小型猪2型糖尿病模型的部分血清炎性因子变化

Changes of Some Serum Inflammatory Cytokines in Type 2 Diabetes Model of Minipigs

目的动态观察小型猪2型糖尿病(T2DM)模型血清中炎性因子水平,为2型糖尿病研究提供参考资料。方法将10头巴马小型猪随机分为对照组(Control)和模型组(DM),对照组以常规饲料喂养,模型组以高脂饮食联合静脉注射链脲佐菌素(STZ)建立小型猪2型糖尿病模型。实验为期9个月,每月检测动物空腹血糖与胰岛素水平,每3个月检测一次糖耐量。采用ELISA试剂盒检测第0、3、6、9个月动物血清中的11种炎性因子水平。结果在高脂饮食诱导3个月后注射STZ,模型组空腹血糖显著升高(P<0.05),糖耐量严重受损,发生了胰岛素抵抗。ELISA结果显示,模型组与对照组动物血清中11种炎性因子水平在前3个月并无特别大的变化,且两组对比无统计学意义。在T2DM发病后,模型组血小板衍生生长因子-BB(PDGF-BB)和肿瘤坏死因子α(TNF-α)的表达水平升高并显著高于对照组(PDGF-BB,第6个月P<0.05;PDGF-BB、TNF-α,第9个月P<0.05),模型组白细胞介素-6(IL-6)的表达水平随着时间的增加逐渐升高,在第9个月的表达水平显著高于第0、3个月(P<0.05),但是与对照组对比并无显著性差异。结论采用高脂饲料联合低剂量STZ成功建立了小型猪2型糖尿病模型。单纯高脂饮食未对小型猪血清炎性因子水平造成明显影响,在T2DM发病后PDGF-BB和TNF-α在血清中的表达水平升高且显著高于正常动物。

Objective To dynamically observe the levels of inflammatory cytokines in the serum of type 2 diabetes(T2DM)model in miniature pigs,so as to provide reference data for the study of type 2 diabetes.Method Ten Bama minipigs were randomly divided into a Control group and a model group(DM).The Control group was fed with conventional diet,and the DM model in miniature pigs was established by high-fat diet combinated with intravenous streptozotocin(STZ).The experiment lasted for nine months,fasting blood glucose and insulin were measured monthly,and glucose tolerance was measured every 3 months.Concentrations of 11 inflammatory cytokines in serum of animals at the 0th,3rd,6th,and 9th months were determined by ELISA kit.Result The fasting blood glucose was significantly increased(P<0.05),severely impaired of glucose tolerance and insulin resistance occurred in the DM group after high-fat diet for 3 months injected with STZ.The ELISA result showed that there was no significant change in the levels of 11 inflammatory cytokines of the DM group at the first 3 months,and no significant difference compared to the Control group.The levels of platelet-derived growth factor-BB(PDGF-BB)and tumor necrosis factor-α(TNF-α)were increased after the onset of T2DM and significantly higher than those of in Control group(PDGF-BB,P<0.05 at the 6th month;PDGF-BB and TNF-α,P<0.05 at the 9th month).The level of interleukin-6(IL-6)in the DM group was increased gradually over time which the level at the 9th month was significantly higher than that at the 0th and 3rd month(P<0.05),but no significant difference compared with the Control group.Conclusion The model of type 2 diabetes in minipigs was successfully established by using high-fat diet combined with low-dose STZ.A simply high-fat diet was not obvious influence on the levels of inflammatory cytokines in serum of mini-pigs,whereas the levels of PDGF-BB and TNF-αin serum of T2DM mini-pigs were significantly increased and higher than those in normal animals.