Allen Terri J, Cooper Mark E, Lan Hui Y
Department of Medicine, Baylor College of Medicine, One Baylor Plaza, N520, Houston, TX 77030, USA.
Curr Atheroscler Rep. 2004 May;6(3):197-202. doi: 10.1007/s11883-004-0032-7.
The study of experimental diabetic nephropathy in rodent models has led to many changes in the clinical management of human diabetic nephropathy. With the development of technology to generate knockout and transgenic animals, the mouse has become a favored species in medical research. There are several genetic mouse models of diabetes, with the majority being models of type 2 diabetes mellitus. These include the hypoinsulinemic non-obese diabetic mouse, the Kkay mouse, the New Zealand obese mouse, the hyperinsulinemic ob/ob mouse, and the different strains of obese hyperinsulinemic db/db mouse. Each of these models displays some renal changes, but by far the best model of renal disease and the one that is the most studied is the db/db mouse. The db/db mouse displays substantial glomerular pathology, including mesangial matrix expansion and modest albuminuria. It has been reported that the db/db mouse has a decline in creatinine clearance after 5 months of age, but more specific approaches are warranted to confirm these findings. A number of intervention studies show renoprotection in this model. Although mice have many advantages, such as being able to be cross-bred with genetically manipulated animals, in many ways they are not very similar to humans, and in some respects the rat may be a better choice, particularly in relation to some features of end-organ injury.
啮齿动物模型中实验性糖尿病肾病的研究已给人类糖尿病肾病的临床管理带来诸多改变。随着基因敲除和转基因动物技术的发展，小鼠已成为医学研究中备受青睐的物种。有多种糖尿病基因小鼠模型，其中大多数是2型糖尿病模型。这些模型包括低胰岛素血症非肥胖糖尿病小鼠、Kkay小鼠、新西兰肥胖小鼠、高胰岛素血症ob/ob小鼠以及不同品系的肥胖高胰岛素血症db/db小鼠。这些模型均呈现出一些肾脏变化，但迄今为止，肾脏疾病的最佳模型且研究最多的是db/db小鼠。db/db小鼠表现出明显的肾小球病变，包括系膜基质扩张和轻度蛋白尿。据报道，db/db小鼠在5月龄后肌酐清除率下降，但需要更具体的方法来证实这些发现。多项干预研究表明该模型存在肾脏保护作用。尽管小鼠有许多优点，比如能够与基因操作动物进行杂交繁育，但在很多方面它们与人类不太相似，在某些方面大鼠可能是更好的选择，特别是在终末器官损伤的某些特征方面。
