恒河猴糖尿病动物模型血清及组织中细胞因子的变化

目的探讨恒河猴糖尿模型病细胞因子的水平和变化规律。方法健康恒河猴5只,小剂量(30mg/kg)多次静脉注射链脲佐菌素(STZ),血糖稳定后3、9、12和19个月检测血清中白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)的含量。安乐濒死状态的动物,取胰腺、肝脏、肾脏制成石蜡切片,用免疫组化染色法显示组织中IL-6、IL-10、TNF-α的表达,并对结果进行图像分析和统计学处理。结果造模后9个月动物血清中IL-10浓度显著降低(P<0.01)。IL-6、TNF-α水平在采样的各个时间点均显著高于造模前(P<0.01)。胰腺组织中IL-6中等强度着色,对照组弱阳性表达(P<0.05)。对照组IL-10强阳性表达,模型组弱阳性(P<0.01)。模型组TNF-α中等强度表达,对照组弱阳性(P<0.05)。模型组肝脏组织TNF-α中等阳性表达,对照组弱阳性(P<0.05)。结论小剂量多次注射STZ后恒河猴细胞因子的含量及变化与临床类似,可作为相关研究的动物模型。

Change of tissue and serum cytokine levels in rhesus monkey models of diabetes mellitus

Objective To investigate the changes of cytokines （IL-6, IL-10, TNF-α） in rhesus monkey models of diabetes mellitus. Methods Ten adult rhesus monkeys were divided into experimental and control groups, 5 in each group. The experimental monkeys were intravenously injected with streptozotocin （STZ） （30 mg/kg body weight, three times）. The dynamic changes of IL-6, IL-10 and TNF-α serum levels were measured for 19 months. The animals were sacrificed when impending death. The expressions of IL-6, IL-10 and TNF-α in the pancreatic islets, liver and kidney were examined by immunohistochemical staining. Image analysis and statistical analysis were carried out of all the data obtained above. Results Compared with the serum levels before STZ injection, the level of IL-10 was significantly increased （ P 〈 0.01 ）, while the levels of IL-6 and TNF-α decreased （P 〈0.01 ）. The expressions of IL-6 and TNF-α were significantly decreased in pancreatic islets than those in the control group （P 〈 O. 05 ）. The IL-10 expression was significantly increased in pancreatic islets than that in the control group （ P 〈 0. 01 ）. The number of TNF-α-positive cells in the liver was signifi- cantly decreased compared with that of the control group （ P 〈 0.05 ）. Conclusions The levels and changes of cytokines in the rhesus monkey models of diabetes mellitus generated by multiple injection of low-dose streptozotocin are similar to those in human diabetes, and this animal model may be used as a useful tool in researches assessing safety and efficacy of protective agents.