减味寿胎丸通过抑制Exo-miR-410-3p摄取促进滋养细胞上皮间质转化、迁移及侵袭减少胚胎流产

doi:10.12122/j.issn.1673-4254.2026.09.02

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (9): 2006-2022.doi: 10.12122/j.issn.1673-4254.2026.09.02

• • 上一篇

减味寿胎丸通过抑制Exo-miR-410-3p摄取促进滋养细胞上皮间质转化、迁移及侵袭减少胚胎流产

徐展发¹, 陈贞月²^,³, 谢丽萍⁴, 李馨怡⁵, 秦耿耿¹(), 郜洁⁶()

^1.南方医科大学，南方医院，广东广州 510515
^2.韶关市第一人民医院广东韶关 512099
^3.；广州中医药大学第一临床医学院，广东广州 510405
^4.南方医科大学，麻醉学院，广东广州 510515
^5.南方医科大学，第一临床医学院，广东广州 510515
^6.广州中医药大学第一附属医院，广东广州 510405

收稿日期:2026-03-11 出版日期:2026-09-20 发布日期:2026-09-30
通讯作者: 秦耿耿,郜洁 E-mail:zealotq@smu.edu.cn;gaojie1769@gzucm.edu.cn
作者简介:徐展发、陈贞月共同为第一作者
徐展发、陈贞月共同为第一作者
第一联系人：徐展发，在读硕士研究生，E-mail: 1622990322@qq.com
陈贞月，博士，主治医师，E-mail: zhenyuechen0907@hotmail.com
基金资助:
国家自然科学基金(81774358)

Jianwei Shoutai Pill reduces spontaneous abortion in mice by inhibiting Exo-miR-410-3p uptake and promoting trophoblast epithelial-mesenchymal transition, migration, and invasion

Zhanfa XU¹, Zhenyue CHEN²^,³, Liping XIE⁴, Xinyi LI⁵, Genggeng QIN¹(), Jie GAO⁶()

^1.Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
^2.Shaoguan First People's Hospital, Shaoguan 512099, China
^3.First Clinical Medical College, University of Chinese Medicine, Guangzhou 510405, , China
^4.School of Anesthesiology, Southern Medical University, Guangzhou 510515, China
^5.First Clinical Medical College, Southern Medical University, Guangzhou 510515, China
^6.First Affiliated Hospital, Guangzhou，University of Chinese Medicine, Guangzhou 510405, , China

Received:2026-03-11 Online:2026-09-20 Published:2026-09-30
Contact: Genggeng QIN, Jie GAO E-mail:zealotq@smu.edu.cn;gaojie1769@gzucm.edu.cn
Supported by:
National Nature Science Foundation of China(81774358)

摘要/Abstract

摘要：

目的探讨减味寿胎丸（JSP）对自然流产（SA）的影响，并探究其是否通过抑制滋养细胞摄取外泌体miR-410-3p（Exo-miR-410-3p）并促进上皮间充质转化（EMT）、迁移及侵袭发挥作用。方法通过电穿孔方法将miR-410-3p模拟物装载入牛奶外泌体以制备Exo-miR-410-3p，通过透射电子显微镜、纳米颗粒追踪分析和Western blotting等方法检测Exo-miR-410-3p的表征。制备对照血清或JSP含药血清。分别设置对照组：HTR-8/Svneo正常培养；Exo-miR-410-3p组：HTR-8/Svneo+Exo-miR-410-3p；Exo-miR-410-3p+对照血清组：HTR-8/Svneo+Exo-miR-410-3p+对照血清；Exo-miR-410-3p+JSP含药血清组：HTR-8/Svneo+Exo-miR-410-3p+JSP含药血清。通过RT-qPCR、Western blotting和免疫荧光染色检测相关表达差异。分别通过CCK-8实验、划痕实验和Transwell实验评估HTR-8/Svneo细胞增殖、迁移及侵袭能力。对荧光标记外泌体进行体内和体外成像追踪，并计算孕鼠胚胎吸收率。通过RT-qPCR、Western blotting、原位杂交和免疫组化行表达差异的体内验证。结果划痕实验和Transwell实验显示，与对照组相比，Exo-miR-410-3p组HTR-8/Svneo细胞迁移和侵袭能力减弱（P<0.01），而JSP含药血清可逆转HTR-8/Svneo细胞减弱的迁移和侵袭能力。体内实验证实，JSP含药血清可抑制Exo-miR-410-3p到达母胎界面，与Exo-miR-410-3p组相比，Exo-miR-410-3p+JSP组胚胎吸收率更低（P<0.01）。JSP含药血清降低SA小鼠体内miR-410-3p的水平（P<0.05），同时上调TRAF6的表达。结论 JSP可能通过抑制滋养层细胞摄取Exo-miR-410-3p，促进SA中滋养层细胞EMT、迁移及侵袭，减少胚胎流产。

关键词: 减味寿胎丸, 自然流产, 外泌体miR-410-3p, 上皮-间质转化, p38 MAPK信号通路

Abstract:

Objective To investigate the therapeutic effect of Jianwei Shoutai Pill (JSP) on spontaneous abortion (SA) in mice and explore its therapeutic mechanism. Methods The miR-410-3p mimic was electroporated into milk exosomes to prepare exosomal miR-410-3p (Exo-miR-410-3p), which was characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. CCK-8, scratch wound healing, and Transwell assays were used to test the effects of control and JSP-medicated rat serum on proliferation, migration, and invasion of trophoblast HTR-8/Svneo cells. Female C57BL/6 mice were divided into SA model group, Model+Exo-miR-410-3p group, Model+Exo-miR-410-3p+P group, and Model+Exo-miR-410-3p+JSP group. The fluorescently labeled exosomes was tracked using in vivo and ex vivo imaging and embryo resorption rate was calculated. RT-qPCR, Western blotting, in situ hybridization, and immunohistochemical studies were carried out for further in vivo verification. Results Treatment with Exo-miR-410-3p significantly reduced migration and invasion capacities of HTR-8/Svneo cells, and these inhibitory effects were effectively reversed by JSP intervention. In pregnant C57BL/6 mouse models, JSP treatment prevented Exo-miR-410-3p from reaching the maternal-fetal interface. Consistently, the embryo resorption rate was significantly lower in Exo-miR-410-3p+JSP group than in Exo-miR-410-3p alone group [(20.73±3.77)% vs (74.95±10.09)%, P<0.01]. JSP treatment significant reduced miR-410-3p level and upregulated TRAF6 expression in the female mouse models. Conclusion JSP inhibits Exo-miR-410-3p uptake by trophoblast cells, thereby promoting trophoblast EMT, migration, and invasion and reducing embryo resorption in mouse models of spontaneous abortion.

Key words: Jianwei Shoutai Pill, spontaneous abortion, exosomal miR-410-3p, epithelial-mesenchymal transition, p38 MAPK signaling pathway

徐展发, 陈贞月, 谢丽萍, 李馨怡, 秦耿耿, 郜洁. 减味寿胎丸通过抑制Exo-miR-410-3p摄取促进滋养细胞上皮间质转化、迁移及侵袭减少胚胎流产[J]. 南方医科大学学报, 2026, 46(9): 2006-2022.

Zhanfa XU, Zhenyue CHEN, Liping XIE, Xinyi LI, Genggeng QIN, Jie GAO. Jianwei Shoutai Pill reduces spontaneous abortion in mice by inhibiting Exo-miR-410-3p uptake and promoting trophoblast epithelial-mesenchymal transition, migration, and invasion[J]. Journal of Southern Medical University, 2026, 46(9): 2006-2022.

图/表 15

表1 JSP中3种组成药材的基本信息

Tab.1 Information of 3 constituent herbs in Jianwei Shoutai Pill (JSP)

Chinese name	Botanical^a name	English name	Genus family	Part uesd	Batch number	Weight (g)
Tusizi	Cuscuta chinensis Lam	Cuscutae semen	Convolvulaceae	Seed	150701	20
Sangjisheng	Taxillus sutchuenensis var.duclouxii (Lecomte) H.S.Kiu	Herba taxilli	Loranthaceae	Stem	160601	15
Xuduan	Dipsacus L.	Dipsaci radix	Caprifoliaceae	Stem	140705511	15

图1 JSP冻干粉和JSP含药血清的化学成分和物质基础

Fig.1 Chemoprofile and material basis of JSP lyophilized powder and JSP-medicated rat serum. A: Peak number and chemical characterization of JSP lyophilized powder in negative ion mode. B: Peak number and chemical characterization of JSP lyophilized powder in positive ion mode. C: Peak number and chemical characterization of JSP-containing serum in negative ion mode. D: Peak number and chemical characterization of JSP-containing serum in positive ion mode.

表2 负离子模式下HPLC-MS分析得到的JSP冻干粉末中的10大主要成分

Tab.2 Top 10 ingredients of JSP lyophilized powder by HPLC-MS analysis under negative ion mode

No.	Identification	Formula	RT (min)	[M-H]^-(m/z)			MS2
No.	Identification	Formula	RT (min)	Measured	Predicted	Δ (ppm)	MS2
1	Phloroglucinol	C6H6O3	10.49	127.03892	126.03166	-0.304	109.02865, 99.04446
2	Mussaenosidic acid	C16H24O10	9.32	375.12921	376.13664	1.063	213.07642, 195.06569
3	Apocynin	C9H10O3	7.66	167.07027	166.06299	-0.025	167.07004, 152.04672
4	Methyl cinnamate	C10H10O2	10.91	180.10168	179.09449	-3.573	164.04254, 163.11104
5	6-O-Hexopyranosyl-1-O-[19-hydroxy -28-oxo-3-(pentopyranosyloxy)olean-12-	C47H76O18	16.94	973.5009	974.50825	0.493	928.50079, 927.49738
6	Salicylic acid	C7H6O3	12.96	137.02315	138.03042	-9.200	138.02663, 138.01686
7	Neochlorogenic acid	C16H18O9	8.18	353.08746	354.09470	-1.082	191.05544, 179.03421
8	4,5-Dicaffeoylquinic acid	C25H24O12	12.38	515.11902	516.12623	-1.051	354.09219, 353.08780
9	2-oxopiperidine-3-carbohydrazide	C6H11N3O2	15.25	156.08057	157.08784	-0.557	155.07317, 128.03448
10	Isorhamnetin	C16H12O7	13.65	317.06503	316.05776	-1.729	317.06497, 302.04166

表3 正离子模式下HPLC-MS分析所得JSP冻干粉的10大主要成分

Tab.3 Top 10 ingredients in JSP lyophilized powder by HPLC-MS analysis under positive ion mode

No.	Identification	Formula	RT (min)	[M-H]^-(m/z)			MS2
No.	Identification	Formula	RT (min)	Measured	Predicted	Δ (ppm)	MS2
1	Vanillin	C8H8O3	10.57	153.05446	152.04718	-1.066	136.07547, 135.11678
2	3-hydroxy-3-(2-pyridylmethyl)indolin-2-one	C14H12N2O2	9.59	241.09671	240.08944	-1.834	224.08940, 223.08618
3	Hyperoside	C21H20O12	12.85	465.10165	464.09481	-1.427	304.05289, 303.04953
4	α-Eleostearic acid	C18H30O2	21.85	279.23154	278.22430	-1.021	279.23132, 279.09326
5	Octyl decyl phthalate	C26H42O4	24.28	441.29675	440.28948	-1.272	315.15570, 203.17888
6	Betulin	C30H50O2	23.05	411.36124	410.35400	-1.438	397.26166, 359.24600
7	Maltol	C6H6O3	7.52	127.0390	126.03172	0.244	127.03897, 109.02870
8	6-O-[(2E)-3-(4-Hydroxyphenyl)-2-propenoyl]-1 -O-(3,4,5-trihydroxybenzoyl)hexopyranose	C22H22O12	11.73	477.10422	478.11149	0.961	477.10388, 433.11270
9	Quercetin	C15H10O7	13.57	303.04919	302.04192	-1.854	285.03885, 275.05548
10	Cafestol	C20H28O3	18.92	317.20819	316.20091	-1.739	299.19794, 271.20505

表4 负离子模式下HPLC-M分析得到的含JSP血清10大主要成分

Tab.4 Top 10 ingredients of JSP-medicated rat serum by HPLC-MS analysis under negative ion mode

No.	Identification	Formula	RT(min)	[M-H]^-(m/z)			MS2
No.	Identification	Formula	RT(min)	Measured	Predicted	Δ(ppm)	MS2
1	Linoleic acid	C18H32O2	22.15	325.23828	280.24003	-0.715	279.23294, 59.01225
2	γ-Linolenic acid ethyl ester	C20H34O2	21.68	313.27289	312.26561	-1.761	257.24731, 239.23659
3	1-Stearoylglycerol	C21H42O4	23.04	381.29657	358.30739	-2.560	341.30453, 285.27875
4	(±)11(12)-EET	C20H32O3	19.75	319.22751	320.23479	1.717	301.21756, 257.22751
5	(±)13-HpODE	C18H32O4	19.39	295.22638	294.21925	-0.816	295.22440, 295.18799
6	4-Phenolsulfonic acid	C6H6O4S	10.45	172.99033	173.99760	3.218	93.03314, 79.95588
7	Deoxycholic Acid	C24H40O4	20.02	391.28513	392.29241	-0.648	365.30621, 347.29520
8	Progesterone	C21H30O2	16.98	315.23166	314.22438	-0.665	315.23148, 297.22113
9	4-Methylphenol	C7H8O	13.86	107.04849	108.05577	5.090	67.50848
10	5-trans-Prostaglandin E2	C20 H32O5	17.37	335.22116	334.21403	-2.094	335.22006, 317.21027

表5 正离子模式下HPLC-MS分析所得含JSP血清的10大主要成分

Tab.5 TOP 10 ingredients of JSP-medicated rat serum by HPLC-MS analysis under positive ion mode

No.	Identification	Formula	RT(min)	[M-H]^-(m/z)			MS2
No.	Identification	Formula	RT(min)	Measured	Predicted	Δ(ppm)	MS2
1	Adrenic acid	C22H36O2	23.00	331.26413	332.27136	-0.503	71.01227, 59.00959
2	Hexadecanamide	C16H3NO	21.56	256.26300	255.25574	-1.879	256.26297, 102.09174
3	Palmitoleic acid	C16H30O2	21.91	253.21693	254.22421	-1.453	59.01217, 53.94514
4	11(Z)-Eicosenoic acid	C20H38O2	24.23	309.28006	310.28733	0.489	309.17767, 104.95240
5	DL-Tryptophan	C11H12N2O2	7.28	188.07050	204.08978	-0.469	188.07042, 170.05983
6	Chenodeoxycholic Acid	C24H40O4	19.86	437.29034	438.29762	1.255	409.29636, 391.28537
7	Deoxycholic Acid	C24H40O4	18.52	391.28519	392.29249	-0.648	347.29453, 343.26413
8	Bis(4-ethylbenzylidene)sorbitol	C24H30O6	17.13	415.21078	414.20352	-1.736	135.08035, 119.08560
9	L-Phenylalanine	C9H11NO2	5.27	149.05977	148.05242	-5.921	131.04912, 120.08086
10	3-Methoxyphenylacetic acid	C9H10O3	11.28	165.05475	166.06213	-5.203	165.05470, 165.01831

图2 Exo-Ctrl和Exo-miR-410-3p的表征和鉴定

Fig.2 Characterization and identification of Exo-Ctrl and Exo-miR-410-3p. A: TEM image of milk exosomes (Scale bar=200 nm). B: NTA of the size distribution of milk exosomes. C: Protein levels of CD63, CD81, and TSG101 in milk exosomes measured by Western blotting. D: Expression level of miR-410-3p in Exo-Ctrl or Exo-miR-410-3p measured by RT-qPCR. E: NTA of the size distribution of Exo-Ctrl or Exo-miR-410-3p. F: Fluorescence image of HTR-8/Svneo cells incubated with PKH26-labeled Exo-Ctrl or Exo-miR-410-3p (red) (Scale bar=25 µm). (n=3). ***P<0.001.

图3 Exo-miR-410-3p抑制HTR-8/Svneo细胞EMT、迁移和侵袭

Fig.3 Exo-miR-410-3p suppresses EMT, migration, and invasion of HTR-8/Svneo cells. A: Expression level of miR-410-3p in HTR-8/Svneo cells treated with Exo-Ctrl or Exo-miR-410-3p measured by RT-qPCR. B, C: Protein levels of TRAF6, E-cadherin, N-cadherin, and vimentin in HTR-8/Svneo cells treated with Exo-Ctrl or Exo-miR-410-3p measured by Western blotting and immunofluorescence staining. D, E: Migration and invasion capacities of HTR-8/Svneo cells treated with Exo-Ctrl or Exo-miR-410-3p determined by wound healing and Transwell assays, respectively. Representative images of migrated or invaded cells are shown (Original magnification: ×200). (n=3). **P<0.01, ***P<0.001; ##P<0.01, ###P<0.001.

图4 　JSP 含药血清逆转了Exo-miR-410-3p对HTR-8/Svneo细胞的EMT、迁移和侵袭的抑制作用

Fig.4 　JSP-medicated rat serum reversesinhibitory effects of Exo-miR-410-3p on HTR-8/Svneo cell EMT, migration, and invasion. A:Change of HTR-8/Svneo cell viability treatedwith Exo-miR-410-3p, control or JSPmedicatedserum for 48 h. B: Fluorescenceimage of HTR-8/Svneo cells incubated withPKH26-labeled Exo-miR-410-3p (red) treatedwith control or JSP-medicated serum (scalebar, 25 μm). C, D: Protein levels of TRAF6, Ecadherin,N-cadherin, and Vimentin in HTR-8/Svneo cells treated with control or JSPmedicatedserum under the action of ExomiR-410-3p measured by Western blottingand IF staining. E, F: Migration and invasioncapacities of HTR-8/Svneo cells treated withcontrol or JSP-containing serum under theaction of Exo-miR-410-3p determined bywound healing and Transwell assays,respectively. Representative images ofmigrated or invaded cells are shown (×200).(n=3). *P<0.05,**P<0.01, ***P<0.001, ##P<0.01 ###P<0.001

图5 JSP含药血清对HTR-8/Svneo细胞p38 MAPK信号通路的影响

Fig.5 Effect of JSP-medicated serum on the p38 MAPK signaling pathway in HTR-8/Svneo cells. A, C: Protein levels of p38 and p-p38 in HTR-8/Svneo cells treated with Exo-Ctrl or Exo-miR-410-3p measured by Western blotting and IF staining. B, D: Protein levels of p38 and p-p38 in HTR-8/Svneo cells treated with control or JSP-medicated serum under the action of Exo-miR-410-3p measured by Western blotting and IF staining. (n=3). **P<0.01, ***P<0.001, ##P<0.01, ###P<0.001 vs indicated group.

图6 miR-410-3p/TRAF6/p38 MAPK通路在JSP调控中的核心作用

Fig.6 The core role of the miR-410-3p/TRAF6/p38 MAPK pathway in JSP-mediated regulation. A, B: After transfection with miR-410-3p mimic or inhibitor in HTR-8/Svneo cells, the expression of TRAF6 and p-p38 proteins was detected by Western blotting. C: Effect of knocking down TRAF6 (si TRAF6) or overexpressing TRAF6 (LV TRAF6) on p-p38 protein expression. D: Rescue experiment of co transfection of miR-410-3p mimic and LV TRAF6. E, F: The p38 MAPK signaling pathway inhibitor SB203580 blocks the effects of miR-410-3p inhibitor or LV TRAF6. (n=3). *P<0.05, **P<0.01, ***P<0.001, #P<0.05, ##P<0.01, ###P<0.001.

图7 不同条件下E-cadherin、N-cadherin、Vimentin蛋白的表达情况

Fig.7 Expression of E-cadherin, N-cadherin, and vimentin proteins under different conditions. A: After transfection of miR-410-3p mimic or inhibitor in HTR-8/Svneo cells, the protein expression of E-cadherin, N-cadherin, and vimentin was detected by Western blotting. B: Effect of knocking down TRAF6 (si TRAF6) or overexpressing TRAF6 (LV TRAF6) on the expression of E-cadherin, N-cadherin, and Vimentin proteins. C: Effect of co transfection of miR-410-3p mimic and LV TRAF6 on the expression of E-cadherin, N-cadherin, and vimentin proteins. (n=3). *P<0.05, **P<0.01, ***P<0.001, #P<0.05, ##P<0.01, ###P<0.001.

图8 高剂量的JSP降低雌性小鼠血清、胎盘和子宫中miR-410-3p的水平, 并增加了胎盘中TRAF6的表达

Fig.8 High doses of JSP reduces miR-410-3p in the serum, placenta, and uterus of female mice, but increases TRAF6 expression in the placenta. A-C: Level of miR-410-3p in the serum, placenta, and uterus of female mice treated with low, medium, and high doses of JSP detected by RT-qPCR (n=5). D: Expression level of TRAF6 protein in the placenta of female mice treated with low, medium, and high doses of JSP measured by Western blotting (n=3). *P<0.05, **P<0.01, ***P<0.001.

图9 JSP减少Exo-miR-410-3p诱导的胚胎吸收

Fig.9 JSP can reduce embryo resorption rate induced by Exo-miR-410-3p. A: In vivo fluorescence images of DiR labeled Exo-miR-410-3p in female mice, representative ex vivo fluorescence images in different organs, and the quantification of ex vivo fluorescence images in embryos (n=5). B-D: Expression level of miR-410-3p in the serum, placenta, and uterus of female mice detected by RT-qPCR (n=5). E: Embryo resorption rate of female mice (n=5). F: Expression level of TRAF6 protein in the placenta of female mice measured by Western blotting (n=3). G, H: Distributions of miR-410-3p and TRAF6 in the placenta and uterus of female mice detected by ISH and IHC, respectively (Scale bars=50 μm, 25 μm). *P<0.05, ***P<0.001, #P<0.05, ##P<0.01, ###P<0.001.

图10 JSP通过抑制Exo-miR-410-3p摄取调控滋养细胞EMT、迁移及侵袭减少SA的机制模式图

Fig.10 Schematic diagram illustrating the mechanism by which JSP reduces SA by inhibiting Exo-miR-410-3p uptake to regulate trophoblast EMT, migration, and invasion.

参考文献 65

[1]	Warburton D, Fraser FC. Spontaneous abortion risks in man: data from reproductive histories collected in a medical genetics unit[J]. Am J Human Genetics, 1964, 16(1): 1-25.
[2]	The ESHRE Guideline Group on Rpl, Bender Atik R, Christiansen OB, et al. ESHRE guideline: recurrent pregnancy loss[J]. Hum Reprod Open, 2018, 2018(2): hoy004. doi：10.1093/hropen/hoy004
[3]	Quenby S, Gallos ID, Dhillon-Smith RK, et al. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss[J]. Lancet, 2021, 397(10285): 1658-67. doi：10.1016/s0140-6736(21)00682-6
[4]	Ohno M, Maeda T, Matsunobu A. A cytogenetic study of spontaneous abortions with direct analysis of chorionic villi[J]. Obstet Gynecol, 1991, 77(3): 394-8.
[5]	Skinner J, Luettich K, Ring M, et al. Analysis of fetal DNA in the maternal venous blood for abnormalities of chromosomes 13, 16, 18 and 21 in first-trimester spontaneous miscarriage[J]. J Obstet Gynaecol, 2003, 23(3): 228-32. doi：10.1080/0144361031000098307
[6]	van den Berg MMJ, van Maarle MC, van Wely M, et al. Genetics of early miscarriage[J]. Biochim Biophys Acta BBA Mol Basis Dis, 2012, 1822(12): 1951-9. doi：10.1016/j.bbadis.2012.07.001
[7]	Sierra S, Stephenson M. Genetics of recurrent pregnancy loss[J]. Semin Reprod Med, 2006, 24(1): 17-24. doi：10.1055/s-2006-931797
[8]	Empson MB, Lassere M, Craig JC, et al. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant[J]. Cochrane Database Syst Rev, 2012, 2012(2): 2859.
[9]	Kaandorp S, Di Nisio M, Goddijn M, et al. Aspirin or anticoagulants for treating recurrent miscarriage in women without antiphospholipid syndrome[J]. Cochrane Database Syst Rev, 2009(1): 4734. doi：10.1002/14651858.cd004734.pub3
[10]	Chan YY, Jayaprakasan K, Tan A, et al. Reproductive outcomes in women with congenital uterine anomalies: a systematic review[J]. Ultrasound Obstet & Gyne, 2011, 38(4): 371-82. doi：10.1002/uog.10056
[11]	Wang SW, Zhong SY, Lou LJ, et al. The effect of intravenous immunoglobulin passive immunotherapy on unexplained recurrent spontaneous abortion: a meta-analysis[J]. Reprod BioMedicine Online, 2016, 33(6): 720-36. doi：10.1016/j.rbmo.2016.08.025
[12]	Liu ZL, Xu HJ, Kang XM, et al. Allogenic lymphocyte immunotherapy for unexplained recurrent spontaneous abortion: a meta-analysis[J]. American J Rep Immunol, 2016, 76(6): 443-53. doi：10.1111/aji.12511
[13]	de Jong PG, Goddijn M, Middeldorp S. Antithrombotic therapy for pregnancy loss[J]. Hum Reprod Update, 2013, 19(6): 656-73. doi：10.1093/humupd/dmt019
[14]	Ou H, Yu Q. Efficacy of aspirin, prednisone, and multivitamin triple therapy in treating unexplained recurrent spontaneous abortion: a cohort study[J]. Int J Gynecol Obstet, 2020, 148(1): 21-6. doi：10.1002/ijgo.12972
[15]	Saccone G, Schoen C, Franasiak JM, et al. Supplementation with progestogens in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials[J]. Fertil Steril, 2017, 107(2): 430-8.e3. doi：10.1016/j.fertnstert.2016.10.031
[16]	Tavakoli M, Jeddi-Tehrani M, Salek-Moghaddam A, et al. Effects of 1, 25(OH)₂ vitamin D3 on cytokine production by endometrial cells of women with recurrent spontaneous abortion[J]. Fertil Steril, 2011, 96(3): 751-7. doi：10.1016/j.fertnstert.2011.06.075
[17]	Hekmatdoost A, Vahid F, Yari Z, et al. Methyltetrahydrofolate vs folic acid supplementation in idiopathic recurrent miscarriage with respect to methylenetetrahydrofolate reductase C677T and A1298C polymorphisms: a randomized controlled trial[J]. PLoS One, 2015, 10(12): e0143569. doi：10.1371/journal.pone.0143569
[18]	Li TC. Recurrent miscarriage: aetiology, management and prognosis[J]. Hum Reprod Update, 2002, 8(5): 463-81. doi：10.1093/humupd/8.5.463
[19]	Tavoli Z, Mohammadi M, Tavoli A, et al. Quality of life and psychological distress in women with recurrent miscarriage: a comparative study[J]. Health Qual Life Outcomes, 2018, 16(1): 150. doi：10.1186/s12955-018-0982-z
[20]	Ji L, Brkić J, Liu M, et al. Placental trophoblast cell differentiation: Physiological regulation and pathological relevance to preeclampsia[J]. Mol Aspects Med, 2013, 34(5): 981-1023. doi：10.1016/j.mam.2012.12.008
[21]	Staun-Ram E, Shalev E. Human trophoblast function during the implantation process[J]. Reprod Biol Endocrinol, 2005, 3(1): 56. doi：10.1186/1477-7827-3-56
[22]	Tian FJ, Qin CM, Li XC, et al. Decreased stathmin-1 expression inhibits trophoblast proliferation and invasion and is associated with recurrent miscarriage[J]. Am J Pathol, 2015, 185(10): 2709-21. doi：10.1016/j.ajpath.2015.06.010
[23]	Ding JL, Cheng YX, Zhang Y, et al. The miR-27a-3p/USP25 axis participates in the pathogenesis of recurrent miscarriage by inhibiting trophoblast migration and invasion[J]. J Cell Physiol, 2019, 234(11): 19951-63. doi：10.1002/jcp.28593
[24]	Jordan NV, Johnson GL, Abell AN. Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer[J]. Cell Cycle, 2011, 10(17): 2865-73. doi：10.4161/cc.10.17.17188
[25]	Knöfler M, Pollheimer J. Human placental trophoblast invasion and differentiation: a particular focus on Wnt signaling[J]. Front Genet, 2013, 4: 190. doi：10.3389/fgene.2013.00190
[26]	Kokkinos MI, Murthi P, Wafai R, et al. Cadherins in the human placenta-epithelial-mesenchymal transition (EMT) and placental development[J]. Placenta, 2010, 31(9): 747-55. doi：10.1016/j.placenta.2010.06.017
[27]	Chen ZY, Li Z, Zong Y, et al. Exosome-delivered miR-410-3p reverses epithelial-mesenchymal transition, migration and invasion of trophoblasts in spontaneous abortion[J]. J Cellular Molecular Medi, 2024, 28(3): e18097. doi：10.1111/jcmm.18097
[28]	Yang GY, Luo H, Liao X, et al. Chinese herbal medicine for the treatment of recurrent miscarriage: a systematic review of randomized clinical trials[J]. BMC Complementary Altern Med, 2013, 13(1): 320. doi：10.1186/1472-6882-13-320
[29]	Zhu XH, Zhao L, Fu JH, et al. “Nourishing the kidney” and the treatment of recurrent pregnancy loss using traditional Chinese medicine[J]. Int J Gynecol Obstet, 2014, 127(1): 90-1. doi：10.1016/j.ijgo.2014.06.002
[30]	Piao L, Chen CP, Yeh CC, et al. Chinese herbal medicine for miscarriage affects decidual micro-environment and fetal growth[J]. Placenta, 2015, 36(5): 559-66. doi：10.1016/j.placenta.2015.02.006
[31]	Li L, Dou LX, Leung PC, et al. Chinese herbal medicines for unexplained recurrent miscarriage[J]. Cochrane Database Syst Rev, 2016: 10568. doi：10.1002/14651858.cd010568.pub2
[32]	Yang SL, Niu TT, Li XL, et al. Bu-Shen-Yi-Qi formula impairs cytotoxicity of NK cells by up-regulating IDO expression in trophoblasts[J]. Gynecol Endocrinol, 2018, 34(8): 675-9. doi：10.1080/09513590.2018.1425988
[33]	Sun DQ, Lu SJ, Gan XW, et al. Is there a place for Traditional Chinese Medicine (TCM) in the treatment of recurrent pregnancy loss?[J]. J Reprod Immunol, 2022, 152: 103636. doi：10.1016/j.jri.2022.103636
[34]	Zhou H, Yang Y, Deng LW, et al. A potential mechanism of kidney-tonifying herbs treating unexplained recurrent spontaneous abortion: clinical evidence from the homogeneity of embryo implantation and tumor invasion[J]. Front Pharmacol, 2022, 12: 775245. doi：10.3389/fphar.2021.775245
[35]	Alvarez-Erviti L, Seow Y, Yin HF, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes[J]. Nat Biotechnol, 2011, 29(4): 341-5. doi：10.1038/nbt.1807
[36]	Kamerkar S, LeBleu VS, Sugimoto H, et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer[J]. Nature, 2017, 546(7659): 498-503. doi：10.1038/nature22341
[37]	Zhang R, Fu YX, Cheng M, et al. sEVsRVG selectively delivers antiviral siRNA to fetus brain, inhibits ZIKV infection and mitigates ZIKV-induced microcephaly in mouse model[J]. Mol Ther, 2022, 30(5): 2078-91. doi：10.1016/j.ymthe.2021.10.009
[38]	Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition[J]. Nat Rev Mol Cell Biol, 2014, 15(3): 178-96. doi：10.1038/nrm3758
[39]	Savagner P. Epithelial-mesenchymal transitions[M]//Cellular Adhesion in Development and Disease. Amsterdam: Elsevier, 2015: 273-300. doi：10.1016/bs.ctdb.2014.11.021
[40]	Pei DQ, Shu XD, Gassama-Diagne A, et al. Mesenchymal-epithelial transition in development and reprogramming[J]. Nat Cell Biol, 2019, 21(1): 44-53. doi：10.1038/s41556-018-0195-z
[41]	DaSilva-Arnold S, James JL, Al-Khan A, et al. Differentiation of first trimester cytotrophoblast to extravillous trophoblast involves an epithelial-mesenchymal transition[J]. Placenta, 2015, 36(12): 1412-8. doi：10.1016/j.placenta.2015.10.013
[42]	Lee KM, Seo HW, Kwon MS, et al. SIRT1 negatively regulates invasive and angiogenic activities of the extravillous trophoblast[J]. American J Rep Immunol, 2019, 82(4): e13167. doi：10.1111/aji.13167
[43]	Shenoy AK, Jin Y, Luo HC, et al. Epithelial-to-mesenchymal transition confers pericyte properties on cancer cells[J]. J Clin Investig, 2016, 126(11): 4174-86. doi：10.1172/jci86623
[44]	Ding JL, Zhang Y, Cai XP, et al. Extracellular vesicles derived from M1 macrophages deliver miR-146a-5p and miR-146b-5p to suppress trophoblast migration and invasion by targeting TRAF6 in recurrent spontaneous abortion[J]. Theranostics, 2021, 11(12): 5813-30. doi：10.7150/thno.58731
[45]	Lee HJ, Lim SM, Jang HY, et al. miR-373-3p regulates invasion and migration abilities of trophoblast cells via targeted CD44 and radixin[J]. Int J Mol Sci, 2021, 22(12): 6260. doi：10.3390/ijms22126260
[46]	Ben-Shushan D, Markovsky E, Gibori H, et al. Overcoming obstacles in microRNA delivery towards improved cancer therapy[J]. Drug Deliv Transl Res, 2014, 4(1): 38-49. doi：10.1007/s13346-013-0160-0
[47]	Zhou DZ, Cutlar L, Gao YS, et al. The transition from linear to highly branched poly(β-amino ester)s: Branching matters for gene delivery[J]. Sci Adv, 2016, 2(6): e1600102. doi：10.1126/sciadv.1600102
[48]	Liu S, Sun ZB, Zhou DZ, et al. Alkylated branched poly(β-amino esters) demonstrate strong DNA encapsulation, high nanoparticle stability and robust gene transfection efficacy[J]. J Mater Chem B, 2017, 5(27): 5307-10. doi：10.1039/c7tb00996h
[49]	Lim EK, Jang E, Lee K, et al. Delivery of cancer therapeutics using nanotechnology[J]. Pharmaceutics, 2013, 5(2): 294-317. doi：10.3390/pharmaceutics5020294
[50]	Feng L, Mumper RJ. A critical review of lipid-based nanoparticles for taxane delivery[J]. Cancer Lett, 2013, 334(2): 157-75. doi：10.1016/j.canlet.2012.07.006
[51]	Sadasivam M, Avci P, Gupta GK, et al. Self-assembled liposomal nanoparticles in photodynamic therapy[J]. ejnm, 2013, 5(3): 115-29. doi：10.1515/ejnm-2013-0010
[52]	Ha D, Yang NN, Nadithe V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges[J]. Acta Pharm Sin B, 2016, 6(4): 287-96. doi：10.1016/j.apsb.2016.02.001
[53]	Rani S, Ritter T. The exosome-a naturally secreted nanoparticle and its application to wound healing[J]. Adv Mater, 2016, 28(27): 5542-52. doi：10.1002/adma.201504009
[54]	Aqil F, Munagala R, Jeyabalan J, et al. Milk exosomes-Natural nanoparticles for siRNA delivery[J]. Cancer Lett, 2019, 449: 186-95. doi：10.1016/j.canlet.2019.02.011
[55]	Yan CQ, Chen J, Wang C, et al. Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis[J]. Drug Deliv, 2022, 29(1): 214-28. doi：10.1080/10717544.2021.2023699
[56]	Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases[J]. Science, 2002, 298(5600): 1911-2. doi：10.1126/science.1072682
[57]	Cuenda A, Rousseau S. p38 MAP-Kinases pathway regulation, function and role in human diseases[J]. Biochim Biophys Acta BBA Mol Cell Res, 2007, 1773(8): 1358-75. doi：10.1016/j.bbamcr.2007.03.010
[58]	Cuadrado A, Nebreda AR. Mechanisms and functions of p38 MAPK signalling[J]. Biochem J, 2010, 429(3): 403-17. doi：10.1042/bj20100323
[59]	Takanami-Ohnishi Y, Asada S, Tsunoda H, et al. Possible involvement of p38 mitogen-activated protein kinase in decidual function in parturition[J]. Biochem Biophys Res Commun, 2001, 288(5): 1155-61. doi：10.1006/bbrc.2001.5895
[60]	Chen GL, Ye XY, Zhang JW, et al. Limb remote ischemic postconditioning reduces ischemia-reperfusion injury by inhibiting NADPH oxidase activation and MyD88-TRAF6-P38MAP-kinase pathway of neutrophils[J]. Int J Mol Sci, 2016, 17(12): 1971. doi：10.3390/ijms17121971
[61]	Tang L, Li XD, Bai YH, et al. microRNA-146a negatively regulates the inflammatory response to Porphyromonas gingivalis in human periodontal ligament fibroblasts via TRAF6/p38 pathway[J]. J Periodontol, 2019, 90(4): 391-9. doi：10.1002/jper.18-0190
[62]	Li Y, Liu XY, Wang JL, et al. Effects of shoutai pill containing serum on bioactivity behavior of trophoblast cells of spontaneous abortion patients[J]. Chin J Chinese Materia Med, 2016, 36(5): 586-91.
[63]	Lai MH. Effects of Shoutai pills on expression of Th1/Th2 cytokine in maternal-fetal interface and pregnancy outcome[J]. China J Chin Mater Med, 2010: 3065-8. doi：10.4268/cjcmm20102229
[64]	Li HF, Shen QH, Li XQ, et al. The efficacy of traditional Chinese medicine Shoutai pill combined with western medicine in the first trimester of pregnancy in women with unexplained recurrent spontaneous abortion: a systematic review and meta-analysis[J]. BioMed Res Int, 2020, 2020: 7495161. doi：10.1155/2020/7495161
[65]	Lai YL, Zhang Y, Zhang HM, et al. Modified Shoutai Pill inhibited ferroptosis to alleviate recurrent pregnancy loss[J]. J Ethnopharmacol, 2024, 319: 117028. doi：10.1016/j.jep.2023.117028

减味寿胎丸通过抑制Exo-miR-410-3p摄取促进滋养细胞上皮间质转化、迁移及侵袭减少胚胎流产

Jianwei Shoutai Pill reduces spontaneous abortion in mice by inhibiting Exo-miR-410-3p uptake and promoting trophoblast epithelial-mesenchymal transition, migration, and invasion

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 15

参考文献 65

相关文章 15

编辑推荐

Metrics

本文评价

[1]	周仁杰, 杨晶晶, 宋博文, 陈孝华, 王炼, 王月月, 左芦根, 朱冰. 高表达PSMD11促进胃癌细胞上皮-间质转化进程并影响患者预后[J]. 南方医科大学学报, 2025, 45(12): 2747-2755.
[2]	姜雪凝, 黄晴晴, 徐盈, 王舜印, 张小凤, 王炼, 王月月, 左芦根. 高表达YEATS2通过激活Wnt/β-catenin通路促进胃癌细胞上皮-间质转化进程[J]. 南方医科大学学报, 2025, 45(11): 2416-2426.
[3]	张文静, 张诺, 杨子, 张小凤, 孙奥飞, 王炼, 宋雪, 耿志军, 李静, 胡建国. BZW1 高表达促进胃癌细胞的侵袭和转移：基于调控Wnt//β-catenin通路和促进上皮间质转化[J]. 南方医科大学学报, 2024, 44(2): 354-362.
[4]	左芦根, 王炼, 杨子, 李骏杰, 王文锋, 李静, 王月月, 宋雪, 张小凤, 耿志军. 高表达CAMSAP2通过上调TGF-β信号促进胃癌细胞的侵袭和转移[J]. 南方医科大学学报, 2023, 43(9): 1460-1468.
[5]	孙建华, 张逸, 杨丽萍, 周立, 卢喜洋, 李久现, 陈萍. 尿路上皮癌抗原1促进滋养细胞功能及对上皮-间质转化转化的调控作用[J]. 南方医科大学学报, 2023, 43(11): 1984-1988.
[6]	林杰, 区活辉, 王卫东, 马靖, 张伟杰, 刘清波. 过表达CLEC5A基因抑制肝细胞癌增殖和转移并逆转上皮-间质转化[J]. 南方医科大学学报, 2023, 43(1): 85-91.
[7]	朱显军, 罗喜俊, 李涛, 梁俊杰, 何嘉琳, 唐兴奎. LINC01285促进结直肠癌细胞的增殖和转移[J]. 南方医科大学学报, 2022, 42(11): 1697-1704.
[8]	何建萍, 李晓娟, 吕梦欣, 王珏, 唐健, 罗胜军, 钱源. ALKBH5通过抑制上皮-间质转化降低人滋养细胞的迁移和侵袭能力[J]. 南方医科大学学报, 2020, 40(12): 1720-1725.
[9]	刘惠莉, 王一丹, 岳阳丽, 张朋, 孙亚丽, 陈巧华. 骨膜素通过p38 MAPK信号通路抑制缺氧诱导的人牙周膜成纤维细胞的氧化应激和细胞凋亡[J]. 南方医科大学学报, 2020, 40(07): 942-948.
[10]	全景羽，卢子滨，余林中，范春林，曹惠慧，刘俊珊. 外泌体对上皮-间质转化调控作用的研究进展[J]. 南方医科大学学报, 2019, 39(03): 377-.
[11]	陈海平，向玘，刘大伟，魏强. 沉默CIT基因可抑制前列腺癌细胞的增殖和转移[J]. 南方医科大学学报, 2019, 39(03): 257-.
[12]	周丹，许鹏程，张敏，于洋，吴爱国. 色素上皮衍生因子通过调控上皮间质转化抑制乳腺癌细胞侵袭和转移[J]. 南方医科大学学报, 2018, 38(01): 1-.
[13]	王卫华，王昌正，蒋一，吴本俨. miR-92b 对人胃癌细胞SGC7901迁移、粘附和侵袭的影响[J]. 南方医科大学学报, 2014, 34(12): 1748-.
[14]	晁远，翁立冬，曾嵘. 基因组DNA甲基化水平与不明原因早期自然流产的相关性[J]. 南方医科大学学报, 2014, 34(10): 1498-.
[15]	宋兰林，熊丽，刘思平，刘洁，钟梅，高云飞，吴瑞枫，余艳红. FISH技术在快速诊断自然流产胚胎染色体数目异常中的应用[J]. 南方医科大学学报, 2011, 31(09): 1605-.