Effect of Yangxue Antai prescription on the regulation of placental angiogenesis and autophagy in recurrent spontaneous abortion mice

doi:10.19803/j.1672-8629.20240058

Abstract

Abstract: Objective To explore the molecular mechanism of Recurrent spontaneous abortion (RSA) treated by Yangxue Antai prescription. Methods RSA mouse model with kidney deficiency and blood stasis was constructed, and the placentas of mice were collected after the intervention of Yangxue Antai prescription, The pathological changes of mouse placenta were observed by HE staining and Masson staining, and the expressions of PCNA, Fibrinogen and CD34 protein in mouse placenta were determined by immunohistochemistry. The protein expression of VEGF, p-VEGFR2, p62, Beclin1, LC3Ⅰ and LC3Ⅱ in mouse placenta were determined by Western blot. The ultrastructure of mouse placenta was observed by transmission electron microscopy (TEM). Results Compared with RSA group, the body weight of mice in RSA+ Yangxue Antai group increased significantly, and the embryo absorption rate decreased significantly. HE staining, Masson staining and the expression of PCNA and Fibrinogen protein showed significantly improve in mice placenta. TEM results and the protein expression of p62, Beclin1, LC3II/LC3Ⅰ showed that the level of autophagy of the placenta of the mice was significantly decreased. CD34, VEGFA and p-VEGFR2 proteins expression showed a significant increase in placental angiogenesis. Conclusion Yangxue Antai prescription improve placental development and promote placental angiogenesis in RSA mice, which may be related to inhibiting the fusion of autophagosome and lysosome, thus inhibiting autophagy.

Key words: Yangxue Antai prescription, recurrent spontaneous abortion, angiogenesis, autophagy, kidney deficiency and blood stasis, herbal compounding, mice, placenta

CLC Number:

R965

YAO Weijie, YAN Shiqi, YUAN Sisi, GONG Leilei, FENG Xin. Effect of Yangxue Antai prescription on the regulation of placental angiogenesis and autophagy in recurrent spontaneous abortion mice[J]. Chinese Journal of Pharmacovigilance, 2024, 21(4): 371-377.

Add to citation manager EndNote|Ris|BibTeX

URL: https://www.zgywjj.com/EN/10.19803/j.1672-8629.20240058

https://www.zgywjj.com/EN/Y2024/V21/I4/371

References

[1] DIMITRIADIS E, MENKHORST E, SAITO S, et al.Recurrent pregnancy loss[J]. Nat Rev Dis Primers, 2020, 6(1): 98.
[2] HONG LY, MARREN A.Recurrent pregnancy loss: a summary of international evidence-based guidelines and practice[J]. Aust J Gen Pract, 2018, 47(7): 432-436.
[3] SINGH N, PRASAD P, DAS B.Does tumour necrosis factor alpha-induced cyclooxygenase-2 expression lead to spontaneous abortion in Chlamydia trachomatis-infected women[J]. Microb Pathog, 2020, 142: 103994.
[4] ISHII T, MIYAZAWA M, TAKANASHI Y, et al.Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion[J]. Redox Biol, 2014, 2: 679-685.
[5] HE JQ, LI MJ, WANG YW, et al.Intervention of integrated Chinese and western medicine on prethrombotic state in recurrent spontaneous abortion with Yangxue Antai Granules[J]. World Journal of Integrated Traditional and Western Medicine(世界中西医结合杂志), 2014, 9(6): 620-623.
[6] LI ET, LI MJ, GAO AP, et al.Effect of Yangxue Antai granule in prevnting and treating habitual abortion and its effect on short life T-suppressor cell[J]. Chinese Journal of Integrated Traditional and Western Medicine(中国中西医结合杂志), 2000, 20(4): 248-250.
[7] YAO WJ, DU BY, LI X, et al.Effect of Yangxue Antai granules on inhibiting miR-16 in exosomes to promote angiogenesis[J]. Global Traditional Chinese Medicine(环球中医药),2022(5): 745-751.
[8] LOKESWARA AW, HIKSAS R, IRWINDA R, et al.Preeclampsia: from cellular wellness to inappropriate cell death, and the roles of nutrition[J]. Front Cell Dev Biol, 2021, 9: 726513.
[9] HONG L, ZHU YC, LIU S, et al.Multi-omics reveals a relationship between endometrial amino acid metabolism and autophagy in women with recurrent miscarriage[J]. Biol Reprod, 2021, 105(2): 393-400.
[10] PAN YB, YAN LL, CHEN QQ, et al.Dysfunction of Shh signaling activates autophagy to inhibit trophoblast motility in recurrent miscarriage[J]. Exp Mol Med, 2021, 53(1): 52-66.
[11] YANG Y, HU ZY, DU XX, et al.miR-16 and fluoxetine both reverse autophagic and apoptotic change in chronic unpredictable mild stress model rats[J]. Front Neurosci, 2017, 11: 428.
[12] WILLIAMS CJ, CHU A, JEFFERSON WN, et al.Epithelial membrane protein 2 (EMP2) deficiency alters placental angiogenesis, mimicking features of human placental insufficiency[J]. J Pathol, 2017, 242: 246-259.
[13] MIRIANA C, CARLA T, ENNIO P.Targeting proliferating cell nuclear antigen (PCNA) as an effective strategy to inhibit tumor cell proliferation[J]. Curr Cancer Drug Targets, 2020, 4(20): 240-252.
[14] SANO T, TERAI Y, DAIMON A, et al.Recombinant human soluble thrombomodulin as an anticoagulation therapy improves recurrent miscarriage and fetal growth restriction due to placental insufficiency the leading cause of preeclampsia[J]. Placenta, 2018, 65: 1-6.
[15] ZHI Z, YANG W, LIU L, et al.Early missed abortion is associated with villous angiogenesis via the HIF-1α/ VEGF signaling pathway[J]. Arch Gynecol Obstet, 2018, 298(3): 537-543.
[16] SONG P, HAI Y, WANG X, et al.Realgar transforming solution suppresses angiogenesis and tumor growth by inhibiting VEGF receptor 2 signaling in vein endothelial cells[J]. Arch Pharm Res, 2018, 41(4): 467-480.
[17] PRERNA K, DUBEY VK.Beclin1-mediated interplay between autophagy and apoptosis: new understanding[J]. Int J Biol Macromol, 2022, 204: 258-273.
[18] KAGEYAMA S, GUDMUNDSSON SR, SOU YS, et al.p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response[J]. Nat Commun, 2021, 12(1): 16.
[19] ASARE PF, ROSCIOLI E, HURTADO PR, et al.LC3-associated phagocytosis (LAP): a potentially influential mediator of efferocytosis-related tumor progression and aggressiveness[J]. Front Oncol, 2020, 10: 1298.