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孕康口服液对复发性流产小鼠内分泌系统及VEGF信号通路的调节作用、机制及降低流产率的研究

[Effect and mechanism of Yunkang oral liquid in regulating endocrine system and VEGF signaling pathway and reducing abortion rate in recurrent abortion mice].

作者信息

Chen Bo, Shi Qiu-Qiu, Liang Kai-Lun, Xu Yu-Yue, Fang Ying-Ying, Chen Su-Hong, Lyu Gui-Yuan

机构信息

Zhejiang Chinese Medical University, Hangzhou 310053, China.

Wenzhou Medical University, Wenzhou 325035, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2018 May;43(9):1894-1900. doi: 10.19540/j.cnki.cjcmm.2018.0064.

DOI:10.19540/j.cnki.cjcmm.2018.0064
PMID:29902902
Abstract

This experiment focuses on the effect of Yunkang oral liquid on abortion rate, endocrine system and VEGF signal pathway in Clark classical recurrent abortion model mice. RSA mice were randomly divded into model group, low, middle and high-dose groups and progesterone group. The normal pregnancy mice were included into normal group. Since the first day of pregnancy, the normal group and the RSA model group were given the same dose of distilled water, while low, middle and high-dose groups were given Yunkang oral liquid at the dose of 9, 18, 36 mL·kg¹·d⁻¹; progesterone group were given progesterone by 0.039 g·kg¹·d⁻¹. The mice were put to deathat the 15th day of pregnancy, and the embryo loss rate of each group was observed. Serum estradiol (E₂), progesterone (P), prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH) level were tested; the protein expressions of estrogen receptor(ER), progesterone receptor (PR), prolactin receptor (PRLR) in decidua and RAS, MAPK, VEGF, VEGFR-2 gene and protein expressions in deciduas were studied. The results showed that middle, high dose Yunkang and progesterone could significantly decrease the embryo loss rate of RSA mice. The levels of FSH, LH, PRL, P and E₂ in serum in Yunkang and progesterone groups were increased, and the serum levels of FSH, LH, and E₂ in Yunkang group were higher than those in progesterone group. Western blot analysis showed that Yunkang oral liquid and progesterone can significantly increase the expressions of PRLR, PR in the uterine decidua of RSA mice, and the expression of ER in Yunkang group was higher than that in progesterone group. Western blot and PCR showed that the Yunkang oral liquid and progesterone can significantly increase RAS, MAPK, VEGF, VEGFR-2 gene and protein expressions in the uterine decidua of RSA mice. The results showed that Yunkang oral liquid can effectively reduce the embryo loss rate of RSA model mice, increase the levels of FSH, LH, PRL, P and E₂ in serum, promote the expressions of PRLR, PR, ER protein in decidua and the RAS, MAPK, VEGF, VEGFR-2 gene and protein expressions in the decidua, improve the vascular remodeling of fetal interface, the endometrial receptivty, the development of decidua and the blastocyst implantation.

摘要

本实验聚焦于孕康口服液对Clark经典复发性流产模型小鼠流产率、内分泌系统及VEGF信号通路的影响。将复发性流产小鼠随机分为模型组、低、中、高剂量组及黄体酮组,正常妊娠小鼠纳入正常组。自妊娠第1天起,正常组和复发性流产模型组给予相同剂量蒸馏水,低、中、高剂量组分别给予剂量为9、18、36 mL·kg⁻¹·d⁻¹的孕康口服液;黄体酮组给予0.039 g·kg⁻¹·d⁻¹的黄体酮。于妊娠第15天处死小鼠,观察各组胚胎丢失率。检测血清雌二醇(E₂)、孕酮(P)、催乳素(PRL)、黄体生成素(LH)、卵泡刺激素(FSH)水平;研究蜕膜中雌激素受体(ER)、孕酮受体(PR)、催乳素受体(PRLR)蛋白表达以及蜕膜中RAS、MAPK、VEGF、VEGFR - 2基因和蛋白表达。结果显示,中、高剂量孕康口服液及黄体酮可显著降低复发性流产小鼠的胚胎丢失率。孕康口服液组和黄体酮组血清中FSH、LH、PRL、P及E₂水平升高,且孕康口服液组血清FSH、LH及E₂水平高于黄体酮组。蛋白质印迹分析表明,孕康口服液和黄体酮可显著增加复发性流产小鼠子宫蜕膜中PRLR、PR的表达,且孕康口服液组ER表达高于黄体酮组。蛋白质印迹及PCR结果显示,孕康口服液和黄体酮可显著增加复发性流产小鼠子宫蜕膜中RAS、MAPK、VEGF、VEGFR - 2基因和蛋白表达。结果表明,孕康口服液可有效降低复发性流产模型小鼠胚胎丢失率,提高血清中FSH、LH、PRL、P及E₂水平,促进蜕膜中PRLR、PR、ER蛋白表达以及蜕膜中RAS、MAPK、VEGF、VEGFR - 2基因和蛋白表达,改善胎儿界面血管重塑、子宫内膜容受性、蜕膜发育及胚泡着床。

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引用本文的文献

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Efficacy and safety of Yunkang oral liquid combined with conventional therapy for threatened miscarriage of first-trimester pregnancy a protocol for systematic review and meta-analysis.孕康口服液联合常规疗法治疗早期先兆流产的疗效和安全性:系统评价和 Meta 分析方案。
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