227-238.
2	杨宁, 李玉明. 宽严相济: 孕期血压管理[J]. 中华高血压杂志, 2019, 27(1): 2-4.
	YANG N, LI Y M. Tempering leniency: blood pressure management during pregnancy[J]. Chinese Journal of Hypertension, 2019, 27(1): 2-4.
3	李丽, 付强强. 中国妊娠期高血压疾病患病率的Meta分析[J]. 中国妇幼保健, 2019, 34(14): 3378-3381.
	LI L, FU Q Q. A meta-analysis of the prevalence of hypertensive diseases during pregnancy in China[J]. Maternal and child health care of China, 2019, 34(14): 3378-3381.
4	肖会芬. 妊娠高血压综合征合并胎盘早剥临床探析[J]. 中外医疗, 2014, 33(5): 192-193.
	XIAO H F. Clinical analysis of pregnancy-induced hypertension syndrome with placental abruption[J]. China and foreign medical treatment, 2014, 33(5): 192-193.
5	PARKS W T, CATOV J M. The placenta as a window to maternal vascular health[J]. Obstet Gynecol Clin North Am, 2020, 47(1): 17-28.
6	COX A G, MARSHALL S A, PALMER K R, et al. Current and emerging pharmacotherapy for emergency management of preeclampsia[J]. Expert Opin Pharmacother, 2019, 20(6): 701-712.
7	CHAPPELL L C, CLUVER C A, KINGDOM J, et al. Pre-eclampsia[J]. Lancet, 2021, 398(10297): 341-354.
8	TRANQUILLI A L, DEKKER G, MAGEE L, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP[J]. Pregnancy Hypertens, 2014, 4(2): 97-104.
9	DOMINGUEZ-RODRIGUEZ A, ABREU-GONZALEZ P, REITER R J. Melatonin and cardiovascular disease: myth or reality?[J]. Rev Esp Cardiol (Engl Ed), 2012, 65(3): 215-218.
10	DOMINGUEZ-RODRIGUEZ A, ABREU-GONZALEZ P, ARROYO-UCAR E, et al. Decreased level of melatonin in serum predicts left ventricular remodelling after acute myocardial infarction[J]. J Pineal Res, 2012, 53(3): 319-323.
11	DOMINGUEZ-RODRIGUEZ A, ABREU-GONZALEZ P, SANCHEZ-SANCHEZ J J, et al. Melatonin and circadian biology in human cardiovascular disease[J]. J Pineal Res, 2010, 49(1): 14-22.
12	SIMKO F, PECHANOVA O. Recent trends in hypertension treatment: perspectives from animal studies[J]. J Hypertens Suppl, 2009, 27(6): S1-4.
13	SIMKO F, PAULIS L. Melatonin as a potential antihypertensive treatment[J]. J Pineal Res, 2007, 42(4): 319-322.
14	REITER R J, TAN D X, FUENTES-BROTO L. Melatonin: a multitasking molecule[J]. Prog Brain Res, 2010, 181: 127-151.
15	DOU Y, LIN B, CHENG H, et al. The reduction of melatonin levels is associated with the development of preeclampsia: a meta-analysis[J]. Hypertens Pregnancy, 2019, 38(2): 65-72.
16	FANTASIA I, BUSSOLARO S, STAMPALIJA T, et al. The role of melatonin in pregnancies complicated by placental insufficiency: a systematic review[J]. Eur J Obstet Gynecol Reprod Biol, 2022, 278: 22-28.
17	LANOIX D, GUÉRIN P, VAILLANCOURT C. Placental melatonin production and melatonin receptor expression are altered in preeclampsia: new insights into the role of this hormone in pregnancy[J]. J Pineal Res, 2012, 53(4): 417-425.
18	LÓPEZ-CANUL M, MIN S H, POSA L, et al. Melatonin MT1 and MT2 receptors exhibit distinct effects in the modulation of body temperature across the light/dark cycle[J]. Int J Mol Sci, 2019, 20(10): E2452.
19	GALANO A, TAN D X, REITER R J. On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK[J]. J Pineal Res, 2013, 54(3): 245-257.
20	BARLOW-WALDEN L R, REITER R J, ABE M, et al. Melatonin stimulates brain glutathione peroxidase activity[J]. Neurochem Int, 1995, 26(5): 497-502.
21	RODRIGUEZ C, MAYO J C, SAINZ R M, et al. Regulation of antioxidant enzymes: a significant role for melatonin[J]. J Pineal Res, 2004, 36(1): 1-9.
22	GALANO A, MEDINA M E, TAN D X, et al. Melatonin and its metabolites as copper chelating agents and their role in inhibiting oxidative stress: a physicochemical analysis[J]. J Pineal Res, 2015, 58(1): 107-116.
23	MILCZAREK R, HALLMANN A, SOKOŁOWSKA E, et al. Melatonin enhances antioxidant action of α-tocopherol and ascorbate against NADPH- and iron-dependent lipid peroxidation in human placental mitochondria[J]. J Pineal Res, 2010, 49(2): 149-155.
24	JIKI Z, LECOUR S, NDUHIRABANDI F. Cardiovascular benefits of dietary melatonin: a myth or a reality?[J]. Front Physiol, 2018, 9: 528.
25	SCHOLTENS R M, VAN MUNSTER B C, VAN KEMPEN M F, et al. Physiological melatonin levels in healthy older people: a systematic review[J]. J Psychosom Res, 2016, 86: 20-27.
26	ACUÑA-CASTROVIEJO D, ESCAMES G, VENEGAS C, et al. Extrapineal melatonin: sources, regulation, and potential functions[J]. Cell Mol Life Sci, 2014, 71(16): 2997-3025.
27	SALUSTIANO E M A, DE PINHO J C, PROVOST K, et al. Maternal serum hormonal factors in the pathogenesis of preeclampsia[J]. Obstet Gynecol Surv, 2013, 68(2): 141-150.
28	KIVELÄ A, KAUPPILA A, LEPPÄLUOTO J, et al. Serum and amniotic fluid melatonin during human labor[J]. J Clin Endocrinol Metab, 1989, 69(5): 1065-1068.
29	NAKAMURA Y, TAMURA H, KASHIDA S, et al. Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy[J]. J Pineal Res, 2001, 30(1): 29-33.
30	SHIMADA M, SEKI H, SAMEJIMA M, et al. Salivary melatonin levels and sleep-wake rhythms in pregnant women with hypertensive and glucose metabolic disorders: a prospective analysis[J]. Biosci Trends, 2016, 10(1): 34-41.
31	VALIAS G R, GOMES P R L, AMARAL F G, et al. Urinary angiotensinogen-melatonin ratio in gestational diabetes and preeclampsia[J]. Front Mol Biosci, 2022, 9: 800638.
32	ZENG K, GAO Y, WAN J, et al. The reduction in circulating levels of melatonin may be associated with the development of preeclampsia[J]. J Hum Hypertens, 2016, 30(11): 666-671.
33	TRANQUILLI A L, TURI A, GIANNUBILO S R, et al. Circadian melatonin concentration rhythm is lost in pregnant women with altered blood pressure rhythm[J]. Gynecol Endocrinol, 2004, 18(3): 124-129.
34	BOUCHLARIOTOU S, LIAKOPOULOS V, GIANNOPOULOU M, et al. Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm[J]. Ren Fail, 2014, 36(7): 1001-1007.
35	YAMAMOTO D DE R, YAMAMOTO L DE R, ROCHA L P, et al. Increase of placental sensitivity to melatonin and the alteration to its local synthesis in hypertensive syndromes in pregnancy[J]. Hypertens Pregnancy, 2013, 32(2): 120-128.
36	TOMAS S Z, PRUSAC I K, ROJE D, et al. Trophoblast apoptosis in placentas from pregnancies complicated by preeclampsia[J]. Gynecol Obstet Investig, 2011, 71(4): 250-255.
37	KARUMANCHI S A, GRANGER J P. Preeclampsia and pregnancy-related hypertensive disorders[J]. Hypertension, 2016, 67(2): 238-242.
38	WAKATSUKI A, OKATANI Y. Melatonin protects against the free radical-induced impairment of nitric oxide production in the human umbilical artery[J]. J Pineal Res, 2000, 28(3): 172-178.
39	WAKATSUKI A, OKATANI Y, IKENOUE N, et al. Melatonin protects against oxidized low-density lipoprotein-induced inhibition of nitric oxide production in human umbilical artery[J]. J Pineal Res, 2001, 31(3): 281-288.
40	ZHAO M, LI Y, XU L, et al. Melatonin prevents preeclamptic sera and antiphospholipid antibodies inducing the production of reactive nitrogen species and extrusion of toxic trophoblastic debris from first trimester placentae[J]. Placenta, 2017, 58: 17-24.
41	OKATANI Y, WAKATSUKI A, SHINOHARA K, et al. Melatonin stimulates glutathione peroxidase activity in human chorion[J]. J Pineal Res, 2001, 30(4): 199-205.
42	HANNAN N J, BINDER N K, BEARD S, et al. Melatonin enhances antioxidant molecules in the placenta, reduces secretion of soluble fms-like tyrosine kinase 1 (sFlt) from primary trophoblast but does not rescue endothelial dysfunction: an evaluation of its potential to treat preeclampsia[J]. PLoS One, 2018, 13(4): e0187082.
43	HOBSON S R, GURUSINGHE S, LIM R, et al. Melatonin improves endothelial function in vitro and prolongs pregnancy in women with early-onset preeclampsia[J]. J Pineal Res, 2018, 65(3): e12508.
44	ZUO J, JIANG Z. Melatonin attenuates hypertension and oxidative stress in a rat model of L-NAME-induced gestational hypertension[J]. Vasc Med, 2020, 25(4): 295-301.
45	UZUN M, GENCER M, TURKON H, et al. Effects of melatonin on blood pressure, oxidative stress and placental expressions of TNFα, IL-6, VEGF and sFlt-1 in RUPP rat model of preeclampsia[J]. Arch Med Res, 2017, 48(7): 592-598.
46	OKATANI Y, WAKATSUKI A, SHINOHARA K, et al. Melatonin protects against oxidative mitochondrial damage induced in rat placenta by ischemia and reperfusion[J]. J Pineal Res, 2001, 31(2): 173-178.
47	LANOIX D, LACASSE A A, REITER R J, et al. Melatonin: the watchdog of villous trophoblast homeostasis against hypoxia/reoxygenation-induced oxidative stress and apoptosis[J]. Mol Cell Endocrinol, 2013, 381(1/2): 35-45.
48	CHUFFA L G A, LUPI L A, CUCIELO M S, et al. Melatonin promotes uterine and placental health: potential molecular mechanisms[J]. Int J Mol Sci, 2019, 21(1): 300.
49	FU G, YE G, NADEEM L, et al. MicroRNA-376c impairs transforming growth factor-β and nodal signaling to promote trophoblast cell proliferation and invasion[J]. Hypertension, 2013, 61(4): 864-872.
50	LUCAS S F, HÉLÈNE C, LAETITIA L, et al. Human primary trophoblast cell culture model to study the protective effects of melatonin against hypoxia/reoxygenation-induced disruption[J]. J Vis Exp Jove, 2016(113): 54228-54228.
51	SAGRILLO-FAGUNDES L, ASSUNÇÃO SALUSTIANO E M, RUANO R, et al. Melatonin modulates autophagy and inflammation protecting human placental trophoblast from hypoxia/reoxygenation[J]. J Pineal Res, 2018, 65(4): e12520.
52	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.
53	TANG Y, GROOM K, CHAMLEY L, et al. Melatonin, a potential therapeutic agent for preeclampsia, reduces the extrusion of toxic extracellular vesicles from preeclamptic placentae[J]. Cells, 2021, 10(8): 1904.
54	LIU Z, CHEN B, CHANG J, et al. Melatonin regulates trophoblast pyroptosis, invasion and migration in preeclampsia by inhibiting HtrA1 transcription through the microRNA-520c-3p/SETD7 axis[J]. Am J Reprod Immunol, 2022, 87(4): e13523.
55	SUN Y, WANG C, ZHANG N, et al. Melatonin ameliorates hypertension in hypertensive pregnant mice and suppresses the hypertension-induced decrease in Ca²⁺-activated K⁺ channels in uterine arteries[J]. Hypertens Res, 2021, 44(9): 1079-1086.

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褪黑素与妊娠期高血压疾病的关系研究进展

Research progress on the association between melatonin and hypertensive disorder complicating pregnancy

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