Yin Chang, Liu Yanhua, Cheng Shuohan, Yang Shu, Lan Tianfang, Jin Hongtao, Zhou Zhi, Wang Zhonghua, Abliz Zeper
Key Laboratory of Mass Spectrometry Imaging and Metabolomics (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China.
Center for Imaging and Systems Biology, College of Life and Environmental Sciences, Minzu University of China, 27 Zhongguancun South Avenue, Beijing, 100081, China.
Anal Bioanal Chem. 2025 Jun 23. doi: 10.1007/s00216-025-05969-y.
Diabetic cardiomyopathy (DCM), a cardiac complication of diabetes, is characterized by diastolic dysfunction, myocardial fibrosis, and structural remodeling. Carbonyl-containing metabolites (CCMs) play a critical role in driving DCM pathogenesis through metabolic dysfunction, oxidative stress, and lipid peroxidation. In this study, we employed an on-tissue chemical derivatization (OTCD)-based air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) approach to investigate spatial metabolic alterations of CCMs in the diabetic rat heart. This method enabled the spatial profiling of 369 CCMs-including 137 fatty aldehydes (FALs), 214 oxo fatty acids (OFAs), and 18 sterol-type lipids (STs)-across cardiac tissue sections. This expanded metabolite coverage revealed marked spatial heterogeneity in cardiac metabolism. Comparative analysis between diabetic and control rats identified 162 significantly altered CCMs, highlighting localized metabolic dysregulation associated with DCM. To explore potential therapeutic interventions, we further evaluated the metabolic impact of ferulic acid, a candidate agent for myocardial protection. High-dose ferulic acid treatment significantly modulated 43 differential CCMs, attenuated pyruvate accumulation, restored fatty aldehyde levels, and improved the profile of oxidized fatty acids. These findings suggest that ferulic acid ameliorates metabolic dysfunction by exerting antioxidant and anti-inflammatory effects, while enhancing mitochondrial function and lipid metabolism. Overall, this study demonstrates the utility of OTCD-AFADESI-MSI for spatially resolved metabolomic analysis of carbonyl stress in DCM and supports the therapeutic potential of ferulic acid in managing diabetic heart injury.
糖尿病性心肌病（DCM）是糖尿病的一种心脏并发症，其特征为舒张功能障碍、心肌纤维化和结构重塑。含羰基代谢物（CCMs）通过代谢功能障碍、氧化应激和脂质过氧化在驱动DCM发病机制中起关键作用。在本研究中，我们采用基于组织化学衍生化（OTCD）的气流辅助解吸电喷雾电离质谱成像（AFADESI-MSI）方法来研究糖尿病大鼠心脏中CCMs的空间代谢变化。该方法能够对心脏组织切片中的369种CCMs进行空间分析，包括137种脂肪醛（FALs）、214种氧代脂肪酸（OFAs）和18种甾醇类脂质（STs）。这种扩大的代谢物覆盖范围揭示了心脏代谢中显著的空间异质性。糖尿病大鼠与对照大鼠之间的比较分析确定了162种显著改变的CCMs，突出了与DCM相关的局部代谢失调。为了探索潜在的治疗干预措施，我们进一步评估了阿魏酸（一种心肌保护候选药物）的代谢影响。高剂量阿魏酸治疗显著调节了43种差异CCMs，减少了丙酮酸积累，恢复了脂肪醛水平，并改善了氧化脂肪酸的分布。这些发现表明，阿魏酸通过发挥抗氧化和抗炎作用，同时增强线粒体功能和脂质代谢来改善代谢功能障碍。总体而言，本研究证明了OTCD-AFADESI-MSI在DCM中羰基应激的空间分辨代谢组学分析中的实用性，并支持了阿魏酸在管理糖尿病性心脏损伤方面的治疗潜力。
