完全脾切除增加了小鼠胰岛对STZ的敏感性

Splenectomy enhances sensitivity of islets to STZ in mice

目的:探讨脾脏对链脲菌素(STZ)损伤胰岛β细胞是否具有保护作用。方法:以外科手术切除小鼠全脾。60只脾切除小鼠随机分为3组,分别以80 mg/kg、160 mg/kg STZ给小鼠腹腔注射,另一组腹腔注射生理盐水。60只正常小鼠做同样分组及处理。1周后,测定各组小鼠空腹血糖、血清胰岛素水平,免疫组化分析各组胰岛β细胞总量,ELISA法分析胰岛细胞凋亡,Luminol化学发光法测定各组胰腺活性氧簇(ROS)水平。结果:80mg/kg STZ处理脾切除组空腹血糖浓度显著升高,血清胰岛素显著降低;同剂量STZ处理的正常小鼠血糖及胰岛素水平则正常;此外,80 mg/kg STZ处理的脾切除小鼠β细胞总量、胰岛凋亡细胞核小体聚集值及胰腺组织ROS的产生与同剂量STZ处理的正常小鼠相比均有显著差异。结论:脾可以阻止低剂量STZ对正常小鼠胰岛β细胞的破坏作用。完全脾切除增加了胰岛对STZ的敏感性,这一作用与胰腺组织ROS增加相关。

AIM：To explore the protective role of spleen in damage of islet beta cells induced by streptozotocin（STZ）.METHODS： Splenectomy in mice was performed by surgery.Sixty splenectomy mice were divided into 3 groups as the mice were intraperitoneally injected with STZ at doses of 80 mg/kg or 160 mg/kg,and saline,respectively.Sixty normal mice（without splenectomy） were also grouped and treated as above for controls.One week later,fasting blood glucose and serum insulin were monitored,and beta cell mass and the apoptosis of islet cells were analyzed by the methods of immunohistochemistry and ELISA,respectively.The content of reactive oxygen species was determined by the method of luminol-enhanced chemiluminescence.RESULTS： Compared to the normal control mice,the concentrations of fasting blood glucose significantly increased,and serum insulin reduced in splenectomy mice treated with STZ at the dose of 80 mg/kg.Moreover,beta cell mass decreased,enrichment factor of nucleosomes of islet apoptotic cells and reactive oxygen species produced in pancreas tissues significantly increased in splenectomy mice treated with STZ at the dose of 80 mg/kg.CONCLUSION： Splenectomy increases the sensitivity of islets to STZ in mice by increasing the production of reactive oxygen species in pancreas.