Yijing Decoction improves premature ovarian failure in rats by activating VEGF/VEGFR-2/FAK pathway.

IF 3.8 3区 医学 Q1 REPRODUCTIVE BIOLOGY
Ranran Gao, Yeke Wu, Yuqin Tang, Keming Wu, Baojun Guo
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引用次数: 0

Abstract

Background: Premature ovarian failure (POF) is defined as amenorrhea that occurs before the age of 40 when the ovaries weaken or even fail. This disease seriously affects a woman's future health and fertility.

Methods: Potential targets of Yijing Decoction (YJD) and POF were predicted by web-based pharmacology-related databases. The POF rat models and human ovarian granulosa cells injury models were induced by triptolide. In addition, the estrous cycle of the rats was monitored by vaginal smear and the ovarian tissue morphology was stained by HE staining. Immunohistochemistry, qRT-PCR and Western blotting were used to evaluate the levels of reproductive and angiogenesis related factors. Moreover, serum levels of the sex hormones and the oxidative stress indicators were measured by ELISA.

Results: YJD treatment resulted in the improvement of triptolide-induced abnormal ovarian function by restoring normal estrous cycle, maintaining nearly normal ovarian size, reducing follicular atresia and increasing vascularization. Additionally, YJD treatment normalized the serum levels of P, E2, FSH, LH, AMH, MDA and SOD, while activating the VEGF/VEGFR-2/FAK pathway. However, the VEGF/VEGFR-2/FAK pathway inhibitors reversed these pharmacological effects that YJD exhibited in POF rats. Furthermore, YJD increased the pregnancy rate and the number of live births in POF rats.

Conclusion: YJD reduced oxidative stress level, promoted angiogenesis and improved ovarian function in POF rats by activating VEGF/VEGFR-2/FAK pathway. Moreover, YJD improved the intrauterine microenvironment for implantation in POF rats, thereby improving fertility.

Clinical trial number: Not applicable.

益经汤通过激活VEGF/VEGFR-2/FAK通路改善大鼠卵巢早衰。
背景:卵巢早衰(POF)被定义为发生在40岁之前的闭经,此时卵巢功能减弱甚至衰竭。这种疾病严重影响妇女未来的健康和生育能力。方法:利用基于网络的药理学相关数据库预测益经汤和POF的潜在靶点。采用雷公藤甲素建立POF大鼠模型和人卵巢颗粒细胞损伤模型。采用阴道涂片法监测大鼠的发情周期,并用HE染色法对卵巢组织形态进行染色。采用免疫组织化学、qRT-PCR和Western blotting检测生殖和血管生成相关因子的水平。采用酶联免疫吸附法测定各组性激素水平和氧化应激指标。结果:经YJD治疗后,雷公藤甲素所致卵巢功能异常,恢复正常的发情周期,维持接近正常的卵巢大小,减少卵泡闭锁,增加血管化。此外,YJD治疗使血清P、E2、FSH、LH、AMH、MDA和SOD水平正常化,同时激活VEGF/VEGFR-2/FAK通路。然而,VEGF/VEGFR-2/FAK途径抑制剂逆转了YJD在POF大鼠中表现出的这些药理作用。此外,YJD增加了POF大鼠的妊娠率和活产数。结论:YJD通过激活VEGF/VEGFR-2/FAK通路,降低POF大鼠氧化应激水平,促进血管生成,改善卵巢功能。此外,YJD改善了POF大鼠的宫内植入微环境,从而提高了生育能力。临床试验号:不适用。
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来源期刊
Journal of Ovarian Research
Journal of Ovarian Research REPRODUCTIVE BIOLOGY-
CiteScore
6.20
自引率
2.50%
发文量
125
审稿时长
>12 weeks
期刊介绍: Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ. Topical areas include, but are not restricted to: Ovary development, hormone secretion and regulation Follicle growth and ovulation Infertility and Polycystic ovarian syndrome Regulation of pituitary and other biological functions by ovarian hormones Ovarian cancer, its prevention, diagnosis and treatment Drug development and screening Role of stem cells in ovary development and function.
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