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昆泰胶囊通过 PI3K/AKT/mTOR 通路减轻卵巢早衰。

Kuntai capsule attenuates premature ovarian failure through the 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.

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

出版信息

J Ethnopharmacol. 2019 Jul 15;239:111885. doi: 10.1016/j.jep.2019.111885. Epub 2019 Apr 19.

DOI:10.1016/j.jep.2019.111885
PMID:31009706
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Kuntai capsule (KTC), a type of herb formulas, was first described in the book of Shang Han Za Bing Lun in the third century. KTC has been widely used for the clinical treatment of menopausal syndrome. Considering that premature ovarian failure is also known as premature menopause, this study was designed to investigate the effects and mechanisms of KTC on a mouse model of premature ovarian failure.

MATERIALS AND METHODS

Forty-five female C57BL/6 mice were chosen for this study. Fifteen of the mice were separated into the Control group. The remaining thirty were used to establish the premature ovarian failure model by injecting intraperitoneally with 75 mg/kg cyclophosphamide and then by randomly dividing the mice into two groups. One group was considered the Model group, the other group treated with the Kuntai capsule intragastrically every day for one week called the KTC group. After treatment, mice were sacrificed for sampling. The ovaries morphology of mice was observed by hematoxylin and eosin (HE) staining, and all follicles were counted under microscope. Western blotting was used to detect the PI3K/AKT/mTOR pathway activation. 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.

RESULTS

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

CONCLUSIONS

The KTC showed protective potentials of ovarian reserve and fertility to attenuate premature ovarian failure, which was relatively associated with activation of the PI3K/AKT/mTOR signaling pathway.

摘要

民族药理学相关性

昆泰胶囊(KTC)是一种草药方剂,最早在公元三世纪的《伤寒杂病论》中描述。KTC 已广泛用于治疗更年期综合征的临床治疗。考虑到卵巢早衰也称为早发性绝经,因此本研究旨在研究 KTC 对卵巢早衰小鼠模型的作用和机制。

材料和方法

本研究选择了 45 只雌性 C57BL/6 小鼠。其中 15 只被分离到对照组。其余 30 只用于通过腹腔注射 75mg/kg 环磷酰胺建立卵巢早衰模型,然后将小鼠随机分为两组。一组被认为是模型组,另一组用昆泰胶囊每天灌胃治疗一周,称为 KTC 组。治疗后,处死小鼠进行采样。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。Western blot 用于检测 PI3K/AKT/mTOR 通路的激活。通过酶联免疫吸附试验(ELISA)测量血清卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E)和抗苗勒管激素(AMH)水平。通过给治疗后的小鼠 8 周繁殖来观察生育能力。

结果

我们发现 KTC 组的原始卵泡计数比模型组增加。与模型组相比,KTC 组的 PI3K、AKT、mTOR、4E-BP1 和 S6K 磷酸化显著降低。与模型组相比,KTC 组的血清 FSH 和 LH 水平降低,而血清 E 和 AMH 水平升高。与模型组相比,KTC 组的产仔数增加。

结论

KTC 对卵巢储备和生育能力表现出保护潜力,可减轻卵巢早衰,这与激活 PI3K/AKT/mTOR 信号通路有关。

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