中国药物警戒 ›› 2024, Vol. 21 ›› Issue (4): 371-377.
DOI: 10.19803/j.1672-8629.20240058

• 养血安胎方对复发性自然流产的作用机制研究专栏 • 上一篇    下一篇

养血安胎方对复发性自然流产小鼠胎盘血管生成与自噬的调控作用研究

姚伟洁1, 闫仕祺2, 袁偲偲1, 贡磊磊1, 冯欣1,*   

  1. 1首都医科大学附属北京妇产医院,北京妇幼保健院药事部,北京 100026;
    2首都医科大学中医药学院,中医络病研究北京市重点实验室,北京,100069
  • 收稿日期:2024-01-25 出版日期:2024-04-15 发布日期:2024-04-18
  • 通讯作者: * 冯欣,女,硕士,主任药师,药理学与医院药学。E-mail: fengxin1115@ccmu.edu.cn
  • 作者简介:姚伟洁,男,博士,主管药师,中药药理学。
  • 基金资助:
    国家自然科学基金资助项目(82204783); 北京妇产医院“中青年学科骨干培养专项”(FCYY202109)

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

YAO Weijie1, YAN Shiqi2, YUAN Sisi1, GONG Leilei1, FENG Xin1,*   

  1. 1Department of Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China;
    2 Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
  • Received:2024-01-25 Online:2024-04-15 Published:2024-04-18

摘要: 目的 探讨养血安胎方治疗复发性自然流产(RSA)的分子机制。方法 构建肾虚血瘀型RSA小鼠模型,养血安胎方干预后收集小鼠胎盘,苏木素伊红(HE)染色、马松(Masson)染色观察小鼠胎盘病理变化、免疫组化法测定小鼠胎盘增殖细胞核抗原(PCNA)、纤维蛋白原(Fibrinogen)及CD34蛋白的表达,Western blot法测定小鼠胎盘血管内皮生长因子(VEGF)、血管内皮细胞生长因子受体2(p-VEGFR2)、p62,Beclin 1,LC3Ⅰ和LC3Ⅱ的蛋白表达,透射电镜观察小鼠胎盘的超微结构。结果 与RSA组比较,RSA+养血安胎组小鼠取材时体重显著增加,胚胎吸收率显著降低;HE染色、Masson染色及PCNA、Fibrinogen蛋白表达显示小鼠胎盘发育状况明显改善,透射电镜结果与p62、Beclin1和LC3Ⅱ/LC3Ⅰ的蛋白表达显示小鼠胎盘自噬水平明显降低,CD34、VEGFA和p-VEGFR2蛋白表达显示胎盘血管生成明显增加。结论 养血安胎方能够改善RSA小鼠的胎盘发育状况,促进胎盘血管生成,其方式可能与抑制自噬体与溶酶体的融合,从而抑制自噬有关。

关键词: 养血安胎方, 复发性自然流产, 血管生成, 自噬, 肾虚血瘀, 中药复方, 小鼠, 胎盘

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

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