氧化应激：糖尿病并发症的促发因素及潜在治疗靶点

Metabolic Diseases Diabetes Oxidative Stress Mitochondrial Dysfunction

糖尿病 (DM) 是全球公共卫生面临的主要挑战之一，会显著增加死亡风险。氧化应激是高血糖诱导的糖尿病血管损伤发生的关键驱动因素，包括微血管和心血管并发症。内皮细胞线粒体超氧阴离子的过度生成是糖尿病相关代谢异常的直接后果，并进一步激活五条主要致病通路：(1) 多元醇途径通量增加；(2) 晚期糖基化终产物 (AGEs) 生成增加；(3) AGE 受体表达增强；(4) 蛋白激酶 C (PKC) 各亚型的激活；(5) 己糖胺途径过度活跃 ^{[1] [2]}。

除代谢紊乱外，氧化应激还强烈驱动炎症信号。活性氧 (ROS) 可促进 NF-κB、NLRP3 炎性小体、iNOS 和 COX-2 的激活，导致持续的细胞因子产生及内皮功能障碍。持续的氧化应激还会引发“代谢记忆”现象，即使血糖得到控制，血管损伤仍会继续。受损的线粒体生物发生、降低的 NAD⁺/SIRT 信号以及线粒体 DNA 损伤会进一步加剧这一慢性炎症状态 ^{[1] [3]}。

使用维生素 E 或其他抗氧化剂的抗氧化治疗被认为是一种针对血管氧化应激的对症治疗手段。α-硫辛酸作为具有自我再生能力的线粒体抗氧化剂，可在体内恢复内皮功能。Ruboxistaurin 是一种蛋白激酶 Cβ 亚型抑制剂，已被证明可降低视网膜氧化应激。PJ34 通过阻断多聚 (ADP-核糖) 聚合酶来调控受到氧化压力的细胞的线粒体功能。这两种化合物也能改善高糖诱导的内皮功能障碍。此外，噻唑烷二酮类、他汀类、ACE 抑制剂及 ATI 抑制剂均具有较强的抗氧化活性，可能对糖尿病并发症具有潜在益处 ^[4]。

总之，大量证据表明氧化应激在糖尿病并发症中发挥核心作用。针对氧化还原失衡、线粒体功能障碍以及 ROS 介导的炎症信号的抗氧化治疗策略具有显著的治疗潜力，并持续成为糖尿病研究的重要方向。

Articles
Products
Targets/Pathways

Cat.No.	Product Name	Disease Area	Target	Category
HY-10195	Ruboxistaurin	Neurodegenerative Disease; Digestive System Inflammation; Glucose Metabolism; Cancer; Digestive System Disease	PKC	Inhibitors & Agonists
HY-10930	UNC0321	Leukemia/Lymphoma/Myeloma; Leukemia/Lymphoma/Myeloma; Digestive System Inflammation; Glucose Metabolism; Digestive System Disease	Histone Methyltransferase; GCGR; Apoptosis	Inhibitors & Agonists
HY-13688A	PJ34	Breast Cancer; Pancreatic Cancer; Ovarian Cancer; Digestive System Cancer; Urogenital Cancer; Neurological, Eye or Ear Disease	PARP	Inhibitors & Agonists
HY-13982	JSH-23	Leukemia/Lymphoma/Myeloma; Obesity; Breast Cancer; Prostate Cancer; Liver Cancer; Leukemia/Lymphoma/Myeloma; Pancreatic Cancer; Ovarian Cancer; Depression; Pain; Digestive System Inflammation; Glucose Metabolism; Digestive System Cancer; Urogenital Cancer	NF-κB	Inhibitors & Agonists
HY-145846	iNOs-IN-1	Lung Fibrosis; Rheumatoid Arthritis; Prostate Cancer; Depression; Pain; Autoimmune Disease; Digestive System Inflammation; Urogenital Cancer; Digestive System Disease	NO Synthase; Interleukin Related	Inhibitors & Agonists
HY-14771	Imeglimin	Digestive System Inflammation; Glucose Metabolism; Digestive System Disease	Mitochondrial Metabolism; Reactive Oxygen Species (ROS)	Inhibitors & Agonists
HY-14771A	Imeglimin hydrochloride	SARS-CoV-2 Infection; Digestive System Inflammation; Glucose Metabolism; Digestive System Disease	Mitochondrial Metabolism; Reactive Oxygen Species (ROS)	Inhibitors & Agonists
HY-14892	Gemigliptin	Cancer; Metabolic or Endocrine Disease	Dipeptidyl Peptidase	Inhibitors & Agonists
HY-150630	ALR2-IN-1	Glucose Metabolism	Aldose Reductase	Inhibitors & Agonists
HY-16433	Risarestat	Glucose Metabolism; Inflammation or Immune System Disease	Aldose Reductase	Inhibitors & Agonists
HY-17374	Benfotiamine	SARS-CoV-2 Infection; Viral Infection; Glucose Metabolism; Inflammation or Immune System Disease	HIV; SARS-CoV	Inhibitors & Agonists
HY-17408	Mevastatin	Bacterial Infection; Digestive System Inflammation; Cardiovascular Disease; Cancer; Neurological, Eye or Ear Disease; Metabolic or Endocrine Disease; Digestive System Disease	HMG-CoA Reductase (HMGCR); Bacterial; Autophagy; Apoptosis; Antibiotic	Inhibitors & Agonists
HY-175331	ALR2-IN-7	Glucose Metabolism; Cancer	Aldose Reductase	Inhibitors & Agonists
HY-18731	1400W Dihydrochloride	Parkinson's Disease; Lung Fibrosis; Digestive System Inflammation; Cardiovascular Disease; Cancer; Digestive System Disease	NO Synthase; Apoptosis	Inhibitors & Agonists
HY-18733	Lipoic acid	Viral Infection; Digestive System Inflammation; Cancer; Digestive System Disease	Mitochondrial Metabolism; Endogenous Metabolite; Reactive Oxygen Species (ROS)	Inhibitors & Agonists
HY-19696B	Tauroursodeoxycholate dihydrate	Parkinson's Disease; Leukemia/Lymphoma/Myeloma; Obesity; Lung Fibrosis; Breast Cancer; Prostate Cancer; Liver Cancer; Leukemia/Lymphoma/Myeloma; Pancreatic Cancer; Ovarian Cancer; Viral Infection; Depression; Pain; Digestive System Inflammation; Glucose Metabolism; Digestive System Cancer; Urogenital Cancer	Caspase; Apoptosis; Endogenous Metabolite; IRE1; NF-κB; JNK; Reactive Oxygen Species (ROS); Akt	Inhibitors & Agonists
HY-B0227	Ketoprofen	SARS-CoV-2 Infection; Rheumatoid Arthritis; Colorectal Cancer; Prostate Cancer; Pancreatic Cancer; Depression; Autoimmune Disease; Digestive System Cancer; Urogenital Cancer; Metabolic or Endocrine Disease	COX	Inhibitors & Agonists
HY-B1202	Alrestatin	Glucose Metabolism	Aldose Reductase	Inhibitors & Agonists
HY-B2163	Astaxanthin	Blood or Cardiovascular Disease; Metabolic or Endocrine Disease	PPAR; Reactive Oxygen Species (ROS); STAT; NF-κB; Apoptosis	Inhibitors & Agonists
HY-N0279	Cardamonin	Hypertension; Leukemia/Lymphoma/Myeloma; Obesity; Lung Fibrosis; Rheumatoid Arthritis; Lung Cancer; Breast Cancer; Colorectal Cancer; Prostate Cancer; Gastric Cancer; Liver Cancer; Leukemia/Lymphoma/Myeloma; Pancreatic Cancer; Ovarian Cancer; Depression; Pain; Autoimmune Disease; Digestive System Inflammation; Glucose Metabolism; Digestive System Cancer; Urogenital Cancer	NF-κB; STAT; Wnt; β-catenin; Bcl-2 Family; Apoptosis	Inhibitors & Agonists
HY-N0411	β-Carotene	Metabolic or Endocrine Disease	Endogenous Metabolite; Apoptosis; Reactive Oxygen Species (ROS)	Inhibitors & Agonists
HY-N0441	Neferine	Leukemia/Lymphoma/Myeloma; Obesity; Breast Cancer; Prostate Cancer; Liver Cancer; Leukemia/Lymphoma/Myeloma; Pancreatic Cancer; Ovarian Cancer; Depression; Pain; Digestive System Inflammation; Glucose Metabolism; Digestive System Cancer; Urogenital Cancer	NF-κB; Autophagy; Apoptosis	Inhibitors & Agonists
HY-N0457	Chicoric acid	Digestive System Inflammation; Glucose Metabolism; Digestive System Disease	Reactive Oxygen Species (ROS); Apoptosis	Inhibitors & Agonists
HY-N0523	Gallic acid	SARS-CoV-2 Infection; Rheumatoid Arthritis; Colorectal Cancer; Prostate Cancer; Pancreatic Cancer; Depression; Autoimmune Disease; Digestive System Inflammation; Glucose Metabolism; Digestive System Cancer; Urogenital Cancer	COX; Reactive Oxygen Species (ROS); Apoptosis; Ferroptosis; Endogenous Metabolite	Inhibitors & Agonists
HY-N0621	Morin	Parkinson's Disease; Leukemia/Lymphoma/Myeloma; Obesity; Colorectal Cancer; Leukemia/Lymphoma/Myeloma; Digestive System Inflammation; Cardiovascular Disease; Glucose Metabolism; Digestive System Cancer	Phosphatase; Apoptosis; Reactive Oxygen Species (ROS); Insulin Receptor	Inhibitors & Agonists
HY-N0683	α-Vitamin E	Viral Infection; Bacterial Infection; Glucose Metabolism; Cancer; Neurological, Eye or Ear Disease; Inflammation or Immune System Disease	Bacterial; Influenza Virus; Reactive Oxygen Species (ROS); Ferroptosis; Endogenous Metabolite	Inhibitors & Agonists
HY-W015913	Sodium 2-oxopropanoate	Inflammation or Immune System Disease; Metabolic or Endocrine Disease	Reactive Oxygen Species (ROS); Endogenous Metabolite	Inhibitors & Agonists
HY-L040	Anti-diabetic Compound Library	/	/	Screening Libraries

Reference

[1]. An, Y., et al., (2023). The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction. Cardiovascular diabetology, 22(1), 237. [Content Brief]

[2]. Giacco, F., & Brownlee, M. (2010). Oxidative stress and diabetic complications. Circulation research, 107(9), 1058–1070. [Content Brief]

[3]. Roy B. (2025). Pathophysiological Mechanisms of Diabetes-Induced Macrovascular and Microvascular Complications: The Role of Oxidative Stress. Medical sciences (Basel, Switzerland), 13(3), 87. [Content Brief]

[4]. Ceriello A. (2003). New insights on oxidative stress and diabetic complications may lead to a "causal" antioxidant therapy. Diabetes care, 26(5), 1589–1596. [Content Brief]

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