链脲菌素剂量对C57BL/6J小鼠糖尿病诱导效应的影响

目的 观察不同剂量链脲菌素(STZ)对C57BL/6J小鼠糖尿病诱导效应的影响,探讨其量效关系及最佳剂量范围.方法 将C57BL/6J小鼠按数字随机法分为9个STZ剂量组(A～I组,STZ分别为30、60、80、100、120、150、180、210、240 ms/kg体重),每组15只,腹腔注射;1个对照组,10只,腹腔注射等体积缓冲液.观察各组血糖、体重、血胰岛素和45 d生存率的变化,分析其与STZ剂量的关系.同时取A、C、G及对照组小鼠胰腺、肾脏组织做病理学检杏,并行免疫组化观察胰腺胰岛素及肾脏CD<,68>的表达.结果 C～G组较对照组血糖增高、体重及血胰岛素含量较对照组下降非常显著(P<0.05),且STZ剂量与血糖呈正相关(r=0.984,P<0.05),与血胰岛素含量呈负相关(r=-0.994,P<0.05).C～G组成模率达86.7%～100%,显著高于A、B组的0和40%(P<0.05);45 d生存率为46.7%～73.3%,显著高于H、I组的13.3%和0(P<0.05).A组胰腺、肾脏组织未见明显破坏;C组及G组出现典型的胰岛萎缩变形,胰岛素分泌颗粒减少,肾小球系膜外基质沉着及球周臣噬细胞浸润.结论 C57BL/6J小鼠腹腔注射STZ以80～180 mg/kg体重的剂量制模率高、生存率高,且靶器官损伤典型;该剂量与血糖呈正相关,与血胰岛素含量呈负相关.

Influence of streptozocin's dose on inductive effect of diabetes in C57BL/6J mice

Objective To investigate the influence of streptozocin (STZ)'s dose on the inductive effect of diabetes in C57BL/6J mice, and investigate the dose-effect relationship and the optimal dose range. Methods 145 C57BL/6J mice were randomly divided into 9 diabetic groups (group A to group 1, n = 15 in each group) and I control group (n = I0) to receive intraperitoneal injection of STZ with the dosages of 30, 60, 80, 100, 120, 150, 180, 210, 240 mg/kg and same amount of buffer solution,respectively. Changes of blood glucose, body weight, survival rate at 45 day and serum insulin level were monitored, and the relationship with STZ doses was analyzed. Pancreas and kidneys of the mice were removed for morphological examination, and immunohistochemistry was used for determination of insulin in pancreas and CD<,68> in kidneys. Results Compared with control group, blood glucose in group C ～G increased significantly; body weigh, insulin level decreased significantly (P < 0.05), and the STZ dose was positively correlated with mean blood glucose (r = -0.984, P < 0.05) and was negatively correlated with mean serum insulin levels (r = 0.994, P <0.05). The diabetes modeling rates in group C ～ G (86.7% ～ 100%) were higher than those of group A and B (0 and 40%, P<0.05). At the 45th day, the survival rates of group C ～G (46.7% ～ 73.3%) were higher than those of group H and 1 (13.3% and 0, P <0.05). There was no obvious injury of pancreas and kidneys in group B, whereas, in group C and G, pancreatic island atrophy and decreased insulin secretion were observed; deposits of extracellular matrix and macrophage increased in the mesangium were also present. Conclusions 80 ～ 180 mg/kg of STZ dose was ideal for establishing diabetes model in C57BL/6J mice. Within this range, the modeling rate and survival rate was higher, and target organs injury was typical. The STZ dose was positively correlated with blood glucose and negatively correlated with serum insulin levels.