中药自噬驱动的脂质调节可减轻重症急性胰腺炎的心脏脂肪毒性。

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-08-11 eCollection Date: 2025-01-01 DOI:10.7150/thno.117243
Yue Yang, Qian Hu, Hongxin Kang, Long Xie, Yue Hu, Juan Li, Xianlin Zhao, Lv Zhu, Wenfu Tang, Jingping Liu, Christopher J Lyon, Meihua Wan
{"title":"中药自噬驱动的脂质调节可减轻重症急性胰腺炎的心脏脂肪毒性。","authors":"Yue Yang, Qian Hu, Hongxin Kang, Long Xie, Yue Hu, Juan Li, Xianlin Zhao, Lv Zhu, Wenfu Tang, Jingping Liu, Christopher J Lyon, Meihua Wan","doi":"10.7150/thno.117243","DOIUrl":null,"url":null,"abstract":"<p><p><b>Rationale:</b> Myocardial injury is a common and life-threatening complication of severe acute pancreatitis (SAP) and is driven primarily by metabolic disturbances. This study aimed to elucidate the pathogenesis of SAP-induced cardiac injury (SACI) and to identify effective therapeutic strategies. <b>Methods:</b> Untargeted metabolomics and proteomics analyses were employed to identify metabolic pathways and proteins associated with myocardial injury in SACI mouse model. Histological and Western blot assays were used to assess lipid droplet (LD) accumulation, the expression of autophagy markers, and LD-autophagosome colocalization. The traditional Chinese medicine formula Taohong Siwu Decoction (THSWD) was tested for its therapeutic potential in a SACI mouse model and a SACI cardiomyocyte model established by incubating primary mouse cardiomyocytes with serum from the SACI mouse model. These SACI cardiomyocytes cultures were then treated with serum from control or THSWD-treated mice, with or without autophagy inhibitors, and analyzed for effects on lipophagy, mitochondrial structure and function, long-chain fatty acid metabolism, and oxidative stress. <b>Results:</b> SAP-induced myocardial injury was characterized by disrupted lipid metabolism, leading to abnormal cardiomyocyte LD accumulation and structural and functional deficiencies in their mitochondria. THSWD treatment reduced LD accumulation, restored LD-autophagosome colocalization, and increased mitochondrial structural integrity, membrane potential, and fatty acid β-oxidation. However, these THSWD effects were abolished in the presence of an autophagy inhibitor, implying they occur via a lipophagy-dependent mechanism. <b>Conclusion:</b> Excessive LD accumulation drives mitochondrial dysfunction, contributing to SAP-induced myocardial lipotoxicity. THSWD promotes lipophagy to mitigate lipid accumulation and restore mitochondrial function, and may serve as an effective therapeutic strategy for SAP-induced cardiac metabolic disorders and mitochondrial dysfunction.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8822-8839"},"PeriodicalIF":13.3000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439263/pdf/","citationCount":"0","resultStr":"{\"title\":\"Autophagy-driven lipid regulation by an herbal decoction alleviates cardiac lipotoxicity in severe acute pancreatitis.\",\"authors\":\"Yue Yang, Qian Hu, Hongxin Kang, Long Xie, Yue Hu, Juan Li, Xianlin Zhao, Lv Zhu, Wenfu Tang, Jingping Liu, Christopher J Lyon, Meihua Wan\",\"doi\":\"10.7150/thno.117243\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Rationale:</b> Myocardial injury is a common and life-threatening complication of severe acute pancreatitis (SAP) and is driven primarily by metabolic disturbances. This study aimed to elucidate the pathogenesis of SAP-induced cardiac injury (SACI) and to identify effective therapeutic strategies. <b>Methods:</b> Untargeted metabolomics and proteomics analyses were employed to identify metabolic pathways and proteins associated with myocardial injury in SACI mouse model. Histological and Western blot assays were used to assess lipid droplet (LD) accumulation, the expression of autophagy markers, and LD-autophagosome colocalization. The traditional Chinese medicine formula Taohong Siwu Decoction (THSWD) was tested for its therapeutic potential in a SACI mouse model and a SACI cardiomyocyte model established by incubating primary mouse cardiomyocytes with serum from the SACI mouse model. These SACI cardiomyocytes cultures were then treated with serum from control or THSWD-treated mice, with or without autophagy inhibitors, and analyzed for effects on lipophagy, mitochondrial structure and function, long-chain fatty acid metabolism, and oxidative stress. <b>Results:</b> SAP-induced myocardial injury was characterized by disrupted lipid metabolism, leading to abnormal cardiomyocyte LD accumulation and structural and functional deficiencies in their mitochondria. THSWD treatment reduced LD accumulation, restored LD-autophagosome colocalization, and increased mitochondrial structural integrity, membrane potential, and fatty acid β-oxidation. However, these THSWD effects were abolished in the presence of an autophagy inhibitor, implying they occur via a lipophagy-dependent mechanism. <b>Conclusion:</b> Excessive LD accumulation drives mitochondrial dysfunction, contributing to SAP-induced myocardial lipotoxicity. THSWD promotes lipophagy to mitigate lipid accumulation and restore mitochondrial function, and may serve as an effective therapeutic strategy for SAP-induced cardiac metabolic disorders and mitochondrial dysfunction.</p>\",\"PeriodicalId\":22932,\"journal\":{\"name\":\"Theranostics\",\"volume\":\"15 17\",\"pages\":\"8822-8839\"},\"PeriodicalIF\":13.3000,\"publicationDate\":\"2025-08-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439263/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Theranostics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7150/thno.117243\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Theranostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/thno.117243","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

摘要

理由:心肌损伤是严重急性胰腺炎(SAP)常见且危及生命的并发症,主要由代谢紊乱引起。本研究旨在阐明sap诱导的心脏损伤(SACI)的发病机制,并确定有效的治疗策略。方法:采用非靶向代谢组学和蛋白质组学分析方法,鉴定与SACI小鼠心肌损伤相关的代谢途径和蛋白质。采用组织学和Western blot方法评估脂滴(LD)积累、自噬标志物的表达以及LD-自噬体的共定位。中药桃红四物汤(THSWD)在SACI小鼠模型和SACI小鼠模型血清培养原代小鼠心肌细胞建立的SACI心肌细胞模型中检测其治疗潜力。然后将这些SACI心肌细胞培养物与对照组或经thswd处理的小鼠血清(含或不含自噬抑制剂)一起处理,并分析对脂噬、线粒体结构和功能、长链脂肪酸代谢和氧化应激的影响。结果:sap诱导的心肌损伤以脂质代谢紊乱为特征,导致心肌细胞LD积累异常,线粒体结构和功能缺陷。THSWD处理减少LD积累,恢复LD-自噬体共定位,增加线粒体结构完整性、膜电位和脂肪酸β氧化。然而,这些THSWD效应在自噬抑制剂的存在下被消除,这意味着它们是通过脂噬依赖机制发生的。结论:过量的LD积累导致线粒体功能障碍,参与sap诱导的心肌脂肪毒性。THSWD促进脂质吞噬,减轻脂质积累,恢复线粒体功能,可能是sap诱导的心脏代谢紊乱和线粒体功能障碍的有效治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Autophagy-driven lipid regulation by an herbal decoction alleviates cardiac lipotoxicity in severe acute pancreatitis.

Rationale: Myocardial injury is a common and life-threatening complication of severe acute pancreatitis (SAP) and is driven primarily by metabolic disturbances. This study aimed to elucidate the pathogenesis of SAP-induced cardiac injury (SACI) and to identify effective therapeutic strategies. Methods: Untargeted metabolomics and proteomics analyses were employed to identify metabolic pathways and proteins associated with myocardial injury in SACI mouse model. Histological and Western blot assays were used to assess lipid droplet (LD) accumulation, the expression of autophagy markers, and LD-autophagosome colocalization. The traditional Chinese medicine formula Taohong Siwu Decoction (THSWD) was tested for its therapeutic potential in a SACI mouse model and a SACI cardiomyocyte model established by incubating primary mouse cardiomyocytes with serum from the SACI mouse model. These SACI cardiomyocytes cultures were then treated with serum from control or THSWD-treated mice, with or without autophagy inhibitors, and analyzed for effects on lipophagy, mitochondrial structure and function, long-chain fatty acid metabolism, and oxidative stress. Results: SAP-induced myocardial injury was characterized by disrupted lipid metabolism, leading to abnormal cardiomyocyte LD accumulation and structural and functional deficiencies in their mitochondria. THSWD treatment reduced LD accumulation, restored LD-autophagosome colocalization, and increased mitochondrial structural integrity, membrane potential, and fatty acid β-oxidation. However, these THSWD effects were abolished in the presence of an autophagy inhibitor, implying they occur via a lipophagy-dependent mechanism. Conclusion: Excessive LD accumulation drives mitochondrial dysfunction, contributing to SAP-induced myocardial lipotoxicity. THSWD promotes lipophagy to mitigate lipid accumulation and restore mitochondrial function, and may serve as an effective therapeutic strategy for SAP-induced cardiac metabolic disorders and mitochondrial dysfunction.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信