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区分小鼠模型中心肌梗死与绞杀死亡的氨基酸代谢组学特征。

The amino acid metabolomics signature of differentiating myocardial infarction from strangulation death in mice models.

机构信息

College of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, No. 361 Zhongshan East Road, Chang'an District, Shijiazhuang, 050017, Hebei, China.

Forensic Pathology Lab, Guangdong Public Security Department, Guangzhou, China.

出版信息

Sci Rep. 2023 Sep 11;13(1):14999. doi: 10.1038/s41598-023-41819-6.

DOI:10.1038/s41598-023-41819-6
PMID:37696922
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10495377/
Abstract

This study differentiates myocardial infarction (MI) and strangulation death (STR) from the perspective of amino acid metabolism. In this study, MI mice model via subcutaneous injection of isoproterenol and STR mice model by neck strangulation were constructed, and were randomly divided into control (CON), STR, mild MI (MMI), and severe MI (SMI) groups. The metabolomics profiles were obtained by liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics. Principal component analysis, partial least squares-discriminant analysis, volcano plots, and heatmap were used for discrepancy metabolomics analysis. Pathway enrichment analysis was performed and the expression of proteins related to metabolomics was detected using immunohistochemical and western blot methods. Differential metabolites and metabolite pathways were screened. In addition, we found the expression of PPM1K was significantly reduced in the MI group, but the expression of p-mTOR and p-S6K1 were significantly increased (all P < 0.05), especially in the SMI group (P < 0.01). The expression of Cyt-C was significantly increased in each group compared with the CON group, especially in the STR group (all P < 0.01), and the expression of AMPKα1 was significantly increased in the STR group (all P < 0.01). Our study for the first time revealed significant differences in amino acid metabolism between STR and MI.

摘要

本研究从氨基酸代谢的角度区分心肌梗死(MI)和绞杀死亡(STR)。在这项研究中,通过皮下注射异丙肾上腺素构建 MI 小鼠模型,通过颈部绞杀构建 STR 小鼠模型,并将其随机分为对照(CON)、STR、轻度 MI(MMI)和重度 MI(SMI)组。采用基于液相色谱-质谱(LC-MS)的非靶向代谢组学获得代谢组学图谱。采用主成分分析、偏最小二乘判别分析、火山图和热图进行差异代谢组学分析。进行通路富集分析,并使用免疫组织化学和 Western blot 方法检测与代谢组学相关的蛋白质的表达。筛选差异代谢物和代谢途径。此外,我们发现 MI 组中 PPM1K 的表达显著降低,但 p-mTOR 和 p-S6K1 的表达显著增加(均 P<0.05),尤其是在 SMI 组(P<0.01)。与 CON 组相比,每个组的 Cyt-C 表达均显著增加,尤其是在 STR 组(均 P<0.01),并且在 STR 组中 AMPKα1 的表达显著增加(均 P<0.01)。本研究首次揭示了 STR 和 MI 之间氨基酸代谢的显著差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/c97dff5edef0/41598_2023_41819_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/baa9eef2ff01/41598_2023_41819_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/026113f740ba/41598_2023_41819_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/5be403e9729c/41598_2023_41819_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/f888685abab8/41598_2023_41819_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/13af86097c90/41598_2023_41819_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/c97dff5edef0/41598_2023_41819_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/baa9eef2ff01/41598_2023_41819_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/026113f740ba/41598_2023_41819_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/5be403e9729c/41598_2023_41819_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/f888685abab8/41598_2023_41819_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/13af86097c90/41598_2023_41819_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/10495377/c97dff5edef0/41598_2023_41819_Fig6_HTML.jpg

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Bradykinin postconditioning protects rat hippocampal neurons after restoration of spontaneous circulation following cardiac arrest via activation of the AMPK/mTOR signaling pathway.缓激肽后处理通过激活AMPK/mTOR信号通路,在心脏骤停后自主循环恢复时保护大鼠海马神经元。
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