中国药物警戒 ›› 2024, Vol. 21 ›› Issue (5): 547-552.
DOI: 10.19803/j.1672-8629.20240061

• 基础与临床研究 • 上一篇    下一篇

养血安胎方调节自噬改善复发性自然流产小鼠子宫内膜上皮细胞间质转化及蜕膜化的作用研究

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:2024-05-15 发布日期:2024-05-13
  • 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）

Roles of Yangxue Antai prescription in improving endometrial epithelial-mesenchymal transformation and decidualization in recurrent spontaneous abortion mice by regulating autophagy

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;
    2Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
  • Received:2024-01-25 Online:2024-05-15 Published:2024-05-13

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摘要： 目的 探讨养血安胎方调节自噬改善复发性自然流产（RSA）小鼠子宫内膜上皮细胞-间质转化（EMT）及蜕膜化的作用。方法 构建肾虚血瘀型RSA小鼠以及正常妊娠小鼠,正常妊娠小鼠分别腹腔注射2 mg·kg-1雷帕霉素（Rapa）溶液或15 mg·kg-1 3-甲基腺嘌呤（3-MA）溶液进行干预;另设置相同方法处理的RSA小鼠、Rapa及3-MA干预的小鼠组,并同时灌胃给药浓度为28.08 g·kg-1的养血安胎溶液进行干预,收集小鼠子宫内膜。通过Western blot法测定小鼠子宫内膜EMT相关蛋白E-cadherin、Vimentin、N-cadherin和Fibronectin的表达,以及蜕膜化相关蛋白BMP2、HOXA10、PRL和IGFBP1的表达。结果 与正常妊娠组比较,RSA组小鼠子宫内膜中E-cadherin的蛋白表达显著增加,Vimentin、N-cadherin、Fibronectin、BMP2、HOXA10、PRL和IGFBP1的蛋白表达均显著降低;Rapa组小鼠子宫内膜中E-cadherin的蛋白表达显著增加,Vimentin、N-cadherin、Fibronectin、BMP2、HOXA10、PRL和IGFBP1的蛋白表达均显著降低;3-MA组小鼠子宫内膜中E-cadherin的蛋白表达显著降低,HOXA10的蛋白表达显著增加。与RSA组比较,RSA+养血安胎组小鼠子宫内膜中E-cadherin的蛋白表达显著降低,Vimentin、N-cadherin、Fibronectin、BMP2、HOXA10、PRL和IGFBP1的蛋白表达均显著增加。与Rapa组比较,Rapa+养血安胎组小鼠子宫内膜中E-cadherin的蛋白表达显著降低,Vimentin、N-cadherin、Fibronectin、BMP2、HOXA10、PRL和IGFBP1的蛋白表达均显著增加。结论 养血安胎方能够抑制自噬,从而促进妊娠小鼠子宫内膜的EMT及蜕膜化过程,降低流产率。

关键词: 养血安胎方, 雷帕霉素, 3-甲基腺嘌呤, 复发性自然流产, 自噬, 胚胎植入, 上皮细胞-间质转化, 蜕膜化, 中药复方, 小鼠

Abstract: Objective To explore the role of Yangxue Antai prescription in improving endometrial epithelial-mesenchymal transformation (EMT) and decidualization in mice with recurrent spontaneous abortion (RSA) by regulating autophagy. Methods An RSA mouse model with kidney deficiency and blood stasis was established before the normal pregnant mice were intraperitoneally injected 2 mg·kg-1 rapamycin (Rapa) solution or 15 mg·kg-1 3-methyladenine (3-MA) solution, respectively; RSA mice, Rapa mice and 3-MA mice treated with the same method were also set up, and the concentration of 28.08 g·kg-1 of Yangxue Antai Prescription was given at the same time for intervention, then the endometrium of the mice was collected. The expressions of EMT-related proteins E-cadherin, Vimentin, N-cadherin, and Fibronectin, as well as deciduation-related proteins BMP2, HOXA10, PRL, and IGFBP1 were measured by Western blot. Results Compared with the normal pregnancy group, the expression of E-cadherin in the endometrium of mice in the RSA group was significantly increased, while the expressions of Vimentin, N-cadherin, Fibronectin, BMP2, HOXA10, PRL and IGFBP1 were significantly decreased. The expression of E-cadherin in the endometrium of the Rapa group was significantly increased, while those of Vimentin, N-cadherin, Fibronectin, BMP2, HOXA10, PRL and IGFBP1 were significantly decreased. The protein expression of E-cadherin in the endometrium of the 3-MA group was significantly decreased while that of HOXA10 was significantly increased. Compared with the RSA group, the expression of E-cadherin in the the endometrium of mice in the RSA+ YXAT group was significantly decreased, while the expressions of Vimentin, N-cadherin, Fibronectin, BMP2, HOXA10, PRL and IGFBP1 were significantly increased. Compared with the Rapa group, the expression of E-cadherin in the endometrium of mice in the Rapa+ YXAT group was significantly decreased, while those of Vimentin, N-cadherin, Fibronectin, BMP2, HOXA10, PRL and IGFBP1 were significantly increased. Conclusion Yangxue Antai prescription can inhibit autophagy, promote EMT and decidualization process of the endometrium of pregnant mice, and reduce abortion rate.

Key words: Yangxue Antai prescription, rapamycin, 3-methyladenine, embryo implantation, recurrent spontaneous abortion, autophagy, epithelial-mesenchymal transformation, decidualization, herbal compounding, mice

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