自发与诱发2型糖尿病小鼠模型的比较研究

Comparison of spontaneous type 2 diabetes mice with induced diabetes mice

目的为比较自发与诱发2型糖尿病小鼠模型在糖代谢,胰岛素抵抗以及炎症反应等方面的差异。方法动物分为正常对照组,诱发模型组和自发模型组,每组10只。正常对照组:正常11周龄C57BL/6J小鼠;诱发模型组:用高脂饲料结合STZ诱导11周龄C57BL/6J小鼠建立糖尿病模型;自发模型组:选择8周龄的C57BL/Ks J-db/db鼠;监测各组动物八周内体重,空腹血糖,糖耐量变化;检测实验前后FINS,AUC,HOMA-IR以及TNF-α,IL-18,IL-1β,INF-γ含量的变化;八周后处死动物取肝、肾、胰腺、睾丸、骨骼肌等组织做病理分析。结果在实验周期内,自发模型组体重持续上升,而诱发模型组体重明显下降;诱发模型组小鼠血糖八周后有所下降,而自发模型组小鼠稳定维持高血糖;诱发模型组的FINS上升,AUC以及HOMA-IR明显下降,自发模型组FINS无显著变化,AUC以及HOMA-IR均显著上升;模型建立初,两种模型鼠血清中促炎症因子(TNF-α,IL-18,IL-1β,INF-γ)的含量均比正常对照组要高。在第八周时,诱发模型组鼠促炎症因子部分含量有所下降,自发模型组促炎症因子的含量都明显的升高;两种模型鼠的胰腺等组织均出现明显的炎性病变。结论八周后自发性2型糖尿病模型糖代谢异常以及炎症反应都日渐加重,长时间维持高血糖症状;诱发性2型糖尿病模型在饲养八周后糖代谢以及炎症反应部分缓解,高血糖症状部分好转。

Objective To investigate biological parameters and morphology in spontaneous type 2 diabetes C57BL/ Ks J-db / db mice and mice with type 2 diabetes mellitus which induced by high-fat diet and streptozotocin injections.Methods C57 BL /6J mice were divided randomly into normal control group,Induced Group,and Spontaneous Group with10 mice in each group; Induced Group ： The 11 weeks old C57 BL /6J mice were fed on a high-fat diet before intraperitoneal injections of STZ; Spontaneous Group： 8 weeks old C57 BL / Ks J- db / db mice（ db / db）; The body weight,Fasting blood glucose（ FBG）,oral glucose tolerance test（ OGTT） was detected every week for 28 days. FINS,AUC,IR index and proinflammation factors（ TNF-α,IL-18,IL-1β,INF-γ） were evaluated in the beginning and 8thweek. At the end of experiment,the mice were sacrificed for organ and morphological study. Results The weight of Spontaneous Group were higher than Induced Group, both of them are higher than normal group significantly; Non-fasting blood glucoseconcentrations of Spontaneous Group mice were higher over Induced Group; In 8thweek the abnormal glucose levels of Spontaneous Group extraordinary stability, however, in Induced Group drops obviously; the FINS was increased in Spontaneous Group,but have no significantly change in Induced Group,both AUC and HOMA-IR index Show a significant downtrend in Induced Group,However,in Spontaneous Group,the rising trend of AUC and HOMA-IR are stabe; The content of the pro-inflammatory factor（ TNF-α,IL-18,IL-1β,INF-γ） in both diabetes animal are more than normal group. In 8th week the content of pro-inflammatory factor was decreased in Induced Group,but increased in Spontaneous Group significantly; Pathologic results showed that pancreas, kidney, liver, muscle, and testis, appeared serious inflammatory pathological deterioration in two kinds of diabetes models mice. Conclusions During 8weeks the Spontaneous diabetes animal showed abnormal glucose metabolism,and high concentration of pro-inflammatory cytokines which Symptoms of type 2 diabetes become more and more serious.; glucose metabolism and inflammation showed improved in induced animal model.