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补肾调血颗粒和坤灵丸对控制性卵巢过度刺激后大鼠受损血管生成和子宫内膜容受性的改善作用。

The ameliorating effects of Bushen Tiaoxue Granules and Kunling Wan on impaired angiogenesis and endometrial receptivity in rats following controlled ovarian hyperstimulation.

机构信息

Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing, China.

Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China.

出版信息

Microcirculation. 2020 Jan;27(1):e12581. doi: 10.1111/micc.12581. Epub 2019 Oct 3.

Abstract

OBJECTIVE

To investigate the effects of Bushen Tiaoxue Granules and Kunling Wan, the two Chinese medicines, on vascular dysfunction and the impairment of endometrial receptivity caused by controlled ovarian hyperstimulation and its underlying mechanism.

METHODS

Female Sprague Dawley rats with regular estrous cycle were enrolled and given Bushen Tiaoxue Granules or Kunling Wan by gavage for 12 days, and then, controlled ovarian hyperstimulation model was induced. We assessed endometrial microvessels, endometrial blood flow, levels of estradiol and progesterone in serum, vascular endothelial growth factor A upstream molecules estrogen and progesterone receptors in the endometrium, and pregnancy outcome.

RESULTS

Pre-treatment of Bushen Tiaoxue Granules or Kunling Wan increases endometrial blood flow of controlled ovarian hyperstimulation rats, up-regulates vascular endothelial growth factor A and microvessels, improves the endometrial morphology of controlled ovarian hyperstimulation rats during implantation, decreases the super physiological concentration of estradiol and progesterone in serum, and increases the expression of vascular endothelial growth factor A upstream molecules estrogen and progesterone receptors in the endometrium. In addition, Bushen Tiaoxue Granules or Kunling Wan elevates the lysophosphatidic acid receptor 3 that participates in vascularization and increases the expression of leukemia inhibitory factor through up-regulating the expression of p53 in the endometrium, ultimately affecting pregnancy outcome.

CONCLUSION

This study demonstrated Bushen Tiaoxue Granules or Kunling Wan as a potential strategy for prevention of impairment in angiogenesis and endometrial receptivity induced by controlled ovarian hyperstimulation.

摘要

目的

探讨补肾调血颗粒和坤灵丸这两种中药对卵巢控制性超刺激引起的血管功能障碍和子宫内膜容受性损伤的作用及其机制。

方法

选取动情周期正常的雌性 Sprague Dawley 大鼠,经灌胃给予补肾调血颗粒或坤灵丸 12 天,建立卵巢控制性超刺激模型。评估子宫内膜微血管、血清中雌二醇和孕酮水平、子宫内膜中血管内皮生长因子 A 的上游分子雌激素和孕激素受体,以及妊娠结局。

结果

补肾调血颗粒或坤灵丸预处理可增加卵巢控制性超刺激大鼠的子宫内膜血流,上调血管内皮生长因子 A 和微血管,改善着床期卵巢控制性超刺激大鼠的子宫内膜形态,降低血清中超生理浓度的雌二醇和孕酮,并增加子宫内膜中血管内皮生长因子 A 的上游分子雌激素和孕激素受体的表达。此外,补肾调血颗粒或坤灵丸通过上调子宫内膜中 p53 的表达,增加参与血管生成的溶血磷脂酸受体 3 和白血病抑制因子的表达,最终影响妊娠结局。

结论

本研究表明补肾调血颗粒和坤灵丸可能是预防卵巢控制性超刺激引起的血管生成和子宫内膜容受性损伤的一种策略。

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