不同浓度氯氮平对小鼠空腹血糖和骨骼肌葡萄糖转运蛋白4基因表达的影响  

Effects of clozapine on fasting blood glucose and mRNA expression of skeletal muscle glucose transporter 4 in male mice

作　　者：成为荣[1] 谢世平[1] 张向荣[1] 张志珺[2] 

机构地区：[1]南京医科大学附属脑科医院精神科,210029 [2]东南大学附属南京中大医院神经内科

出　　处：《中华精神科杂志》2006年第4期224-227,共4页Chinese Journal of Psychiatry

摘　　要：目的探讨氯氮平对雄性C57BL/6小鼠空腹血糖和骨骼肌葡萄糖转运蛋白4(GLUT4)基因表达的影响。方法将63只雄性C57BL/6小鼠随机分为3组,每组21只,分别灌胃给予蒸馏水、氯氮平4mg/kg及氯氮平20mg/kg,于给药后3h、1周、4周以试纸法测定各组空腹血糖,用逆转录-聚合酶链反应测定GLUT4mRNA表达。结果(1)灌药后3h、1周氯氮平4mg/kg组和氯氮平20mg/kg组空腹血糖和GLUT4mRNA的表达与空白对照组相比,差异无统计学意义(P>0.05);(2)灌药后4周氯氮平4mg/kg组和20mg/kg组的空腹血糖值[(5.6±0.5)mmol/L和(5.8±0.5)mmol/L]高于空白对照组[(4.6±0.6)mmol/L],而GLUT4mRNA的表达(0.50±0.14和0.48±0.12)却低于空白对照组(0.85±0.27),差异均有统计学意义(P<0.01)。结论氯氮平可以慢性升高空腹血糖,降低GLUT4mRNA的表达,可能是抗精神病药长期应用后血糖升高的发生机制之一。Objective To investigate the effects of clozapine on fasting blood glucose and mRNA expression of skeletal muscle glucose transporter gene 4 （GLUT4） in the male mice. Methods Sixty-three male C57BL/6 mice were randomly divided into three groups （21 in each）, which were treated with clozapine4 mg/kg, clozapine 20 mg/kg or vehicle （distilled water） respectively once daily by gavage. Seven mice in each group were selected after three hour, one week and four week treatment respectively for measuring the fasting blood glucose and GLUT4 mRNA expression with the reverse transcription-polymerase chain reaction （RT-PCR）. Results There was no significant difference between the three groups in fasting blood glucose and GLUT4 mRNA expression （ P 〉 0.05 ） after 3 hour and 1 week treatment with clozapine. The fasting blood glucose was significantly higher and GLUT4 mRNA expression was significantly lower in clozapine 4 mg/kg group and clozapine 20 mg/kg group than that in controls after 4 week treatment （ P 〈 0. 01 ）. Conclusion Clozapine may increase blood glucose and decrease GLUT4 mRNA expression after long-term treatment. The down-regulation of GLUT4 mRNA possibly plays a role in the elevation of blood glucose induced by clozapine.

关 键 词：氯氮平 血糖 单糖转运蛋白质类 小鼠 近交C57BL 

分 类 号：R96[医药卫生—药理学]