糖尿病周围神经病变的治疗：从动物模型中学到了什么？
Treatment for Diabetic Peripheral Neuropathy: What have we Learned from Animal Models?
机构信息
Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242 USA.
Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA, 52246 USA.
出版信息
Curr Diabetes Rev. 2022;18(5):e040521193121. doi: 10.2174/1573399817666210504101609.
INTRODUCTION
Animal models have been widely used to investigate the etiology and potential treatments for diabetic peripheral neuropathy. What we have learned from these studies and the extent to which this information has been adapted for the human condition will be the subject of this review article.
METHODS
A comprehensive search of the PubMed database was performed, and relevant articles on the topic were included in this review.
RESULTS
Extensive study of diabetic animal models has shown that the etiology of diabetic peripheral neuropathy is complex, with multiple mechanisms affecting neurons, Schwann cells, and the microvasculature, which contribute to the phenotypic nature of this most common complication of diabetes. Moreover, animal studies have demonstrated that the mechanisms related to peripheral neuropathy occurring in type 1 and type 2 diabetes are likely different, with hyperglycemia being the primary factor for neuropathology in type 1 diabetes, which contributes to a lesser extent in type 2 diabetes, whereas insulin resistance, hyperlipidemia, and other factors may have a greater role. Two of the earliest mechanisms described from animal studies as a cause for diabetic peripheral neuropathy were the activation of the aldose reductase pathway and increased non-enzymatic glycation. However, continuing research has identified numerous other potential factors that may contribute to diabetic peripheral neuropathy, including oxidative and inflammatory stress, dysregulation of protein kinase C and hexosamine pathways, and decreased neurotrophic support. In addition, recent studies have demonstrated that peripheral neuropathy-like symptoms are present in animal models, representing pre-diabetes in the absence of hyperglycemia.
CONCLUSION
This complexity complicates the successful treatment of diabetic peripheral neuropathy, and results in the poor outcome of translating successful treatments from animal studies to human clinical trials.
简介
动物模型已被广泛用于研究糖尿病周围神经病变的病因和潜在治疗方法。本综述将讨论我们从这些研究中学到的知识，以及这些信息在多大程度上适用于人类疾病。
方法
对 PubMed 数据库进行了全面检索，并纳入了与该主题相关的综述文章。
结果
对糖尿病动物模型的广泛研究表明，糖尿病周围神经病变的病因复杂，多种机制影响神经元、雪旺细胞和微血管，导致这种最常见的糖尿病并发症的表型特征。此外，动物研究表明，1 型和 2 型糖尿病相关的周围神经病变机制可能不同，高血糖是 1 型糖尿病神经病变的主要因素，在 2 型糖尿病中作用较小，而胰岛素抵抗、血脂异常和其他因素可能起更大作用。动物研究最早描述的两种导致糖尿病周围神经病变的机制是醛糖还原酶途径的激活和非酶糖基化的增加。然而，持续的研究已经确定了许多其他可能导致糖尿病周围神经病变的潜在因素，包括氧化和炎症应激、蛋白激酶 C 和己糖胺途径的失调以及神经营养支持的减少。此外，最近的研究表明，在没有高血糖的情况下，动物模型中存在类似于周围神经病变的症状，代表了糖尿病前期。
结论
这种复杂性使糖尿病周围神经病变的治疗变得复杂，并且导致从动物研究到人类临床试验成功治疗的结果不佳。
Zotero 插件