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基于准靶向代谢组学的高原肺水肿生物标志物初步筛选

Preliminary screening of biomarkers in HAPE based on quasi-targeted metabolomics.

作者信息

Lin Xue, Dai Chongyang, Chen Zhi, Zhang Tongzuo, Pu Xiaoyan

机构信息

Department of Basic Medicine, Medical College of Qinghai University, Xining, Qinghai Province, China.

West China Hospital, Sichuan University, Chengdu, Sichuan Provience, China.

出版信息

Front Physiol. 2023 Mar 9;14:1122026. doi: 10.3389/fphys.2023.1122026. eCollection 2023.

Abstract

High altitude pulmonary edema (HAPE) is a serious threat to the physical and mental health of people who quickly enter high plateaus, deserves more attention and in-depth research. In our study, through the detection of various physiological indexes and other phenotypes in a HAPE rat model, the HAPE group showed a significant decrease in oxygen partial pressure and oxygen saturation, and a significant increase in pulmonary artery pressure and lung tissue water content. The lung histomorphology showed characteristics such as pulmonary interstitial thickening and inflammatory cell infiltration. We applied quasi-targeted metabolomics to compare and analyze the components of metabolites in arterial-veinous blood in control rats and HAPE rats. Using kyoto Encyclopedia of Genes Genomes (KEGG) enrichment analysis and two machine algorithms, we speculate that after hypoxic stress and comparing arterial blood and venous blood products in rats, the metabolites were richer, indicating that normal physiological activities, such as metabolism and pulmonary circulationhad a greater impact after hypoxic stress; D-mannose, oxidized glutathione, glutathione disulfide, and dehydrocholic acid in arterial blood play key roles in predicting the occurrence of HAPE; in venous blood, L-leucine, L-thyroxine, and cis-4-hydroxy- D-proline may have key roles, which can be considered biomarkers of HAPE. This result provides a new perspective for the further diagnosis and treatment of plateau disease and lays a strong foundation for further research.

摘要

高原肺水肿(HAPE)对快速进入高海拔地区人群的身心健康构成严重威胁,值得更多关注和深入研究。在我们的研究中,通过检测HAPE大鼠模型中的各种生理指标和其他表型,HAPE组的氧分压和氧饱和度显著降低,肺动脉压和肺组织含水量显著升高。肺组织形态学表现为肺间质增厚和炎性细胞浸润等特征。我们应用准靶向代谢组学对对照大鼠和HAPE大鼠动静脉血中的代谢物成分进行比较分析。利用京都基因与基因组百科全书(KEGG)富集分析和两种机器学习算法,我们推测在低氧应激后,比较大鼠的动脉血和静脉血产物,代谢物更丰富,表明低氧应激后代谢和肺循环等正常生理活动受到更大影响;动脉血中的D-甘露糖、氧化型谷胱甘肽、谷胱甘肽二硫化物和脱氢胆酸在预测HAPE的发生中起关键作用;在静脉血中,L-亮氨酸、L-甲状腺素和顺式-4-羟基-D-脯氨酸可能起关键作用,可被视为HAPE的生物标志物。这一结果为高原病的进一步诊断和治疗提供了新的视角,为进一步研究奠定了坚实基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4380/10034721/5c1ace75f473/fphys-14-1122026-g001.jpg

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