干细胞外泌体介导线粒体与脂肪酸代谢修复肝细胞损伤的作用机制OA
Mechanism of stem cell exosome-mediated repair of hepatocyte in-jury via mitochondrial and fatty acid metabolism
目的:探究脐带间充质干细胞外泌体修复四氯化碳(CCl4)诱导急性肝损伤的代谢机制,分析关键代谢物在调控修复中的作用.方法:实验分为 CCl4 组、CCl4+外泌体低剂量组和 CCl4+外泌体高剂量组,检测各组 HL-7702的细胞活力,谷草转氨酶(AST)、谷丙转氨酶(ALT)和丙二醛(MDA)的水平,靶向代谢组学分析 CCl4 组和CCl4+外泌体组的差异代谢物,激光共聚焦显微镜观察 HL7702细胞核和线粒体与外泌体的共定位关系,透射电镜观察各组细胞的线粒体结构变化.结果:外泌体在 CCl4 浓度为 25 mmol/L 时显著逆转了细胞活性下降趋势,外泌体显著降低细胞 AST、ALT 和 MDA 水平,CCl4 组和 CCl4+外泌体组共存在73种显著差异代谢物,其中包括甘氨脱氧胆酸与十四烷二酸.荧光染色后观察到外泌体与细胞核及线粒体的共定位现象.结论:外泌体显著逆转了 CCl4 诱导的 HL-7702细胞 AST、ALT和 MDA 水平异常,并保护线粒体结构和氧化应激损伤.代谢组学结果表明外泌体可能通过介导线粒体与脂肪酸代谢修复肝细胞损伤.
AIM:To investigate the metabolic mechanism by which umbilical cord mesenchymal stem cell exosomes repair CCl4-induced acute liver injury and to analyze the role of key metabolites in regulating the repair process.METHODS:The ex-periment was divided into three groups:the CCl4 group,the CCl4+low-dose exosome group,and the CCl4+high-dose exosome group.Cell viability of HL-7702 cells,as well as levels of AST,ALT,and MDA,were measured.Targeted metabolomics analysis was performed to identify differential metabolites between the CCl4 group and the CCl4+exosome group.The co-localization relationship between ex-osomes and the nucleus or mitochondria in HL-7702 cells was observed using confocal laser scanning mi-croscopy.Mitochondrial structural changes in each group were examined by transmission electron mi-croscopy.RESULTS:Exosomes significantly re-versed the decline in cell viability induced by 25 mmol/L CCl4.Additionally,exosomes markedly re-duced AST,ALT,and MDA levels.A total of 73 signif-icantly differential metabolites were identified be-tween the CCl4 group and the CCl4+exosome group,including glycodeoxycholic acid and tetradecane-dioic acid.Fluorescence staining revealed co-local-ization of exosomes with both the nucleus and mi-tochondria.CONCLUSION:Exosomes significantly reversed the abnormal levels of AST,ALT,and MDA induced by CCl4 in HL-7702 cells and protected mi-tochondrial structure against oxidative stress dam-age.Metabolomic findings suggest that exosomes may repair hepatocyte injury by mediating mito-chondrial function and fatty acid metabolism.
尹新新;谢昌鹏;李雪静;张丽萍;苏占海;王海燕;吴穹;潘元明;安娟
青海大学医学院基础医学部,西宁 810016,青海青海大学医学院基础医学部,西宁 810016,青海青海大学医学院基础医学部,西宁 810016,青海青海大学医学院基础医学部,西宁 810016,青海青海大学医学院基础医学部,西宁 810016,青海青海大学医学院基础医学部,西宁 810016,青海青海大学医学院基础医学部,西宁 810016,青海首都医科大学北京胸科医院肿瘤研究中心,北京 101149青海大学医学院基础医学部,西宁 810016,青海
医药卫生
肝损伤外泌体线粒体脂肪酸代谢代谢组学
liver injuryexosomesmitochondriafatty acid metabolismmetabonomics
《中国临床药理学与治疗学》 2026 (9)
1162-1172,11
国家自然科学基金(82260846)青海省科技厅应用基础研究项目(2023-ZJ-754)2023年度青海省昆仑英才-领军人才项目
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