富氢水治疗以 RT1-Db1 和 RT1-Bb 为靶点，缓解大鼠卵巢早衰。

Hydrogen-rich water treatment targets RT1-Db1 and RT1-Bb to alleviate premature ovarian failure in rats.

机构信息

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin, China.

出版信息

PeerJ. 2023 Jun 28;11:e15564. doi: 10.7717/peerj.15564. eCollection 2023.

DOI:10.7717/peerj.15564

PMID:37397014

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10314742/

Abstract

BACKGROUND

Premature ovarian failure (POF) is defined as the cessation of ovarian function before the age of 40 years, imposing a significant health burden on patients. However, effective etiological therapy for POF is scarce. Thus, we aimed to explore the protective role and targets of hydrogen-rich water (HRW) in POF.

METHODS

Based on cyclophosphamide (CTX)-induced POF rat models, the protective role of HRW treatment was mainly determined through serum 17--estradiol (E2), follicle-stimulating hormone (FSH), anti-mullerian hormone (AMH) levels, ovarian histomorphological analysis, and TUNEL assay. Tandem mass tag (TMT)-based quantitative proteomic analysis was then conducted on ovarian tissues, and the targets of HRW in POF were identified integrating differential expression analysis, functional enrichment analysis, and interaction analysis.

RESULTS

In HRW treatment of POF rats, the serum AMH and E2 levels significantly increased, and FSH level significantly reduced, indicating the protective role of HRW. After TMT quantitative proteomic analysis, a total of 16 candidate differentially expressed proteins (DEPs) were identified after the cross analysis of DEPs from POF vs. control and POF+HRW vs. POF groups, which were found to be significantly enriched in 296 GO terms and 36 KEGG pathways. The crucial targets, RT1-Db1 and RT1-Bb, were finally identified based on both protein-protein interaction network and GeneMANIA network.

CONCLUSIONS

The HRW treatment could significantly alleviate the ovarian injury of POF rats; RT1-Db1 and RT1-Bb are identified as two crucial targets of HRW treatment in POF rats.

摘要

背景

卵巢早衰（POF）是指 40 岁以前卵巢功能衰竭，给患者带来了沉重的健康负担。然而，POF 的有效病因治疗方法却很少。因此，我们旨在探讨富氢水（HRW）在 POF 中的保护作用和靶点。

方法

基于环磷酰胺（CTX）诱导的 POF 大鼠模型，主要通过血清 17-β雌二醇（E2）、卵泡刺激素（FSH）、抗苗勒管激素（AMH）水平、卵巢组织形态学分析和 TUNEL 检测来确定 HRW 治疗的保护作用。然后对卵巢组织进行串联质量标签（TMT）定量蛋白质组学分析，并通过差异表达分析、功能富集分析和相互作用分析，确定 HRW 在 POF 中的靶点。

结果

在 POF 大鼠的 HRW 治疗中，血清 AMH 和 E2 水平显著升高，FSH 水平显著降低，表明 HRW 具有保护作用。经过 TMT 定量蛋白质组学分析，在 POF 与对照组和 POF+HRW 与 POF 组的差异表达蛋白（DEPs）交叉分析后，共鉴定出 16 个候选 DEP，这些 DEP 显著富集在 296 个 GO 术语和 36 个 KEGG 途径中。最后，基于蛋白质-蛋白质相互作用网络和 GeneMANIA 网络，确定了关键靶点 RT1-Db1 和 RT1-Bb。