[1]陈 西,罗 岚,宁东红,等.胶艾汤对模拟特发性流产的线粒体调控作用机制[J].陕西中医,2025,46(1):31-37.[doi:DOI:10.3969/j.issn.1000-7369.2025.01.006]
　CHEN Xi,LUO Lan,NING Donghong,et al.The mechanism of mitochondrial regulation by Jiao Ai decoction in a model of idiopathic miscarriage[J].,2025,46(1):31-37.[doi:DOI:10.3969/j.issn.1000-7369.2025.01.006]
点击复制

胶艾汤对模拟特发性流产的线粒体调控作用机制
分享到：

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
46
期数:
2025年1期
页码:
31-37
栏目:
基础研究
出版日期:
2025-01-05

文章信息/Info

Title:
The mechanism of mitochondrial regulation by Jiao Ai decoction in a model of idiopathic miscarriage
作者:
陈 西; 罗 岚; 宁东红; 谢春红; 彭艳丽; 梁 煦
(湖南省妇幼保健院中医妇科,湖南 长沙 410000)
Author(s):
CHEN Xi; LUO Lan; NING Donghong; XIE Chunhong; PENG Yanli; LIANG Xu
(Department of Traditional Chinese Medicine Gynecology,Hunan Maternal and Child Health Hospital,Changsha 410000,China)
关键词:
自然流产;  胶艾汤;  miR-29α-3p;  线粒体;  凋亡;  滋养层细胞
Keywords:
Spontaneous abortion;  Jiao Ai decoction;  miR-29α-3p;  Mitochondrial;  Apoptosis;  Trophoblast cell
分类号:
R 714.21
DOI:
DOI:10.3969/j.issn.1000-7369.2025.01.006
文献标志码:
A
摘要:
目的:探究胶艾汤对模拟特发性流产的线粒体调控作用机制。方法:细胞实验设置对照组、胶艾汤组、miR-29α-3p模拟物组、胶艾汤+miR-29α-3p模拟物组,对人绒毛膜滋养层细胞HTR-8/SVneo进行培养和处理,检测miR-29α-3p表达、线粒体凋亡、细胞色素C释放、凋亡相关蛋白表达、细胞迁移和侵袭能力。动物实验选用怀孕的C57BL/6J小鼠建立流产模型,分组进行胶艾汤灌胃治疗和miR-29α-3p模拟物腹腔注射治疗,观察流产情况、胎盘组织学变化、miR-29α-3p表达、线粒体凋亡相关指标。结果:细胞实验中,与对照组相比,胶艾汤组里miR-29α-3p的表达水平于48 h明显提升(P<0.001),miR-29α-3p模拟物组的表达水平也显著高于对照组,而胶艾汤+miR-29α-3p模拟物组的表达水平最高。胶艾汤和miR-29α-3p模拟物能够降低线粒体膜电位变化,减少细胞色素C的释放,调节凋亡相关蛋白(Bax表达降低,Bcl-2表达升高,Caspase-3活性降低)的表达,使其向抗凋亡方向转变,从而抑制线粒体凋亡,联合使用时效果更优。胶艾汤和miR-29α-3p模拟物还能够促进细胞的迁移和侵袭能力,联合使用时效果更为显著。动物实验中,流产模型组的流产率较高,为(31.17±0.67)%; 胶艾汤治疗组的流产率降低至(13.30±0.36)%; 胶艾汤+miR-29α-3p模拟物组的流产率进一步降低至(5.77±0.36)%(P<0.001)。胶艾汤治疗组胎盘组织的形态和结构得到改善,滋养层细胞的损伤减轻; 胶艾汤+miR-29α-3p模拟物组胎盘组织的损伤程度更轻,滋养层细胞形态基本正常。胶艾汤治疗组与胶艾汤+miR-29α-3p模拟物组在胎盘组织中miR-29α-3p的表达水平提升,而且胶艾汤+miR-29α-3p模拟物组的表达水平更高。胶艾汤治疗组和胶艾汤+miR-29α-3p模拟物组胎盘组织中Bax表达降低(P<0.01),Bcl-2表达升高(P<0.001),Caspase-3活性降低(P<0.01)。结论:胶艾汤能够上调miR-29α-3p的表达,调控线粒体凋亡,干预滋养层细胞侵袭迁移,降低流产发生风险,miR-29α-3p在其中发挥重要作用。
Abstract:
Objective:To explore the mechanism of mitochondrial regulation by Jiao Ai decoction in a model of idiopathic miscarriage. Methods:Cell experiments and animal experiments were conducted.In the cell experiment,the control group,the Jiao Ai decoction group,the miR-29α-3p mimic group,and the Jiao Ai decoction+miR-29α-3p mimic group were set up.Human chorionic trophoblast cells HTR-8/SVneo were cultured and treated,and the expression of miR-29α-3p,mitochondrial apoptosis,cytochrome C release,apoptosis-related protein expression,cell migration and invasion ability were detected.In the animal experiment,pregnant C57BL/6J mice were selected to establish a miscarriage model,and the groups were treated with Jiao Ai decoction by gavage and miR-29α-3p mimic by intraperitoneal injection.The miscarriage situation,placental histology changes,miR-29α-3p expression,mitochondrial apoptosis-related indicators,and oxidative stress indicators were observed.Results:In the cell experiment,compared with the control group,the expression level of miR-29α-3p in the Jiao Ai decoction group was significantly increased at 48 hours(P<0.001),the expression level in the miR-29α-3p mimic group was also significantly higher than that in the control group,and the expression level in the Jiao Ai decoction+miR-29α-3p mimic group was the highest.Jiao Ai decoction and miR-29α-3p mimic could reduce the change of mitochondrial membrane potential,reduce the release of cytochrome C,regulate the expression of apoptosis-related proteins(Bax expression decreased,Bcl-2 expression increased,Caspase-3 activity decreased),and make them shift to the anti-apoptotic direction,thereby inhibiting mitochondrial apoptosis,and the combined use had a better effect.Jiao Ai decoction and miR-29α-3p mimic could also promote the migration and invasion ability of cells,and the combined use had a more significant effect.In the animal experiment,the miscarriage rate in the miscarriage model group was higher,at(31.17±0.67)%.The miscarriage rate in the Jiao Ai decoction treatment group was reduced to(13.30±0.36)%.The miscarriage rate in the Jiao Ai decoction+miR-29α-3p mimic group was further reduced to(5.77±0.36)%(P<0.001).The morphology and structure of placental tissue in the Jiao Ai decoction treatment group were improved,and the damage of trophoblast cells was reduced.The degree of damage to placental tissue in the Jiao Ai decoction+miR-29α-3p mimic group was lighter,and the morphology of trophoblast cells was basically normal.The expression level of miR-29α-3p in placental tissue was increased in the Jiao Ai decoction treatment group and the Jiao Ai decoction+miR-29α-3p mimic group,and the expression level in the Jiao Ai decoction+miR-29α-3p mimic group was higher.In the placental tissue of the Jiao Ai decoction treatment group and the Jiao Ai Decoction+miR-29α-3p mimic group,Bax expression was decreased(P<0.01),Bcl-2 expression was increased(P<0.001),and Caspase-3 activity was decreased(P<0.01).In the placental tissue of the Jiao Ai decoction treatment group and the Jiao Ai decoction+miR-29α-3p mimic group,SOD activity was increased,MDA content was decreased,and the improvement effect of the Jiao Ai decoction+miR-29α-3p mimic group was better(P<0.001).Conclusion:Jiao Ai decoction can up-regulate the expression of miR-29α-3p,regulate mitochondrial apoptosis,intervene in the invasion and migration of trophoblast cells,and reduce the risk of miscarriage.miR-29α-3p plays an important role in it.

参考文献/References:

[1] CASTELLANOS GUTIERREZ A S,FIGUERAS F,MORALES-PRIETO D M,et al.Placental damage in pregnancies with systemic lupus erythematosus:A narrative review[J].Frontiers in Immunology,2022,13:941586.
[2] 窦娜,刘筱茂,张媛,等.胎宝汤治疗黄体功能不全型先兆流产疗效研究[J].陕西中医,2024,45(9):1222-1225.
[3] DROZDZIK M,SZLARB N,KURZAWSKI M.Interleukin-6 level and gene polymorphism in spontaneous miscarriage[J].Tissue Antigens,2013,82(3):171-176.
[4] CHEN X,GUO D Y,YIN T L,et al.Non-coding RNAs regulate placental trophoblast function and participate in recurrent abortion[J].Frontiers in Pharmacology,2021,12:646521.
[5] WANG M,ZHENG L,MA S,et al.Biogenesis and function of exosome lncRNAs and their role in female pathological pregnancy[J].Frontiers in Endocrinology,2023,14:1191721.
[6] 李春华,司津歌,曹伍兰.MiRNA-21-5p靶向调节SATB1参与妊娠滋养层细胞的增殖和迁移作用的研究[J].中国妇产科临床杂志,2024,25(5):433-437.
[7] 徐霞,王鹏程,韩璐.微小miR-184在调控女性滋养层细胞凋亡中的作用及其分子机制探究[J].陕西医学杂志,2023,52(10):1431-1433,1441.
[8] HARRIS L K.VIP:The big shot peptide in pregnancy and beyond?[J].Acta Physiologica,2021,232(1):256-259.
[9] SCHATZ F,PAPP C,TOTH-PAL E,et al.In vitro regulation of stromelysin-1 in human endometrial stromal cells[J].Annals of the New York Academy of Sciences,1994,732(1):479-481.
[10] WANG J,DING J,ZHANG S,et al.Decreased USP2a expression inhibits trophoblast invasion and associates with recurrent miscarriage[J].Frontiers in Immunology,2021,12:717370.
[11] CHEN Z Y,LI Z,ZONG Y,et al.Exosome-delivered miR-410-3p reverses epithelial-mesenchymal transition,migration and invasion of trophoblasts in spontaneous abortion[J].Journal of Cellular and Molecular Medicine,2024,28(3):e18097.
[12] GUO J,ZHAO J,TIAN P,et al.BaP/BPDE exposure causes human trophoblast cell dysfunctions and induces miscarriage by up-regulating lnc-HZ06-regulated IL-1β[J].Journal of Hazardous Materials,2024:134741.
[13] HAN H,HU S,HU Y,et al.Mitophagy in ototoxicity[J].Frontiers in Cellular Neuroscience,2023,17:1140916.
[14] JIN F,QIAO C,LUAN N,et al.Lentivirus-mediated PHLDA2 overexpression inhibits trophoblast proliferation,migration and invasion,and induces apoptosis[J].International Journal Of Molecular Medicine,2016,37(4):949-957.
[15] XU Y Y,LIU Y,CUI L,et al.Hypoxic effects on the mitochondrial content and functions of the placenta in fetal growth restriction[J].Placenta,2021,114:100-107.
[16] HU J,WANG H,JIANG R,et al.Effects of indented zona pellucida on oocyte growth and development explored from changes of gene expression in cumulus cells[J].Archives of Gynecology and Obstetrics,2023,308(3):1023-1033.
[17] SHANG J,WANG Q,WANG J,et al.miR-708-3p promotes gastric cancer progression through downregulating ETNK1[J].Heliyon,2023,9(9):494-499.
[18] CHENG M H,KUO H F,CHANG C Y,et al.Curcumin regulates pulmonary extracellular matrix remodeling and mitochondrial function to attenuate pulmonary fibrosis by regulating the miR-29α-3p/DNMT3A axis[J].Biomedicine & Pharmacotherapy,2024,174:116572.
[19] 程敏.胶艾汤方论研究[D].昆明:云南中医药大学,2023.
[20] ZHANG M,GENG T,JING S H,et al.Chemical profile and miscarriage prevention evaluation of Jiao-Ai Decoction,a classical traditional Chinese formula[J].Journal of Pharmaceutical and Biomedical Analysis,2022,217:114832.
[21] 潘爱珍,陈珂,林玉洁.胶艾汤在妇科临床应用举隅[J].内蒙古中医药,2023,42(8):100-101.
[22] 关素珍,尹金磊,宗静娟.保孕汤联合黄体酮注射液对先兆流产的临床研究[J].中药药理与临床,2015,31(4):249-251.
[23] 尹鑫,刘文,梁登辉,等.自拟健脾补肾养血安胎汤联合左甲状腺素钠片治疗孕早期先兆流产合并亚临床甲状腺功能减退症疗效观察[J].现代中西医结合杂志,2017,26(17):1900-1902.
[24] 王韫琪,向丽娟,李兆萍.益肾固冲汤联合保胎贴穴位贴敷治疗肾气虚证胎动不安(先兆流产)患者的临床效果[J].世界中医药,2018,13(11):2843-2846.
[25] 王健人.胶艾汤合寿胎丸治疗胎动不安(肾虚血瘀证)32例临床观察[J].江西中医药大学学报,2024,36(2):58-60.

备注/Memo

备注/Memo:
基金项目:湖南省中医药科研计划项目(B2024107)
更新日期/Last Update: 2025-01-09