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电针对小鼠卵巢早衰的作用机制可能与调控 PI3K/AKT/mTOR 信号通路有关。

Electro-acupuncture attenuates the mice premature ovarian failure via mediating PI3K/AKT/mTOR pathway.

机构信息

Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, China; First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China.

College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China.

出版信息

Life Sci. 2019 Jan 15;217:169-175. doi: 10.1016/j.lfs.2018.11.059. Epub 2018 Dec 3.

Abstract

AIMS

Electro-acupuncture (EA) is frequently recommended as a complementary therapy for premature ovarian failure (POF) in the clinical. However, little information exists about its potential treatment mechanisms. The study was designed to observe the effect of EA to ovarian function and fertility in POF mice model, and investigated its potential mechanisms on PI3K/AKT/mTOR signaling pathway.

MATERIALS AND METHODS

Forty-five female C57/BL6 mice were divided into the Control, the Model and the EA group. The ovaries morphology of mice was observed by hematoxylin and eosin (HE) staining, and all follicles were counted under microscope. The protein expression of PI3K, phospho-PI3K, AKT, phospho-AKT, mTOR, phospho-mTOR, S6, phospho-S6, 4E-BP1 and phospho-4E-BP1 were detected by western blotting. The data was presented as the ratio of phosphorylation protein to total protein. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E) and anti-Mullerian hormone (AMH) levels were measured by enzyme-linked immunosorbent assay (ELISA). The fertility was observed by giving treated mice 8 weeks for breeding.

KEY FINDINGS

We found that primordial follicle counts were increased in EA group compared to Model group. The phosphorylation of PI3K, AKT, mTOR, 4E-BP1 and S6K in EA group significantly reduced compared to Model group. Serum FSH and LH levels in EA group were decreased compared to Model group, while, serum E and AMH levels in EA group were increased compared with Model group. The litter size in EA group was improved compared to Model group.

SIGNIFICANCE

The effects of EA on the PI3K/AKT/mTOR signaling pathway may represent one of the mechanisms involved in attenuating the mice POF.

摘要

目的

电针(EA)常被推荐为治疗卵巢早衰(POF)的一种辅助疗法。然而,关于其潜在治疗机制的信息很少。本研究旨在观察 EA 对 POF 小鼠模型卵巢功能和生育能力的影响,并研究其对 PI3K/AKT/mTOR 信号通路的潜在机制。

材料和方法

将 45 只雌性 C57/BL6 小鼠分为对照组、模型组和 EA 组。通过苏木精和伊红(HE)染色观察小鼠卵巢形态,在显微镜下计数所有卵泡。通过 Western blot 检测 PI3K、磷酸化 PI3K、AKT、磷酸化 AKT、mTOR、磷酸化 mTOR、S6、磷酸化 S6、4E-BP1 和磷酸化 4E-BP1 的蛋白表达。数据表示为磷酸化蛋白与总蛋白的比值。通过酶联免疫吸附试验(ELISA)测定血清卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E)和抗苗勒管激素(AMH)水平。通过 8 周的繁殖给予治疗小鼠,观察其生育能力。

主要发现

与模型组相比,EA 组原始卵泡计数增加。与模型组相比,EA 组 PI3K、AKT、mTOR、4E-BP1 和 S6K 的磷酸化显著降低。与模型组相比,EA 组血清 FSH 和 LH 水平降低,而血清 E 和 AMH 水平升高。与模型组相比,EA 组的产仔数增加。

意义

EA 对 PI3K/AKT/mTOR 信号通路的影响可能是其减轻小鼠 POF 的机制之一。

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