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基于系统药理学探讨枸杞女贞六合汤对早发性卵巢功能不全PI3K/mTOR信号通路的影响

Exploring the effect of Gouqi Nuzhen Liuhe decoction on the PI3K/mTOR signaling pathway for premature ovarian insufficiency based on system pharmacology.

作者信息

Yang Kailin, Wu Lingyu, Zeng Liuting, Xiang Wang, Chen Junpeng, Yan Yexing, Hao Moujia, Song Tian, Zhai Enjian, Zhang Guomin, Liu Huiping

机构信息

Hunan Provincial Key Laboratory of Translational Medicine for Traditional Chinese Medicine Prescription Research, Hunan University of Chinese Medicine, Changsha, Hunan Province, China.

Psychosomatic Laboratory, Department of Psychiatry, Daqing Hospital of Traditional Chinese Medicine, China.

出版信息

Heliyon. 2024 Jun 14;10(12):e33105. doi: 10.1016/j.heliyon.2024.e33105. eCollection 2024 Jun 30.

Abstract

OBJECTIVE

To explore the effect of Gouqi Nuzhen Liuhe Decoction (GNLHD) on the PI3K/mTOR Signaling Pathway for Premature Ovarian Insufficiency (POI) based on system pharmacology.

METHODS

First, the system pharmacology approach was used to predict the mechanism of GNLHD. Then, mice were randomly divided into model group, positive group, GNLHD high-dose group, GNLHD medium-dose group, and GNLHD low-dose group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of ovarian tissue under light microscope. The expression levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by enzyme-linked immunosorbent assay. The expressions of PI3K, AKT1 and mTOR proteins in ovarian tissue were detected by immunohistochemistry.

RESULTS

The results of system pharmacology showed that GNLHD may regulate biological processes and signaling pathways such as: reproductive structure development, reproductive system development, Oocyte meiosis and so on. Compared with the model group, the levels of E2 in the GNLHD group were increased, and the levels of FSH and LH were decreased (P < 0.05). Compared with the model group, the number of mature follicles in the GNLHD group was significantly increased, the number of atretic follicles was relatively decreased, and the expressions of PI3K, AKT1, and MTOR proteins in the GNLHD group were significantly increased (P < 0.05).

CONCLUSION

GNLHD may improve the ovarian function of POI mice by affecting the expression of PI3K, AKT1 and mTOR proteins, promote the growth and development of follicles, increase the E2 level, reduce FSH and LH level, and maintain the stability of the ovarian internal environment.

摘要

目的

基于系统药理学探讨枸杞女贞六合汤(GNLHD)对卵巢早衰(POI)PI3K/mTOR信号通路的影响。

方法

首先,采用系统药理学方法预测GNLHD的作用机制。然后,将小鼠随机分为模型组、阳性组、GNLHD高剂量组、GNLHD中剂量组和GNLHD低剂量组。采用苏木精-伊红(HE)染色在光镜下观察卵巢组织的病理变化。采用酶联免疫吸附测定法检测雌二醇(E2)、卵泡刺激素(FSH)和黄体生成素(LH)的表达水平。采用免疫组织化学法检测卵巢组织中PI3K、AKT1和mTOR蛋白的表达。

结果

系统药理学结果显示,GNLHD可能调节生殖结构发育、生殖系统发育、卵母细胞减数分裂等生物过程和信号通路。与模型组比较,GNLHD组E2水平升高,FSH和LH水平降低(P<0.05)。与模型组比较,GNLHD组成熟卵泡数量显著增加,闭锁卵泡数量相对减少,GNLHD组PI3K、AKT1和MTOR蛋白表达显著增加(P<0.05)。

结论

GNLHD可能通过影响PI3K、AKT1和mTOR蛋白表达改善POI小鼠卵巢功能,促进卵泡生长发育,提高E2水平,降低FSH和LH水平,维持卵巢内环境稳定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8190/11238132/3d75bd93de95/gr1.jpg

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