Zhai Xiaoya, Gao Yefei, Lou Haifei, Meng Liping, Zhou Jiedong, Lin Hui, Xu Fukang
Department of Cardiology, Shaoxing People's Hospital, Shaoxing, People's Republic of China.
Cardiovascular Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315211, People's Republic of China.
Diabetes Metab Syndr Obes. 2025 May 1;18:1373-1388. doi: 10.2147/DMSO.S505138. eCollection 2025.
Hydrogen sulfide (HS), recognized as a significant gasotransmitter, has been shown to effectively reduce damage to cardiomyocytes and endothelial cells caused by diabetes. Its protective effects primarily stem from several mechanisms, including S-sulfhydration of proteins, reduction of cell death, alleviation of mitochondrial damage, improvement of ion channel dysfunction, interaction with nitric oxide, and modulation of angiogenesis. HS is synthesized by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), whose expression is significantly reduced under diabetic conditions, including experimental high-glucose treatment in cells and diabetes mellitus animal models. This review summarizes the protective role of HS and its donors in these pathological processes, highlights existing research gaps-including challenges in the targeted delivery of HS donors, limited clinical translation, and incomplete mechanistic understanding-and discusses future directions for developing targeted HS-based therapeutic strategies.
硫化氢（HS）被认为是一种重要的气体信号分子，已被证明能有效减少糖尿病对心肌细胞和内皮细胞造成的损伤。其保护作用主要源于多种机制，包括蛋白质的S-硫醇化、减少细胞死亡、减轻线粒体损伤、改善离子通道功能障碍、与一氧化氮相互作用以及调节血管生成。HS由胱硫醚β-合酶（CBS）、胱硫醚γ-裂解酶（CSE）和3-巯基丙酮酸硫转移酶（3-MST）合成，在糖尿病条件下，包括细胞实验性高糖处理和糖尿病动物模型中，它们的表达会显著降低。本文综述了HS及其供体在这些病理过程中的保护作用，强调了现有的研究空白，包括HS供体靶向递送的挑战、有限的临床转化以及对机制的不完全理解，并讨论了基于HS的靶向治疗策略的未来发展方向。
