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背景:抗精神病药物可引起血糖升高甚至导致2型糖尿病。二甲双胍可能会减轻上述副作用。目的:评价二甲双胍能否减轻使用抗精神病药氯氮平时发生的糖代谢异常。方法:将18只成年SD大鼠分为3组,分别用生理盐水、氯氮平(20mg/kg)及氯氮平(20mg/kg)+二甲双胍(78mg/kg)灌胃28d。在基线及其后每隔7天测空腹血糖。实验第28d麻醉大鼠使其安乐死,此时取腹主静脉血,用放射免疫法检测血胰岛素和C肽水平;取胰腺组织,采用实时聚合酶链反应和Western Blot技术检测葡萄糖转运体2(glucose transporter-2,GLUT2)的表达水平。结果:氯氮平组第14天、21天和28天的空腹血糖值均显著高于基线值,但氯氮平+二甲双胍组仅第14天时的空腹血糖值较基线明显升高。尽管如此,重复测量的方差分析并未发现三组间随时间变化的血糖水平差异有统计学意义(p=0.136)。多组比较发现氯氮平+二甲双胍组的胰岛素均值显著低于盐水组及氯氮平组。组间GLUT2mRNA的表达差异具有统计学意义(氯氮平+二甲双胍组<氯氮平组<盐水组),组间GLUT2蛋白的表达差异亦有统计学意义(氯氮平+二甲双胍组,氯氮平组<盐水组)。结论:本研究发现氯氮平一定程度上能使SD大鼠空腹血糖水平升高,联合使用二甲双胍可部分抵消血糖的升高。正如预期,接受氯氮平的SD大鼠GLUT2的表达水平降低。然而,意料之外的是氯氮平联合二甲双胍治疗28 d并未使GLUT2的表达水平正常化。
Background: Antipsychotics cause elevated blood sugar and even cause type 2 diabetes. Metformin may reduce these side effects. PURPOSE: To evaluate whether metformin can reduce the abnormal glucose metabolism during the use of the antipsychotics clozapine. Methods: Eighteen adult SD rats were divided into three groups and were given gavage for 28 days with normal saline, clozapine (20mg / kg) and clozapine (20mg / kg) and metformin (78mg / kg) respectively. Fasting blood glucose was measured at baseline and every 7 days thereafter. At the 28th day, the rats were anesthetized and euthanized. At this time, the abdominal venous blood was taken and the levels of blood insulin and C-peptide were measured by radioimmunoassay. The pancreatic tissues were taken for real-time polymerase chain reaction and Western Blot to detect the glucose transporter 2 ( glucose transporter-2, GLUT2) expression levels. Results: The fasting blood glucose values of the clozapine group on day 14, day 21 and day 28 were significantly higher than the baseline values. However, the fasting blood glucose level of clozapine + metformin group was significantly higher than baseline on the 14th day. However, repeated measures ANOVA did not find significant differences in blood glucose levels over time among the three groups (p = 0.136). Multiple groups found that the average insulin level of clozapine + metformin group was significantly lower than that of saline group and clozapine group. There were significant differences in the expression of GLUT2mRNA among the groups (clozapine + metformin group
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