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腹腔注射白消安对精原干细胞代谢特征的影响OACSTPCD

Effects of intraperitoneal injection of busulfan on metabolic characteristics of spermatogonial stem cells

中文摘要英文摘要

目的 通过构建白消安处理的小鼠模型,探讨其对小鼠睾丸精原干细胞(SSCs)代谢的影响.方法 采用8 周龄C57BL/6J雄性小鼠,腹腔注射 10 mg/kg白消安,于第 0 天、第 5 天和第 10 天取材,并通过免疫磁珠法分选出Thy1 阳性细胞.随后对这些细胞进行了纯度鉴定和代谢组学分析.结果 实验发现白消安处理能明显降低小鼠睾丸质量(P<0.05),并损伤睾丸的组织结构.基于主成分分析(PCA)和偏最小二乘法判别分析(PLS-DA)模型显示,处理 0d、5d和 10d的样本组间存在显著的代谢差异.共筛选鉴定出 89 种差异代谢物,包括谷胱甘肽(GSH)、牛磺酸、精氨酸、必需氨基酸(EAAs)和不饱和脂肪酸(UFAs)等,其重要相关代谢途径涉及甘油磷脂代谢、精氨酸和脯氨酸代谢等.结论 白消安通过影响特定的代谢途径,产生明显的生殖毒性效应,导致小鼠睾丸质量下降和组织结构损伤.代谢组学分析其潜在的生殖毒性机制可能与脂质代谢、精氨酸和脯氨酸代谢等代谢通路有关.

Objective To establish a mouse model treated with busulfan and to investigate its effects on the metabo-lism of spermatogonial stem cells(SSCs)of mouse testis.Methods C57BL/6J male mice with age of 8 weeks were injected with 10 mg/kg of busulfan intraperitoneally,then Thy1 positive cells were selected by immunomagnetic beads on day 0,day 5 and day 10 and followed by identification for purity and metabolomic analysis.Results The testis weight ratio decreased and the tissue structure of testis was damaged(P<0.05).Based on the results of principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA),there were signifi-cant metabolic differences between the sample groups treated for 0 d,5 d and 10 d.A total of 89 differential metabolites were identified including glutathione(GSH),arginine and unsaturatedfatty acids(UFAs),and their important metabolic pathways involved glycerophospholipid metabolism,arginine and proline metabolism.Conclu-sions Affecting the specific metabolic pathway may result in obvious reproductive toxicity and lead to decrease of testicular weight as well as tissue structure damage in mice.Metabolomic analysis showed that the potential repro-ductive toxicity mechanism of SSCs may be related to the metabolic pathways such as lipid metabolism,arginine and proline metabolism.

余志鑫;邙新雨;邹定峰;缪时英;宋伟;李凯

中国医学科学院基础医学研究所 北京协和医学院基础学院 生物化学与分子生物学系重大疾病共性机制研究全国重点实验室,北京 100005

基础医学

白消安生殖毒性代谢组学精原干细胞

busulfanreproductive toxicitymetabolomicsspermatogonial stem cells

《基础医学与临床》 2024 (006)

793-799 / 7

国家自然科学基金(92268111,32370910)

10.16352/j.issn.1001-6325.2024.06.0793

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