【摘要】 目的 探索不同剂量奥氮平对小鼠代谢的影响及饥饿素（Ghrelin）的中介效应。方法将SPF级雄性C57BL/6小鼠40只，随机分为对照组（CG,0.2 mL生理盐水灌胃）、奥氮平低剂量组（LG,0.5 mg/kg奥氮平灌胃）、奥氮平中剂量组（MG,1.0 mg/kg奥氮平灌胃）和奥氮平高剂量组（HG,2.0 mg/kg奥氮平灌胃），每组10只，比较实验前后小鼠各指标的变化。结果 四组小鼠体重的差异不显著（P=0.141）。四组小鼠摄食量的差异有统计学意义（P=0.004）,CG组、HG组摄食量显著高于LG组和MG组。四组小鼠活动总路程的差异有统计学意义（P<0.001）,CG组和LG组总路程显著高于MG组和HG组。四组小鼠在血浆总胆固醇（TC）水平变化上差异有统计学意义（P=0.003）,CG组显著低于其他三组。四组小鼠实验前后的甘油三酯（TG）差异有统计学意义（P<0.001）,CG组TG显著低于其他三组。四组小鼠实验前后的低密度脂蛋白（LDL-C）差异有统计学意义（P=0.014）,CG组LDL-C显著低于其他三组。四组小鼠实验前后的高密度脂蛋白（HDL-C）差异不显著（P=0.164）。四组小鼠实验前后的Ghrelin差异有统计学意义（P<0.001）,MG组Ghrelin显著高于CG组和LG组，HG组Ghrelin显著高于其他三组。路径分析结果显示，Ghrelin对体重（BW）无显著影响（P=0.991）;Ghrelin对TG存在显著正向影响（P<0.001）;Ghrelin对TC存在显著正向影响（P=0.001）;Ghrelin对LDL-C存在显著正向影响（P<0.043）;Ghrelin对HDL-C无显著影响（P=0.539）。结论 短时间内服用0.5 mg/kg和1.0 mg/kg奥氮平的小鼠食物摄入量减少；奥氮平可明显升高血脂水平，且影响结果无明显剂量依赖性；1.0 mg/kg和2.0 mg/kg奥氮平降低了小鼠的活跃程度；0.5 mg/kg、1.0 mg/kg和2.0 mg/kg奥氮平均升高了血浆TC、TG和LDL-C水平，只有1.0 mg/kg和2.0 mg/kg奥氮平升高了血浆Ghrelin水平。Ghrelin介导了奥氮平对小鼠脂代谢影响的过程。更多还原

【Abstract】 Objective To explore the effects of different doses of olanzapine on metabolism and the mediating effects of Ghrelin. Methods Forty SPF male C57BL/6 mice were randomly divided into control group(CG,0.2 mL normal saline gavage),olanzapine low-dose group(LG,0.5 mg/kg olanzapine gavage),olanzapine medium-dose group(MG,1.0 mg/kg olanzapine gavage)and olanzapine high-dose group(HG,2.0 mg/kg olanzapine),10 mice in each group. The changes of each index were compared before and after the experiment. Results There was no significant difference in body weight among the four groups(P=0.141). The food intake of the four groups was significantly different(P=0.004),and the food intake of the CG and HG groups was significantly higher than that of the LG and MG groups.The difference of the total distance of the four groups was statistically significant(P<0.001),the total distance of CG and LG groups was significantly higher than that of MG and HG groups. The difference of TC level in the four groups was statistically significant(P=0.003),and the CG group was significantly lower than the other three groups. The TG levels of the four groups were significantly different before and after the experiment(P<0.001),TG of CG group was significantly lower than that of the other three groups. LDL-C of the four groups was significantly different before and after the experiment(P=0.014),and LDL-C of the CG group was significantly lower than that of the other three groups. There was no significant difference in HDL-C between the four groups before and after the experiment(P=0.164). There were significant differences in Ghrelin between the four groups(P<0.001),the Ghrelin in MG group was significantly higher than that in CG and LG groups,and the Ghrelin in HG group was significantly higher than that in the other three groups.Ghrelin had a significant positive effect on TG(P<0.001),TC(P=0.001)and LDL-C(P<0.043),while Ghrelin had no significant effect on HDL-C(P=0.539). Conclusion Short-term administration of 0.5 mg/kg and 1.0 mg/kg olanzapine can significantly reduce the food intake of mice. Olanzapine can significantly increase the blood lipid level,and the effect of dose dependence is not obvious.1.0 mg/kg and 2.0 mg/kg olanzapine decreased the activity level of mice;On average,0.5 mg/kg,1.0 mg/kg and 2.0 mg/kg olanzapine increased plasma TC,TG and LDL-C levels,while only 1.0 mg/kg and 2.0 mg/kg olanzapine increased plasma Ghrelin levels. Ghrelin mediated the process of olanzapine on lipid metabolism in mice.更多还原