Takeda Yuji, Shimomura Tomoko, Wakabayashi Ichiro
Department of Environmental and Preventive Medicine, Hyogo College of Medicine.
Nihon Eiseigaku Zasshi. 2014;69(3):166-76. doi: 10.1265/jjh.69.166.
A comprehensive understanding of the pathogenic mechanism is the prerequisite for proper disease management. However, the mechanisms of diabetes mellitus and diabetic complication remain extremely complicated and unresolved. While immune reactions are involved in the pathogenesis of diabetes and diabetic complication, the diabetic condition itself can influence immune responses. Furthermore, both diabetes and immune reactions are regulated by genetic and environmental factors. As a result, animal models have evolved to be powerful research tools to elucidate the complicated mechanisms for the pathogenesis of diabetes. Recently, various animal models of diabetes have been developed in rats, which provide advantages over mouse models in the scale of tissue samples and variation in type 2 diabetes models. In this review, we introduced rat models of diabetes and summarized the immune reactions in diabetic rats to propose the relationship between immune reactions and diabetes. Type 1 diabetes is induced by self-reactive cellular immune reactions. On the other hand, type 2 diabetes in rat models is associated with augmentation of innate immune reactions and increased humoral immunity. For example, helper T (Th) 1/Th17 cells are prevalent in non-obese type 1 diabetes rats (diabetes-prone BioBreeding rats), while non-obese type 2 diabetes rats (Goto-Kakizaki rat) show higher levels of natural IgM and T cell ratios with elevated Th2 cells compared with Wister rats. The investigation of immunological disorders in various diabetic rat models is useful to elucidate complicated mechanisms for the pathophysiology of diabetes. In future studies, immunological experimentations altering Th1/Th17 or Th2 cell levels and natural immune reactions may lend support to understanding the causes of diabetes and predicting the pathological conditions in diabetes.
全面了解致病机制是妥善管理疾病的前提。然而,糖尿病及其并发症的机制仍然极其复杂且尚未解决。虽然免疫反应参与了糖尿病及其并发症的发病过程,但糖尿病本身也会影响免疫反应。此外,糖尿病和免疫反应均受遗传和环境因素的调控。因此,动物模型已发展成为阐明糖尿病发病复杂机制的有力研究工具。最近,在大鼠中建立了各种糖尿病动物模型,这些模型在组织样本规模和2型糖尿病模型的多样性方面比小鼠模型更具优势。在本综述中,我们介绍了糖尿病大鼠模型,并总结了糖尿病大鼠的免疫反应,以探讨免疫反应与糖尿病之间的关系。1型糖尿病由自身反应性细胞免疫反应诱发。另一方面,大鼠模型中的2型糖尿病与固有免疫反应增强和体液免疫增加有关。例如,辅助性T(Th)1/Th17细胞在非肥胖1型糖尿病大鼠(糖尿病倾向的BioBreeding大鼠)中占优势,而非肥胖2型糖尿病大鼠(Goto-Kakizaki大鼠)与Wister大鼠相比,天然IgM水平和T细胞比例更高,Th2细胞水平升高。对各种糖尿病大鼠模型免疫紊乱的研究有助于阐明糖尿病病理生理学的复杂机制。在未来的研究中,改变Th1/Th17或Th2细胞水平以及天然免疫反应的免疫学实验可能有助于理解糖尿病的病因并预测糖尿病的病理状况。