Sullivan Kelli A, Lentz Stephen I, Roberts John L, Feldman Eva L
University of Michigan, Departments of Neurology and Internal Medicine, USA.
Curr Drug Targets. 2008 Jan;9(1):3-13. doi: 10.2174/138945008783431763.
Diabetic neuropathy (DN) is a serious and debilitating complication of both type 1 and type 2 diabetes. Despite intense research efforts into multiple aspects of this complication, including both vascular and neuronal metabolic derangements, the only treatment remains maintenance of euglycemia. Basic research into the mechanisms responsible for DN relies on using the most appropriate animal model. The advent of genetic manipulation has moved mouse models of human disease to the forefront. The ability to insert or delete genes affected in human patients offers unique insight into disease processes; however, mice are still not humans and difficulties remain in interpreting data derived from these animals. A number of studies have investigated and described DN in mice but it is difficult to compare these studies with each other or with human DN due to experimental differences including background strain, type of diabetes, method of induction and duration of diabetes, animal age and gender. This review describes currently used DN animal models. We followed a standardized diabetes induction protocol and designed and implemented a set of phenotyping parameters to classify the development and severity of DN. By applying standard protocols, we hope to facilitate the comparison and characterization of DN across different background strains in the hope of discovering the most human like model in which to test potential therapies.
糖尿病神经病变(DN)是1型和2型糖尿病严重且使人衰弱的并发症。尽管对该并发症的多个方面进行了深入研究,包括血管和神经元代谢紊乱,但唯一的治疗方法仍是维持血糖正常。对DN发病机制的基础研究依赖于使用最合适的动物模型。基因操作技术的出现使人类疾病的小鼠模型走到了前沿。插入或删除人类患者中受影响基因的能力为疾病过程提供了独特的见解;然而,小鼠毕竟不是人类,解释从这些动物获得的数据仍存在困难。许多研究已经对小鼠的DN进行了调查和描述,但由于实验差异,包括背景品系、糖尿病类型、诱导方法和糖尿病持续时间、动物年龄和性别等,很难将这些研究相互比较,也难以与人类DN进行比较。本综述描述了目前使用的DN动物模型。我们遵循标准化的糖尿病诱导方案,设计并实施了一组表型参数来对DN的发展和严重程度进行分类。通过应用标准方案,我们希望促进不同背景品系间DN的比较和特征描述,以期发现最接近人类的模型来测试潜在疗法。