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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 the expression of glucose transporter 4 (GLUT4) gene in fasting blood glucose and skeletal muscle of male C57BL / 6 mice. Methods Sixty-three male C57BL / 6 mice were randomly divided into three groups (21 rats in each group): distilled water, clozapine 4 mg / kg and clozapine 20 mg / kg, After 4 weeks, the fasting blood glucose of each group was determined by the test strip method, and the GLUT4 mRNA expression was determined by reverse transcription polymerase chain reaction. Results (1) The fasting blood glucose and GLUT4 mRNA expression in clozapine 4 mg / kg group and clozapine 20 mg / kg group were not significantly different from those in blank control group 3 h and 1 week after irrigation (P> 0.05). (2) The fasting blood glucose of clozapine 4mg / kg group and 20mg / kg group were significantly higher than that of the control group [(5.6 ± 0.5) mmol / L and (5.8 ± 0.5) mmol / L] 4.6 ± 0.6) mmol / L], while the expression of GLUT4 mRNA (0.50 ± 0.14 and 0.48 ± 0.12) was lower than that of the blank control group (0.85 ± 0.27), the differences were statistically significant (P <0.01). Conclusion Clozapine can increase fasting blood glucose and decrease the expression of GLUT4 mRNA, which may be one of the mechanisms of antipsychotics after long-term application of hyperglycemia.