Abstract

Reactive oxygen species (ROS) has been implicated as a contributor to both the onset and the progression of diabetes, however how does redox state affect diabetes has not been fully understood. Here we study the role of redox interference on pancreatic mitochondria and the progression of diabetes. We applied streptozotocin (STZ) to establish diabetes mellitus (DM) model in rats, applied FeSO₄ to produce oxidative stress (OS) and Ganoderma lucidum polysaccharides as antioxidant intervention (AO). Our results showed that in OS and DM group, oxidative stress caused the imbalance of redox state, resulting in higher lipid peroxidation level and lower antioxidant level, while AO treatment group reduced blood glucose by repairing the redox balance. The insulin level has the order of Normal Control (NC)<AO < DM < OS, suggesting oxidative stress promoted insulin secretion in a compensatory mechanism. The Mn-SOD expression in OS groups of pancreas were significantly lower than other groups, while the p53 expression was significantly higher. The mitochondrial ultrastructure of pancreatic β cells were impaired in DM group, and the damage was more severe in OS group, paralleled with significantly reduced secretory granules, both of which were repaired in the AO group. Our results demonstrated that the redox state can affect the blood glucose of diabetic rats, and oxidative stress can aggravate diabetes, while the early antioxidant treatment can alleviate the process of diabetes through reversing the imbalance of redox state and repairing the pancreatic mitochondria. These results suggest that redox balance plays an important role in the treatment of diabetes.

摘要

活性氧（ROS）被认为是糖尿病发作和发展的原因，但是氧化还原状态如何影响糖尿病尚未得到充分了解。在这里，我们研究氧化还原干扰对胰腺线粒体和糖尿病进展的作用。我们应用链脲佐菌素（STZ）建立大鼠糖尿病（DM）模型，应用FeSO ₄产生氧化应激（OS）和灵芝多糖作为抗氧化剂干预（AO）。我们的结果表明，在OS和DM组中，氧化应激导致氧化还原状态失衡，从而导致较高的脂质过氧化水平和较低的抗氧化剂水平，而AO治疗组则通过修复氧化还原平衡来降低血糖。胰岛素水平的顺序为正常对照（NC）<AO <DM <​​OS，表明氧化应激以补偿机制促进了胰岛素的分泌。胰腺OS组中Mn-SOD表达明显低于其他组，而p53表达则明显高于其他组。DM组胰腺β细胞的线粒体超微结构受损，而OS组损伤更严重，同时分泌颗粒明显减少，两者均在AO组中修复。我们的结果表明，氧化还原状态可以影响糖尿病大鼠的血糖，氧化应激可以加剧糖尿病，而早期的抗氧化剂治疗可以通过逆转氧化还原状态的失衡和修复胰腺线粒体来缓解糖尿病。这些结果表明氧化还原平衡在糖尿病的治疗中起重要作用。