摘要
目的研究长效胰岛素重组甘精胰岛素对小鼠神经系统的影响和对犬的免疫原性。方法选取小鼠40只,随机分为重组甘精胰岛素注射液大剂量组、中剂量组、小剂量组和溶剂对照组,每组10只,均皮下注射给药,测定小鼠行为活动、激怒反应、爬竿运动及自主活动的变化。将24只Beagle犬随机分为重组甘精胰岛素注射液大、中、小剂量组及溶剂对照组,每天皮下注射给药1次,连续3个月,观察犬的免疫毒性和免疫原性。结果大、中、小剂量的重组甘精胰岛素注射液皮下注射给药后,小鼠步态活动(每分钟在实验台的活动距离)有明显改变,给药后30min及60min步态活动减少,翻正反射降低,攻击和逃避反应差,自主活动减弱,激怒反应减弱。给药前后犬的淋巴细胞分类百分数、淋巴细胞绝对值比较无统计学意义,未检测到血清抗体;免疫器官脾脏、胸腺、淋巴结病理组织学检查均未见明显异常。结论重组甘精胰岛素对正常小鼠的神经系统有抑制作用,对犬无免疫原性。
Objective To study the impact of long- acting recombinant insulin glargine on the nervous system in mice and its immunogenicity in dogs. Methods 40 mice, half male and female, were randomly divided into the recombinant insulin glargine groups with large dose, middle dose and small dose groups and solvent control group, 10 cases in each group. To study the behavior test, angered response, pole- climbing and self- movement activities in mice. The 24 Beagle dogs were randomly divided into 4 groups with insulin glargine injection of large, middle and small dose recombinant insulin glargine, once daily for 3 months. The immunotoxicity and immunogenicity were observed in Beagle dogs. Results In the mice with subcutaneous administration of large, middle and small-dose recombinant insulin glargine, after administration of 0. 5 h and 1 h, the animals gait activities （activities distance per minute in the experimental stage） signifi- cantly reduced and slowed, righting reflex reduced, poor response to attacks and to avoid, self-activity weakened, diminished response to anger. The classification percentage of lymphocytes and absolute lymphocytes in the dogs before and after administration showed no statistical significance. No serum antibodies against glargine were detected. The pathological examination of immune organs spleen, thymus and lymph nodes had no obvious abnormalities. Conclusion Recombinant insulin glargine has the inhibitive effect on the nervous system of normal mice and has no immunogenicity on dogs.
出处
《中国药业》
CAS
2010年第7期14-15,共2页
China Pharmaceuticals
