Introduction Diabetic nephropathy (DN) develops in about 40% of patients with type 2 diabetes and remains the leading cause of end-stage renal disease. The mechanisms of DN remain to be elucidated. Oxidative stress is thought to be involved in the development of DN but antioxidant therapy has produced conflicting results. Therefore, we sought to define the role of antioxidant in retarding the development of DN in this study. Research design and methods We generated a new antioxidant/diabetes mouse model, LiasH/HLeprdb/db mice, by crossing db/db mice with LiasH/H mice, which have overexpressed Lias gene (~160%) compared with wild type, and also correspondingly increased endogenous antioxidant capacity. The new model was used to investigate whether predisposed increased endogenous antioxidant capacity was able to retard the development of DN. We systemically and dynamically examined main pathological alterations of DN and antioxidant biomarkers in blood and kidney mitochondria. Results LiasH/HLeprdb/db mice alleviated major pathological alterations in the early stage of DN, accompanied with significantly enhanced antioxidant defense. The model targets the main pathogenic factors by exerting multiple effects such as hypoglycemic, anti-inflammation, and antioxidant, especially protection of mitochondria. Conclusion The antioxidant animal model is not only very useful for elucidating the underlying mechanisms of DN but also brings insight into a new therapeutic strategy for clinical applications. Data are available in a public, open access repository. Data are available on reasonable request.

中文翻译：

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硫辛酸合酶基因过表达减轻Lepr ^db/db小鼠糖尿病肾病

介绍 糖尿病肾病 (DN) 发生在约 40% 的 2 型糖尿病患者中，并且仍然是终末期肾病的主要原因。DN 的机制仍有待阐明。氧化应激被认为与 DN 的发展有关，但抗氧化疗法产生了相互矛盾的结果。因此，我们试图在本研究中确定抗氧化剂在延缓 DN 发展中的作用。研究设计和方法 我们通过将 db/db 小鼠与 LiasH/H 小鼠杂交，生成了一种新的抗氧化剂/糖尿病小鼠模型 LiasH/HLeprdb/db 小鼠，与野生型相比，Lias 基因过表达（~160%），并且相应地增加了内源性抗氧化能力。新模型用于研究内源性抗氧化能力的增加是否能够延缓 DN 的发展。我们系统和动态地检查了血液和肾脏线粒体中 DN 和抗氧化生物标志物的主要病理改变。结果 LiasH/HLeprdb/db 小鼠减轻了 DN 早期的主要病理改变，同时显着增强了抗氧化防御。该模型通过发挥降血糖、抗炎和抗氧化等多重作用，尤其是对线粒体的保护作用，针对主要致病因素。结论抗氧化动物模型不仅对阐明DN的潜在机制非常有用，而且为临床应用提供了一种新的治疗策略。数据在公共、开放存取的存储库中可用。可应合理要求提供数据。