诱发性2型糖尿病小鼠模型与自发性db／db 小鼠特性的比较

摘要

Object To establish an induced mouse model of type 2 diabetes mellitus, and compare it with db/db mouse model of spontaneous type 2 diabetes.To evaluate the two mouse models objectively, and provide an experimental basis for the choice of animal model and its practical application in diabetes studies.Methods A mouse model of induced type 2 diabetes was established by feeding C57BL/6J mice with high-fat and high-sugar diet for four weeks and taking daily intraperitoneal injections of streptozotocin ( STZ) for consecutive 3 days.Four weeks after infection, the gross appearance of kidney and liver of the mice was assessed, glucose tolerance was tested, serum biochemical indices and expression of se-rum IL-2, IL-4, IL-6, IFN-γ, TNF-α, IL-17, and IL-10 were assayed, and were compared with those of the db/db mouse models of spontaneous type 2 diabetes.Results Obvious differences were found in the kidneys and liver gross appearance of the two types of mouse models and the control group.Both the two groups showed significant differences in the blood glu-cose levels at each time point (P<0.05) and low glucose tolerance function, but there were no significant differences in blood glucose levels of the two types of mouse models.Compared with the control group, the serum biochemical indices GLU, GHOL and LDLC of the two types of mouse models were significantly increased (P<0.05).Meanwhile, the blood lipid level of the mouse model of induced type 2 diabetes was higher than that of the db/db mouse models of spontaneous type 2 diabetes.In comparison of immune indices, except IL-2,the serum cytokine levels of the two types of mouse models were significantly higher than those of the control group (P<0.05).Moreover, the serum cytokine levels of db/db mice were higher than those in the mouse models of induced type 2 diabetes, and the IL-6, IFN-γ, TNF-αalso had obvious differences.Conclusions Both the two types of mouse models of type 2 diabetes successfully simulate the human diabetes to some extent, but there are still certain differences according to different etiology of diabetes.We would suggest that peo-ple may take our data as reference and chose appropriate mouse models according to the requirement of their research.%目的：建立诱发性2型糖尿病小鼠模型，并将其与自发性2型糖尿病小鼠db／db进行比较分析。客观评价两种2型糖尿病小鼠模型，为糖尿病研究中动物模型的选择与实际应用提供实验依据。方法高脂饲料喂养C57BL／6J小鼠4周，腹腔连续3次注射STZ，建立诱发性2型糖尿病小鼠模型。感染后4周，大体肉眼观察小鼠的肝脏、肾脏，测定糖耐量，血清生化指标及血清细胞因子IL－2、IL－4、IL－6、IFN－γ、TNF－α、IL－17、IL－10表达量，将其与同龄的自发性2型糖尿病小鼠db／db进行比较分析。结果肉眼观察发现，两组模型小鼠的肝脏、肾脏与对照组均具有明显差异。糖耐量分析中，两组模型小鼠与对照组小鼠各时间点的血糖值均具有统计学差异（ P＜0．05），耐糖功能低下，两组模型小鼠间血糖值无统计学差异。血液生化指标中，与对照组小鼠相比，两组模型小鼠GLU、CHOL、LDLC明显升高（P＜0．05）；两组模型小鼠相互比较，诱发性2型糖尿病小鼠血脂水平较高（P＜0．05）。免疫指标比较显示：除IL－2外，两组模型小鼠血清中细胞因子水平均较对照组小鼠明显升高（ P＜0．05），而db／db 小鼠血清中细胞因子表达较诱发性糖尿病小鼠高，其中IL－6、IFN－γ、TNF－α具有显著性差异（ P＜0．05）。结论两组2型糖尿病模型小鼠均在一定程度上模拟了人类糖尿病患者症状，但由于糖尿病产生的原因不同而存在着一定的差异，研究者可根据实际需要参照相关数据进行选择。