|
| 环磷酰胺致大鼠弱精症的代谢组学特征 |
| Metabolomic Characteristics of Cyclophosphamide Induced Asthenospermia in Rats |
| 投稿时间：2024-09-21 修订日期：2024-09-21 |
| DOI： |
| 中文关键词: 弱精症 代谢组学 氧化应激 环磷酰胺 活性氧 |
| 英文关键词: Asthenospermia Metabolomics Oxidative Stress Cyclophosphamide Reactive Oxygen Species |
| 基金项目:福建省自然科学基金（2020J05281）；福建省妇幼保健院科技创新启动基金（妇幼YCXY21-06） |
|
| 摘要点击次数: 0 |
| 全文下载次数: 0 |
| 中文摘要: |
| 目的：观察环磷酰胺致大鼠弱精症模型（CP）与正常组大鼠的代谢差异，探索其潜在的代谢特征及通路机制。方法：用环磷酰胺（30 mg/kg)连续腹腔注射7天，建立大鼠弱精症模型；通过精子计数来检测精子浓度和活力；采用HE染色观察睾丸形态；采用液相色谱-质谱联用（LC-MS）非靶向代谢组学检测两组间的代谢差异。采用试剂盒检测血清中超氧化物歧化酶（SOD）、脂质氧化酶（MDA）、总谷胱甘肽的浓度。 结果: 精子计数结果显示，与正常组相比，环磷酰胺组的精子浓度降低，精子活力下降。HE染色结果表明，环磷酰胺组的各级生精细胞排列紊乱，数量较正常组显著减少。提示弱精症大鼠模型建立成功。代谢组学分析结果显示两组代谢轮廓分离趋势较好，共筛选出129种差异代谢物。对差异代谢物进行KEGG通路富集分析，结果显示胆碱代谢、甘油磷脂代谢及鞘脂信号通路等代谢通路在两组间具有显著意义。KEGG鞘脂信号通路图显示活性氧（ROS）参与了该信号通路调控。弱精组中血清SOD和总谷胱甘肽浓度下降，MDA浓度增高，差异具有统计学意义。结论：弱精症的发生可能与其抗氧化水平下降，脂质氧化水平升高有关，过度的氧化应激可能破坏精子膜结构的完整性，对精子DNA造成一定的损伤，从而降低精子的数量和活力，其机制与鞘脂代谢通路密切相关。 |
| 英文摘要: |
| Objective: To observe the metabolic differences between the rat model of control and cyclophosphamide (CP) induced asthenospermia groups, and to explore its potential metabolic characteristics and pathway mechanisms. Methods: The rat model of asthenospermia was established through continuous intraperitoneal injections of cyclophosphamide (30 mg/kg) over a period of 7 days. Sperm concentration and motility were assessed via sperm count analysis. Testicular morphology was examined using hematoxylin-eosin (HE) staining. The metabolic differences between CP induced asthenospermia and control groups were analyzed using liquid chromatography-mass spectrometry (LC-MS) based on non-targeted metabolomics. The concentrations of superoxide dismutase (SOD), malondialdehyde (MDA), and total glutathione in serum were quantified employing specific reagent kits. Results: The sperm count results demonstrated a significantly reduction in both sperm concentration and motility in the CP group compared to the control group. The results in HE staining revealed disorganized arrangement and a significant decrease in the number of spermatogenic cells at all stages in the CP group relative to the control group. These findings indicate that a rat model of asthenospermia was successfully established. Metabolomic analysis disclosed distinct metabolic profiles between the two groups, identifying 129 differential metabolites. KEGG pathway enrichment analysis of these differential metabolites indicated significant alterations in choline metabolism, glycerophospholipid metabolism, and sphingolipid signaling pathways. Furthermore, the KEGG sphingolipid signaling pathway diagram demonstrated the involvement of reactive oxygen species (ROS) in the regulation of this signaling pathway. The concentrations of SOD and total glutathione exhibited a significant reduction, while the concentration of MDA demonstrated a statistically significant increase in serum. Conclusions: The incidence of asthenospermia may be associated with a reduction in antioxidant levels and an elevation in lipid oxidation levels. Excessive oxidative stress can compromise the integrity of the sperm membrane structure and induce damage to sperm DNA, consequently diminishing sperm count and motility. The underlying mechanism was intricately linked to the sphingolipid metabolic pathway. |
|
View Fulltext
查看/发表评论 下载PDF阅读器 |
| 关闭 |
