外源性高糖对脾切除小鼠血糖的影响及其机制探讨

Effect of exogenous high glucose on blood glucose of splenectomy mice and its mechanism

目的探讨持续外源性葡萄糖干预是否影响胰岛β细胞的内分泌功能,以及脾脏是否也参与该过程。方法外科手术切除小鼠全脾。将实验小鼠分为8组,分别以不含葡萄糖的纯水及10%、15%和20%葡萄糖饮水喂养正常(4组)和脾切除小鼠(4组)3周。测定小鼠空腹血糖和胰岛素水平,计算各组小鼠高血糖发生率;进行胰岛素释放试验、胰岛组织免疫组织化学双染色、胰腺组织活性氧簇(ROS)测定及胰岛β细胞葡萄糖转运体-2(GLUT-2)表达分析。结果 20%葡萄糖饮水喂养的正常组和脾切除组小鼠出现高血糖,发生率分别为60%和75%;所有高血糖小鼠胰岛素释放能力降低,出现胰岛β细胞凋亡。脾切除组高血糖小鼠,胰岛β细胞ROS水平升高,GLUT-2表达水平降低更加显著。结论脾脏参与外源性高糖对胰岛内分泌功能损伤的保护作用涉及胰岛β细胞ROS和GLUT-2表达水平的改变。

[Objective] To explore the impact of exogenous glucose intervention on the endocrine function of islet β cells and the possible participation of the spleen in this process. [Methods] Spleneetomy was per- formed in mice. The mice were divided into 8 groups including 4 normal groups and 4 splenectomy groups, which were fed with glucose-free water, 10%, 15% or 20% glucose drinking water respectively for 3 weeks. Fasting plasma glucose and insulin levels were determined in the mice. The incidence of hyperglycemia of each group was calculated. Insulin release test, double immunohistochemical staining of the islet tissue, analy- ses of reactive oxygen species （ROS） in pancreatic tissue and glucose transporter-2 （GLUT-2） expression in cells were conducted. [Results] Hyperglycemia was induced in the normal and splenectomy mice fed with 20% glucose drinking solution; the incidence was 60% and 75% respectively. The insulin release capacity significantly reduced and apoptosis of the islet β cells occurred in all the hyperglycemic mice. ROS level in the pancreas tissue and the level of GLUT-2 expression changed more significantly in the hyperglycemic mice with splenectomy. [Conclusions] The spleen is involved in protection of the islet endocrine function from damage caused by exogenous glucose intervention. This process relates to increased ROS level and decreased GLUT-2 expression in the islet β cells.