奥氮平诱导大鼠肥胖及其机制研究

目的建立奥氮平诱导的肥胖大鼠模型,并探讨其诱导肥胖的发生机制。方法 SD雌性大鼠20只,随机分为对照组和模型组,模型组大鼠每日黑暗时相前1h灌胃奥氮平(1.2mg/kg),对照组给予等容量蒸馏水。每周称体重1次,测饮水饮食量2次。给药7周时,利用SMART video-tracking system测定大鼠白天和黑暗时相的自主活动,然后处理大鼠,测体长,计算Lee's指数,称脂肪湿重,计算脂肪系数,采用高效液相色谱-电化学检测(HPLC-ECD)法测定大鼠下丘脑神经递质,用ELISA试剂盒测定血清瘦素(leptin)、脂联素(adiponectin,ADP)水平。结果模型组大鼠造模第2周至第7周时体重均明显高于对照组(P0.05或P0.01),饮食量明显增加(P0.01),黑暗时相平均速度、路程明显减少(P0.05),Lee's指数、脂肪湿重、脂肪系数明显升高(P0.05或P0.01),下丘脑5-HT、DA、DOPAC含量明显升高(P0.01或P0.05),血清leptin含量明显升高(P0.01),ADP含量明显降低(P0.01)。结论奥氮平(1.2mg/kg)增加动物摄食量,减少活动量而引起肥胖,此作用与下丘脑神经递质、瘦素和脂联素的调节有着密切联系。

Establishment of a Rat Model of Obesity Induced by Olanzapine and Its Development Mechanism

Objective To establish an obesity model induced by olanzapine in rats and to investigate its development mechanism.Methods Twenty female Sprague-Dawley rats were randomly divided into two groups：control group and model group.The model group was given olanzapine （OLAN,1.2 mg/kg,q.d.） via gavage 1 h before the beginning of the dark-phase.Body weight was recorded each week and the amount of food and water intake was checked twice a week.After 7 weeks＇ administration of OLAN,spontaneous activity was monitored continuously using the SMART video-tracking system during the light and dark phases.The naso-anal length and the fat weight of each rat were recorded.Lee＇s index and coefficient of fat were calculated.Hypothalamic neurotransmitters were measured by high performance liqiud chromatography coupled with electrochemical detector （HPLC-ECD）.The levels of serum leptin and ADP were determined with an ELISA kit.Results Compared with the control rats,the body weight of model rats was significantly increased during the second week to the seventh week of OLAN treatment （P0.05 or P0.01）,the average speed and distance of movement during the dark phase were decreased significantly （P0.05）,food intake,Lee＇s index,fat weight and coefficient of fat were increased significantly （P0.05 or P0.01）,the contents of 5-HT,DA,DOPAC in hypothalamus were increased significantly （P0.05 or P0.01）,the level of serum leptin was increased and the content of serum ADP was decreased significantly （P0.01）.Conclusions A rat model of obesity is successfully established with OLAN （1.2 mg/kg） administration.It seems that the obesity is developed through increasing food intake and reducing spontaneous activity,and may be closely ralated with regulations of leptin,ADP and neurotransmitters in the hypothalamus.