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东方田鼠对日本血吸虫感染内在抗性机制的代谢组学分析

Metabolomic analysis of the intrinsic resistance mechanisms of Microtus fortis against Schistosoma japonicum infection.

作者信息

He Tianqiong, Zhang Du, Wen Yixin, Liu Qian, Zhou Junkang, Zhi Wenling, OuYang Lingxuan, Qi Yushan, Zhou Zikang, Gao Xin, Li Fan, Su Zhijie, Shen Jia, Zhou Zhijun

机构信息

Department of Laboratory Animal Science, Xiangya Medical College, Changsha, 410013, Hunan, China.

Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, 410013, Hunan, China.

出版信息

Sci Rep. 2025 Feb 28;15(1):7147. doi: 10.1038/s41598-025-91164-z.

Abstract

Microtus fortis (M. fortis) is the only mammal known in China that is intrinsically resistant to Schistosoma japonicum (S. japonicum) infection. Nevertheless, the underlying resistance mechanism of M. fortis against schistosomes are still unclear. In this study, we detected and compared colon aqueous extracts and serum metabolic profiles between M. fortis and ICR mice before and after S. japonicum infection using liquid chromatography-mass spectrometry (LC-MS). We identified 232 specific colon aqueous extract metabolites and 79 specific serum metabolites of M. fortis infected with or without S. japonicum at two weeks compared with those of ICR mice, which might be closely correlated with the time-course of schistosomiasis progression and could also be used as indicators for the M. fortis against S. japonicum, for example, nonadecanoic acid, hesperetin, glycocholic acid, 2-Aminobenzoic acid, 6-hydroxydaidzein and spermidine. And the enriched pathways were further identified, our findings revealed that S. japonicum infection induced the metabolic changes involved in a variety of metabolic pathways including amino acid metabolism, lipid metabolism, ABC transporters, central carbon metabolism in cancer and bile secretion. These results indicated that the colon aqueous extracts and serum metabolic profiles were significantly different between M. fortis and ICR mice before and after S. japonicum infection and will provide new insights into the underlying resistance mechanism of M. fortis against S. japonicum infection and identify promising candidates for the use of drugs against schistosomes.

摘要

东方田鼠是中国已知的唯一一种对日本血吸虫感染具有内在抗性的哺乳动物。然而,东方田鼠对血吸虫的潜在抗性机制仍不清楚。在本研究中,我们使用液相色谱-质谱联用技术(LC-MS)检测并比较了日本血吸虫感染前后东方田鼠和ICR小鼠的结肠水提取物和血清代谢谱。与ICR小鼠相比,我们鉴定出了感染或未感染日本血吸虫两周的东方田鼠的232种特异性结肠水提取物代谢物和79种特异性血清代谢物,这些代谢物可能与血吸虫病进展的时间进程密切相关,也可作为东方田鼠抗日本血吸虫的指标,例如十九烷酸、橙皮素、甘氨胆酸、2-氨基苯甲酸、6-羟基大豆苷元和亚精胺。进一步鉴定了富集途径,我们的研究结果表明,日本血吸虫感染诱导了多种代谢途径的代谢变化,包括氨基酸代谢、脂质代谢、ABC转运蛋白、癌症中的中心碳代谢和胆汁分泌。这些结果表明,日本血吸虫感染前后东方田鼠和ICR小鼠的结肠水提取物和血清代谢谱存在显著差异,这将为东方田鼠抗日本血吸虫感染的潜在抗性机制提供新的见解,并为抗血吸虫药物的使用鉴定出有前景的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a620/11871335/39510e02e20f/41598_2025_91164_Fig1_HTML.jpg

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