de la Garza-Rodea Anabel S, Knaän-Shanzer Shoshan, den Hartigh Jan D, Verhaegen Alphons P L, van Bekkum Dirk W
Virus and Stem Cell Biology Laboratory, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
J Am Assoc Lab Anim Sci. 2010 Jan;49(1):40-4.
Streptozotocin is widely used to induce diabetes in laboratory animals through multiple low-dose or single high-dose intraperitoneal injections. HPLC analysis has shown that the composition of the solution may change considerably during the first 2 h after dissolution due to equilibration of the 2 anomers (alpha and beta) of streptozotocin. Because of the drug's alleged instability in solution, the typical recommendation is to administer streptozotocin within 10 min after dissolution. We compared the induction of diabetes in NOD/SCID mice by injection of a single high dose of freshly made or anomer-equilibrated streptozotocin solution. Solutions were prepared from dry compound containing 85% of the alpha anomer, which is the more toxic of the 2. Body weight and nonfasting blood glucose levels were measured weekly for 8 wk. Both solutions induced long-term hyperglycemia, but blood glucose levels and mortality were higher and damage to pancreatic islands more pronounced in the mice receiving freshly prepared solution. A small proportion of mice did not respond in both treatment groups. If stored at 4 degrees C in the dark, the anomer-equilibrated solution retains its biologic activity for at least 40 d; under those conditions the streptozotocin content decreases by 0.1% daily, as determined by HPLC. Anomer-equilibrated streptozotocin solution has several practical advantages, and we recommend its use as standard for the induction of experimental diabetes because this practice may improve reproducibility and comparison of results between different laboratories.
链脲佐菌素广泛用于通过多次低剂量或单次高剂量腹腔注射在实验动物中诱导糖尿病。高效液相色谱分析表明，由于链脲佐菌素的两种异头物（α和β）达到平衡，溶液的成分在溶解后的前2小时内可能会发生相当大的变化。由于该药物据称在溶液中不稳定，典型的建议是在溶解后10分钟内给予链脲佐菌素。我们比较了注射单次高剂量的新鲜制备的或异头物平衡的链脲佐菌素溶液对NOD/SCID小鼠糖尿病的诱导情况。溶液由含有85%α异头物的干燥化合物制备，α异头物是两种中毒性更强的。每周测量8周的体重和非空腹血糖水平。两种溶液均诱导长期高血糖，但接受新鲜制备溶液的小鼠血糖水平和死亡率更高，胰岛损伤更明显。两个治疗组中都有一小部分小鼠没有反应。如果在4℃黑暗中储存，异头物平衡的溶液至少40天保持其生物活性；在这些条件下，通过高效液相色谱法测定，链脲佐菌素含量每天下降0.1%。异头物平衡的链脲佐菌素溶液有几个实际优点，我们建议将其用作诱导实验性糖尿病的标准制剂，因为这种做法可能会提高不同实验室结果的可重复性和可比性。
