不同剂量STZ诱导小鼠糖尿病模型的发病机制

Pathogenesis of mouse diabetes mellitus models induced by different doses of streptozotocin

目的:探讨不同剂量链脲佐菌素(STZ)多次注射诱导小鼠糖尿病模型的发生机制以及糖尿病的发生与自身免疫应答的关系。方法:昆明小鼠40只随机分为正常对照组(Ⅰ组)及20、40、80 mg.kg-1STZ组(Ⅱ、Ⅲ、Ⅳ组)。腹腔注射不同剂量STZ诱导小鼠糖尿病作为动物模型。葡萄糖(Glu)测定试剂盒与尿液分析试纸条联合检测小鼠血糖和尿糖的变化,光镜观察胰岛的组织学改变情况,ELISA间接法检测小鼠血清中胰岛素抗体(IAA)的水平,淋巴细胞转化试验(MTT法)检测小鼠胸腺和脾脏的T淋巴细胞功能。结果:对照组血糖基本无变化,模型组血糖值随时间增加而增加;注射STZ后第4周,尿糖结果Ⅰ组均为(-);Ⅱ组中5只(-),其余均>+;Ⅲ组中2只(-),其余均>;Ⅳ组均>。不同剂量STZ诱导小鼠胰岛β细胞损伤的病理改变和程度均有所差异。Ⅱ组和Ⅲ组的IAA高于对照组(P<0.05),而Ⅳ组与对照组比较差异无显著性(P>0.05)。与对照组比较,Ⅱ组和Ⅲ组的脾细胞(成熟的T淋巴细胞)对ConA的刺激表现为功能增强,而胸腺细胞(不成熟的T淋巴细胞)对ConA的刺激则表现为功能降低;但Ⅳ组与对照组比较差异无显著性(P>0.05)。结论:3种剂量STZ均可诱导不同程度的糖尿病发生。大剂量STZ(80 mg.kg-1)可诱导小鼠产生2型糖尿病;而小剂量STZ(20和40 mg.kg-1)则诱导产生1型糖尿病,以40 mg.kg-1STZ诱导的1型糖尿病的效果为最佳。

Objective To explore the pathogenesis of type 1 diabetes mellitus （T1DM） induced by different doses of streptozotocin （STZ） and its relations with autoimmune response. Methods Forly KM mice were divided into control group （group Ⅰ ） and 20, 40, 80 mg·kg^-1 STZ treated groups （group Ⅱ , Ⅲ, Ⅳ）. Animal models of diabetes mellitus were induced by different doses of STZ through intra peritoneal injection. Blood and urine glucose （Glu） levels were detected with glucose detecting kit and urine analyzing papers respectively. Pancreatic histological changes of islets were observed under light microscope. The level of insulin autoantibodies （IAA） in serum was detected by indirect ELISA. The functions of T lymphocytes in mouse spleen and thymus were detected by Lymphocytes Proliferation Assay （MTT method）. Results The blood glucose in group Ⅰchanged nothing. The blood Glu levels in group Ⅱ and Ⅲ increased as times went by. Four weeks after injection of STZ, the urine Glu in group Ⅰ were all negative, in groupⅡ 5 negative and others 〉 ＋, in group Ⅲ 2 negative and others 〉＋＋, in group Ⅳ all〉 卌. The changes and degrees of pancreatic islet β cells injured by difference doses of STZ were different. The IAA levels in group Ⅱ and Ⅲ were higher than that in control group （P〈0.05）, but there was no difference between group Ⅳ and control group. Spleenocytes （mature T lymphocytes） were highly proliferated by ConA and the thymocytes （immature T lymphocytes） were lowly proliferated by ConA in group Ⅱ and Ⅲ. However, there was no difference between group Ⅳand control group. Conclusion Three different doses of STZ （20, 40, 80 mg· kg^-1） can induce different kinds of DM. High dose （80 mg·kg^-1） STZ injection can induce T2DM in mice, and low dose （20, 40 mg· kg^-1） and multiple injection can induce T1DM. The better dose is 40 mg·kg^-1.