子痫前期的中药临床应用与现代药理学进展

doi:10.12280/gjfckx.20240382

摘要/Abstract

摘要：

子痫前期是一种妊娠特异性疾病，临床以妊娠20周后出现高血压、蛋白尿等症状为主要特征，子痫前期严重危害母婴生命健康，是导致孕产妇和围产儿死亡率增高的重要因素之一。近年来，采用中药汤剂、活血化瘀类中药注射液等治疗子痫前期的研究增多，取得了良好的临床疗效。现代药理学研究发现，葛根素、天麻素、钩藤碱、人参皂苷、白术内酯、丹参素、川芎嗪、黄芪甲苷等成分能够促进滋养细胞增殖和侵袭，改善实验动物妊娠过程，对子痫前期的治疗起到积极作用。梳理相关文献，通过结合临床疗效与机制研究，分析中药临床用药合理性，为中药防治子痫前期的临床应用与开发提供参考。

关键词: 先兆子痫, 滋养细胞, 治疗结果, 中药, 药理学

Abstract:

Preeclampsia is a pregnancy-related disease clinically characterized by high blood pressure and proteinuria after 20 weeks of gestation. Preeclampsia is a serious danger to the life and health of mothers and infants, and is one of the main causes of maternal and perinatal mortality. For the past few years, multiple Chinese herbal formulas and Chinese medicine injections have been shown to prevent and treat preeclampsia, and good clinical efficacy has been achieved. Modern pharmacological studies have found that Puerarin, Gastrodin, Rhynchophylline, Ginsenoside, Atractylenolide, Danshensu, Tetramethylpyrazine, Astragaloside can promote trophoblast proliferation and invasion, improve the process of pregnancy in experimental animals and play a positive role in the treatment of preeclampsia. Through the relevant literature and analysed the rationality of the clinical use of traditional Chinese medicines by combining clinical efficacy and mechanism studies, this research aims to accelerate and promote the clinical application and development of traditional Chinese medicine in the prevention and treatment of preeclampsia.

Key words: Pre-eclampsia, Trophoblastic cell, Treatment outcome, Traditional Chinese drugs, Pharmacology

任毅, 胡玉莲, 王新, 张琦, 刘超, 高慧婕. 子痫前期的中药临床应用与现代药理学进展[J]. 国际妇产科学杂志, 2024, 51(4): 442-447.

REN Yi, HU Yu-lian, WANG Xin, ZHANG Qi, LIU Chao, GAO Hui-jie. Clinical Application and Modern Pharmacological Progress of Traditional Chinese Medicine in Preeclampsia[J]. Journal of International Obstetrics and Gynecology, 2024, 51(4): 442-447.

图/表 1

参考文献 40

[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. doi: 10.3760/cma.j.cn112141-20200114-00039.
[2]	Phipps EA, Thadhani R, Benzing T, et al. Pre-eclampsia: pathogenesis, novel diagnostics and therapies[J]. Nat Rev Nephrol, 2019, 15(5):275-289. doi: 10.1038/s41581-019-0119-6. pmid: 30792480
[3]	Cindrova-Davies T, Sferruzzi-Perri AN. Human placental development and function[J]. Semin Cell Dev Biol, 2022, 131:66-77. doi: 10.1016/j.semcdb.2022.03.039. pmid: 35393235
[4]	梁结明, 刘国成. 子痫前期发病机制的研究进展[J]. 国际妇产科学杂志, 2023, 50(4):405-408,420. doi: 10.12280/gjfckx.20230106.
[5]	Stepan H, Galindo A, Hund M, et al. Clinical utility of sFlt-1 and PlGF in screening, prediction, diagnosis and monitoring of pre-eclampsia and fetal growth restriction[J]. Ultrasound Obstet Gynecol, 2023, 61(2):168-180. doi: 10.1002/uog.26032.
[6]	Liang X, Liu Y, Chen L, et al. The natural compound puerarin alleviates inflammation and apoptosis in experimental cell and rat preeclampsia models[J]. Int Immunopharmacol, 2021,99:108001. doi: 10.1016/j.intimp.2021.108001.
[7]	He L, Wu X, Zhang X, et al. Puerarin protects against H₂O₂-induced apoptosis of HTR-8/SVneo cells by regulating the miR-20a-5p/VEGFA/Akt axis[J]. Placenta, 2022, 126:202-208. doi: 10.1016/j.placenta.2022.06.015.
[8]	Guo J, Bian W, Jiang H. Puerarin attenuates preeclampsia-induced trophoblast mobility loss and inflammation by modulating miR-181b-5p/RBAK axis[J]. Am J Reprod Immunol, 2022, 87(2):e13510. doi: 10.1111/aji.13510.
[9]	何英姿, 黄承飞. 葛根素对妊娠高血压模型大鼠血管活性物质及胎盘组织的影响[J]. 中国临床药理学杂志, 2020, 36(14):2042-2044. doi: 10.13699/j.cnki.1001-6821.2020.14.036.
[10]	王锋, 徐静, 刘晴, 等. 基于Gadd45α-p38MAPK通路研究葛根素对子痫前期大鼠胎盘氧化应激的影响及作用机制[J]. 中国现代应用药学, 2022, 39(16):2090-2095. doi: 10.13748/j.cnki.issn1007-7693.2022.16.007.
[11]	Lv J, Shi S, Zhang B, et al. Role of puerarin in pathological cardiac remodeling: A review[J]. Pharmacol Res, 2022,178:106152. doi: 10.1016/j.phrs.2022.106152.
[12]	Xiao G, Tang R, Yang N, et al. Review on pharmacological effects of gastrodin[J]. Arch Pharm Res, 2023, 46(9/10):744-770. doi: 10.1007/s12272-023-01463-0.
[13]	Mei Z, Huang B, Qian X, et al. Gastrodin improves preeclampsia-induced cell apoptosis by regulation of TLR4/NF-κB in rats[J]. Food Sci Nutr, 2020, 8(2):820-829. doi: 10.1002/fsn3.1342. pmid: 32148791
[14]	肖艳平, 付久园, 王晓华, 等. 钩藤碱对人绒毛膜滋养层细胞增殖、迁移和侵袭的影响[J]. 中成药, 2022, 44(5):1621-1625. doi: 10.3969/j.issn.1001-1528.2022.05.046.
[15]	Yang Q, Zheng M, Yan J, et al. Rhynchophylline improves trophocyte mobility potential by upregulating ZEB1 level via the inhibition of miR-141-3p level[J]. Biosci Biotechnol Biochem, 2021, 85(2):280-286. doi: 10.1093/bbb/zbaa016.
[16]	Geetha RG, Ramachandran S. Recent Advances in the Anti-Inflammatory Activity of Plant-Derived Alkaloid Rhynchophylline in Neurological and Cardiovascular Diseases[J]. Pharmaceutics, 2021, 13(8):1170. doi: 10.3390/pharmaceutics13081170.
[17]	Jin M, Cao B, Lin C, et al. Tianma Gouteng Decoction Exerts Pregnancy-Protective Effects Against Preeclampsia via Regulation of Oxidative Stress and NO Signaling[J]. Front Pharmacol, 2022,13:849074. doi: 10.3389/fphar.2022.849074.
[18]	周伟弢, 季红薇, 赵楚楚, 等. 畲药山腊梅叶联合天麻钩藤饮通过调控TLR4/NF-KB信号通路预防早发型子痫前期的效果及其机制研究[J]. 中国妇幼保健, 2023, 38(23):4679-4684. doi: 10.19829/j.zgfybj.issn.1001-4411.2023.23.038.
[19]	Cai L, Hu F, Fu W, et al. Ginsenoside Rg2 Ameliorates Brain Injury After Intracerebral Hemorrhage in a Rat Model of Preeclampsia[J]. Reprod Sci, 2021, 28(12):3431-3439. doi: 10.1007/s43032-021-00692-2. pmid: 34270001
[20]	宋姗姗, 杨洋, 何静, 等. 人参皂苷Rg1对子痫前期大鼠氧化应激和炎症的调控作用及机制研究[J]. 中国临床药理学与治疗学, 2020, 25(10):1088-1096. doi: 10.12092/j.issn.1009-2501.2020.10.002.
[21]	Shaukat A, Shaukat I, Rajput SA, et al. Ginsenoside Rb1 Mitigates Escherichia coli Lipopolysaccharide-Induced Endometritis through TLR4-Mediated NF-κB Pathway[J]. Molecules, 2021, 26(23):7089. doi: 10.3390/molecules26237089.
[22]	Liu M, Wang RB, Xing JH, et al. Atractylenolide inhibits apoptosis and oxidative stress of HTR-8/SVneo cells by activating MAPK/ERK signalling in preeclampsia[J]. Phytomedicine, 2021,93:153773. doi: 10.1016/j.phymed.2021.153773.
[23]	Ives CW, Sinkey R, Rajapreyar I, et al. Preeclampsia-Pathophysiology and Clinical Presentations: JACC State-of-the-Art Review[J]. J Am Coll Cardiol, 2020, 76(14):1690-1702. doi: 10.1016/j.jacc.2020.08.014. pmid: 33004135
[24]	Rolnik DL, Nicolaides KH, Poon LC. Prevention of preeclampsia with aspirin[J]. Am J Obstet Gynecol, 2022, 226(2S):S1108-S1119. doi: 10.1016/j.ajog.2020.08.045.
[25]	Kong J, Li S, Li Y, et al. Effects of Salvia miltiorrhiza active compounds on placenta-mediated pregnancy complications[J]. Front Cell Dev Biol, 2023,11:1034455. doi: 10.3389/fcell.2023.1034455.
[26]	唐帅, 李阳, 黄飞跃, 等. 基于Wnt/β-catenin信号通路探究丹参素减轻滋养细胞氧化应激反应的机制[J]. 中国实验诊断学, 2023, 27(12):1458-1463. doi: 10.3969/j.issn.1007-4287.2023.12.017.
[27]	Zhiqiang Z, Chong Z, Yunxia Z. Salvianolic acid B promotes the invasion and migration of HO-induced HTR-8/Svneo trophoblast cells by upregulating matrix metalloproteinase-9 the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B pathway[J]. J Tradit Chin Med, 2023, 43(3):457-465. doi: 10.19852/j.cnki.jtcm.20220707.005.
[28]	康宁, 张清燕, 刘真, 等. 丹参水溶性成分拮抗脂多糖诱导HTR8/SVneo滋养层细胞凋亡的作用机制[J]. 中国现代应用药学, 2023, 40(11):1454-1460. doi: 10.13748/j.cnki.issn1007-7693.20230084.
[29]	彭琼琳, 黄敏. 复方丹参注射液对子痫前期大鼠凝血功能和肾功能的影响研究[J]. 现代医药卫生, 2021, 37(23):3989-3992. doi: 10.3969/j.issn.1009-5519.2021.23.007.
[30]	Gu S, Shen H, Zhou Y, et al. Tetramethylpyrazine reduces the consequences of nitric oxide inhibition in pregnant rats[J]. J Cell Physiol, 2019, 234(11):19799-19806. doi: 10.1002/jcp.28579. pmid: 30937928
[31]	Wang M, Zhang L, Huang X, et al. Ligustrazine promotes hypoxia/reoxygenation-treated trophoblast cell proliferation and migration by regulating the microRNA-27a-3p/ATF3 axis[J]. Arch Biochem Biophys, 2023,737:109522. doi: 10.1016/j.abb.2023.109522.
[32]	Wang FG, Liu M, Lin P, et al. Astragaloside Ⅳ protects human trophoblast HTR8/SVneo cells from H₂O₂-Induced oxidative stress via Nrf2-Keap1-p62 feedback loop[J]. J Funct Foods, 2021,85:104621. doi: 10.1016/j.jff.2021.104621.
[33]	Tuerxun D, Aierken R, Zhang YM, et al. Astragaloside Ⅳ alleviates lipopolysaccharide-induced preeclampsia-like phenotypes via suppressing the inflammatory responses[J]. Kaohsiung J Med Sci, 2021, 37(3):236-244. doi: 10.1002/kjm2.12313.
[34]	Zhao L, Xiong M, Liu Y. Baicalin enhances the proliferation and invasion of trophoblasts and suppresses vascular endothelial damage by modulating long non-coding RNA NEAT1/miRNA-205-5p in hypertensive disorder complicating pregnancy[J]. J Obstet Gynaecol Res, 2021, 47(9):3060-3070. doi: 10.1111/jog.14789.
[35]	李亚梅, 王燕侠. 黄芩苷激活胆碱能抗炎途径改善脂多糖诱发的子痫前期大鼠症状[J]. 中国免疫学杂志, 2020, 36(21):2587-2591. doi: 10.3969/j.issn.1000-484X.2020.21.006.
[36]	Szulc M, Kujawski R, Mikołajczak PŁ, et al. Combined Effects of Methyldopa and Baicalein or Scutellaria baicalensis Roots Extract on Blood Pressure, Heart Rate, and Expression of Inflammatory and Vascular Disease-Related Factors in Spontaneously Hypertensive Pregnant Rats[J]. Pharmaceuticals(Basel), 2022, 15(11):1342. doi: 10.3390/ph15111342.
[37]	Baradaran Rahimi V, Askari VR, Hosseinzadeh H. Promising influences of Scutellaria baicalensis and its two active constituents, baicalin, and baicalein, against metabolic syndrome: A review[J]. Phytother Res, 2021, 35(7):3558-3574. doi: 10.1002/ptr.7046. pmid: 33590943
[38]	Wang J, Zhang Y, Che D, et al. Baicalin induces Mrgprb2-dependent pseudo-allergy in mice[J]. Immunol Lett, 2020, 226:55-61. doi: 10.1016/j.imlet.2020.07.006. pmid: 32707128
[39]	付永会, 高继, 何蒙会, 等. 当归多糖对子痫前期大鼠胎盘灌注的影响及机制研究[J]. 中药药理与临床, 2022, 38(3):91-95. doi: 10.13412/j.cnki.zyyl.2022.03.008.
[40]	刘琳, 柴志勇, 刁云辉, 等. 当归多糖对氧化型低密度脂蛋白诱导的血管内皮细胞损伤的保护作用研究[J]. 中国临床药理学杂志, 2020, 36(7):818-821.

方剂/中成药/注射液	相似方剂（成分）	文献报道（近10年）	适用诊断	疗效评价（对比对照组患者）
葛根汤	黄芪党参葛根汤	5篇	PE；ESPE；妊娠期高血压	尿蛋白、动脉压、脐动脉血流阻力降低显著，孕周延长，抑制氧化应激
天麻钩藤饮	天麻钩藤饮加减；天麻钩藤饮加味；半夏白术天麻汤	9篇	PE；SPE；ESPE；妊娠期高血压	降血压、降尿蛋白效果显著，症状改善，内皮功能恢复明显，凝血功能改善，肾功能恢复明显
四君子汤	黄芪四君子汤	5篇	妊娠期高血压	治疗总有效率高，预后良好
丹参滴丸	复方丹参滴丸	5篇	PE；SPE；ESPE	降低凝血程度，改善妊娠结局
丹参注射液	复方丹参注射液；香丹注射液	105篇	PE；SPE；ESPE；妊娠期高血压	降血压，调节微循环，改善凝血功能，减少并发症，降低妊娠不良结局发生率，胎龄延长，新生儿死亡率降低，产后出血减少
川芎嗪注射液	无	10篇	PE；SPE；ESPE；妊娠期高血压	降血压，并发症发生率及新生儿死亡率显著降低
丹参川芎嗪注射液	丹参注射液联合川芎嗪注射液	5篇	PE；SPE；ESPE	降血压，抑制炎症及氧化损伤，保护血管内皮功能，症状减轻，妊娠结局改善
黄芪注射液	无	3篇	PE	凝血功能改善，产后出血减少

方剂/中成药/注射液	相似方剂（成分）	文献报道（近10年）	适用诊断	疗效评价（对比对照组患者）
葛根汤	黄芪党参葛根汤	5篇	PE；ESPE；妊娠期高血压	尿蛋白、动脉压、脐动脉血流阻力降低显著，孕周延长，抑制氧化应激
天麻钩藤饮	天麻钩藤饮加减；天麻钩藤饮加味；半夏白术天麻汤	9篇	PE；SPE；ESPE；妊娠期高血压	降血压、降尿蛋白效果显著，症状改善，内皮功能恢复明显，凝血功能改善，肾功能恢复明显
四君子汤	黄芪四君子汤	5篇	妊娠期高血压	治疗总有效率高，预后良好
丹参滴丸	复方丹参滴丸	5篇	PE；SPE；ESPE	降低凝血程度，改善妊娠结局
丹参注射液	复方丹参注射液；香丹注射液	105篇	PE；SPE；ESPE；妊娠期高血压	降血压，调节微循环，改善凝血功能，减少并发症，降低妊娠不良结局发生率，胎龄延长，新生儿死亡率降低，产后出血减少
川芎嗪注射液	无	10篇	PE；SPE；ESPE；妊娠期高血压	降血压，并发症发生率及新生儿死亡率显著降低
丹参川芎嗪注射液	丹参注射液联合川芎嗪注射液	5篇	PE；SPE；ESPE	降血压，抑制炎症及氧化损伤，保护血管内皮功能，症状减轻，妊娠结局改善
黄芪注射液	无	3篇	PE	凝血功能改善，产后出血减少