不同剂量STZ诱导小鼠糖尿病模型的发病机制

doi:教育部归国人员启动基金资助课题（2002）

不同剂量STZ诱导小鼠糖尿病模型的发病机制

杨巍¹，罗春元¹，于春雷¹，王莉¹，许丽芳²，李一^1*

1. 吉林大学基础医学院免疫学教研室，吉林长春130021；2. 吉林大学第一医院儿科特诊室，吉林长春130021

收稿日期:2005-06-07 修回日期:1900-01-01 出版日期:2006-05-28 发布日期:2006-05-28
通讯作者: 李一

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

YANG Wei¹, LUO Chun-yuan¹, YU Chun-lei¹, WANG Li¹, XU Li-fang², LI Yi^1*

1. Department of Immunology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China;2. Department of Pediatrics, First Hospital, Jilin University, Changchun 130021, China

Received:2005-06-07 Revised:1900-01-01 Online:2006-05-28 Published:2006-05-28
Contact: LI Yi

摘要/Abstract

摘要： 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。

关键词: 糖尿病, 实验性, 自身抗体, T淋巴细胞

Abstract: 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 Forty 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 Tlymphocytes in mouse spleen and thymus were detected by Lymphocytes Proliferation Assay (MTT method). Results The blood glucose in group Ⅰ changed 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 group Ⅱ 5 negative and others >+, in group Ⅲ 2 negative and others >++, in group Ⅳ all >+++. The changes and degrees of pancreatic islet β cells injured by difference doses of STZ were different. The IAA levels in groupⅡand 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 Con A in groupⅡand Ⅲ. However, there was no difference between group Ⅳ and 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.

Key words: diabetes mellitus, experimental, autoantibodies, T-lymphocytes

中图分类号:

R-332

杨巍，罗春元，于春雷，王莉，许丽芳，李一. 不同剂量STZ诱导小鼠糖尿病模型的发病机制[J]. J4, 2006, 32(3): 432-435.

YANG Wei, LUO Chun-yuan, YU Chun-lei, WANG Li, XU Li-fang, LI Yi. Pathogenesis of mouse diabetes mellitus models induced by different doses of streptozotocin[J]. J4, 2006, 32(3): 432-435.

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