第二代抗精神病药对大鼠血糖、胰岛素和C肽分泌的影响

目的 了解第二代抗精神病药(氯氨平、奥氮平、喹硫平、阿立哌唑)对大鼠体重、空腹血糖、胰岛素和C肽分泌的影响.方法 25只雌性SD(Sprague Dawley,SD)大鼠随机均分成5组.分别给予氯氮平20 mg/(kg·d)、奥氮平5 mg/(kg·d)、喹硫平20 mg/(kg·d)、阿立哌唑5mg/(kg·d)和生理盐水灌胃,共28 d.在第1、7、14、28天分别剪尾采血,测体重及空腹血糖,于第28天测定空腹血浆胰岛素和C肽水平.结果 适应性喂养1周后,5组大鼠的空腹血糖和体重水平差异无统计学意义(P＞0.05).持续灌胃第14及28天,氯氮平、奥氮平和喹硫平组空腹血糖高于空白时照组(P＜0.05)；持续灌胃28 d,氯氮平、奥氮平组的体重高于空白对照组(P＜0.05)；与未加处理因素前(第1天)相比,氯氮平、奥氮平和喹硫平组体重和空腹血糖随时间的延长而增加(P＜0.05),而阿立哌哇组的变化无统计学意义(P＞0.05).持续灌胃第28天,氯氮平、奥氮平和喹硫平组空腹血浆胰岛素和C肽水平高于空白对照组(P＜0.05)；而阿立哌唑组变化不明显(P＞0.05).结论 氯氮平、奥氮平、喹硫平可引起大鼠胰岛素抵抗和血糖代谢异常.

Effects of second generation antipsychotics on blood glucose,insulin, and C-peptide in rats

Objective To study the effects of second generation antipsychotlcs on body weight, blood glucose,insulin, and C-peptide in rats. Methods Twenty-five female SD rats were randomly divided into five groups. The rats in each group were intragastrically administrated clozapine 20 mg/（kg · d）, olanzapine 5 mg/（kg · d）, quetiapine 20 mg/（kg · d）, ariprazole 5 mg/kg/d and normal saline for 28 days. The blood glucose and body weight were measured at the l st,7th, 14th and 28th day. The level of serum insulin and C--peptide were measured with immunoradiometric assay method at the 28th day. Results The levels of blood glucose in clozapine, olanzapine and quetiapine treated groups were higher than that in control group （P 〈 0.05） at day 14 and 28. The levels of body weight in clozapine and olanzapine treated groups were higher than those in control group （P〈0.05） at the 28th day. The levels of serum insulin and C-peptide in clozapine,olanzapine and quetiapine treated groups were higher than those in control group （P 〈 0.05）. Conclusions Clozapine,olanzapine and quetiapine can increase the level of blood glucose via the mechanism of insulin resistance.