摘要
目的探讨奥氮平对糖代谢的影响及其机制。方法将20只C57BL/6J雄性小鼠随机分成研究组和对照组,研究组小鼠每天给予奥氮平(5 mg/kg)灌胃,对照组按10 ml/kg灌注溶解奥氮平的柠檬酸溶剂。每天称量体质量,每周测量进食量,实验第3周及第6周时各测定1次腹腔葡萄糖耐量,实验第6周最后1天测定胰岛素耐量,并通过Westernblot方法检测肝脏蛋白Akt磷酸化水平。结果实验3周起研究组小鼠摄食量显著高于对照组(P<0.05),实验26 d起研究组小鼠体质量显著高于对照组(P<0.05)。实验6周时研究组小鼠空腹血糖显著高于对照组小鼠(P<0.05),研究组小鼠腹腔葡萄糖耐量曲线下面积显著高于对照组(P<0.05),此外胰岛素耐量实验也发现研究组小鼠胰岛素敏感性显著低于对照组(P<0.05)。研究组小鼠肝脏蛋白Akt磷酸化水平显著低于对照组(P<0.05)。结论长期奥氮平给药可以导致小鼠体质量和摄食增加、糖耐量异常和胰岛素抵抗,而胰岛素抵抗是由肝脏组织胰岛素信号通路中的重要蛋白Akt磷酸化下调所介导。
Objective To investigate the effect of olanzapine administration on glucose metabolism and to explore its mechanism.Methods 20 C57BL/6J mice were randomized into study group poured with intragastric olanzapine administration [5 rng/（kg·d）] and control group poured with intragastric olanzapine-citric acid dissolvent [10 rng/（kg·d）].Body weight was measured everyday and food-intake was measured every week.Celiac glucose tolerance was measured at the 3rd and the 6th week,and the insulin tolerance was measured at the last day of the 6th week.Western blot technology was used to detect the phosphorylation level of Akt hepatic protein.Results The average food-intake in study group was significantly higher than that in control group from the 3rd week of the study （P 〈 0.05）,the average body weight in study group was significantly higher than that in control group from the 26th day of the study （P 〈0.05）.At the 6th week of the study,level of fasting blood glucose in study group was significantly higher than that in control group （P 〈 0.05） and the AUC of Celiac glucose tolerance in study group was also significantly higher than that in control group （P 〈 0.05）.Insulin tolerance test showed that the insulin sensitivity in study group was significantly lower than that in control group （P 〈 0.05）.The phosphorylation level of Akt hepatic protein in study group was significantly lower than that in control group （P 〈 0.05）.Conclusion Long term olanzapine administration induces weight gain,hyperphagia,glucose tolerance abnormal and insulin resistance.The insulin resistance in olanzapine treated mice is due to the downregulation of Akt phosphorylation level which plays an important role in insulin signaling pathway in hepatic tissue.
出处
《精神医学杂志》
2013年第5期348-350,共3页
Journal of Psychiatry
