奥氮平诱导性肥胖大鼠糖、脂代谢紊乱及其影响机制研究  

Glucose and lipid metabolism disorder in olanzapine-induced obesity rats and its influencing mechanism

作　　者：褚留杰[1] 谷争 韩亚琼[1] 张瑞岭[2] Chu Liujie;Gu Zheng;Han Yaqiong;Zhang Ruiling(Department of Pharmacy,The Second Affiliated Hospital of Xinxiang Medical College;Department of Psychiatry,The Second Affiliated Hospital of Xinxiang Medical College)

机构地区：[1]新乡医学院第二附属医院药学部,新乡453002 [2]新乡医学院第二附属医院精神科,新乡453002

出　　处：《重庆医科大学学报》2020年第3期368-371,共4页Journal of Chongqing Medical University

基　　金：河南省卫生科技创新型人才工程专项资助项目(编号:2011-2015第3052号)。

摘　　要：目的:探究奥氮平诱导大鼠的糖、脂代谢紊乱及其影响机制。方法:按照随机数字表法,将40只健康成年雄性大鼠分为对照组与观察组,每组各20只,其中对照组采用常规饲养模式,观察组在常规饲养的基础上,增加灌胃奥氮平(1.2 mg/kg),连续4周。比较4周后2组大鼠的体质量、血糖、血脂等指标的变化,并测定胰腺中糖代谢关键基因葡萄糖激酶(glucokinase,GCK)、葡萄糖转运蛋白-2(glucose transporter-2,GLUT-2),脂肪细胞中关键基因过氧化物酶体增殖物激活受体-γ(peroxisome proliferator activated receptor-γ,PPARγ)和脂肪酸合成酶(fatty acid synthase,FAS)的表达水平。结果:实验4周后,观察组的体质量超过对照组23%,并且从第2周开始,观察组体质量明显高于对照组(P<0.05);观察组的空腹血糖、总胆固醇、甘油三酯、低密度脂蛋白(low density lipoprotein,LDL)均明显高于对照组(P<0.05),但其高密度脂蛋白(high density lipoprotein,HDL)低于对照组(P<0.05)。观察组的GCK、GLUT-2基因mRNA表达水平明显低于对照组(P<0.05),而其PPARγ、FAS基因mRNA表达水平明显高于对照组(P<0.05)。结论:奥氮平能够引起大鼠机体的糖、脂代谢紊乱,其机制可能与下调糖代谢关键基因GCK、GLUT-2,上调脂肪细胞分化关键基因PPARγ、FAS有关。Objective:To investigate the disorder of glucose and lipid metabolism induced by olanzapine in rats and its influencing mechanism.Methods:According to the random digits table method,40 healthy adult male rats were divided into the control group and the observation group,with 20 rats in each group.Rats in the control group were received normal food,while in the observation group were fed with olanzapine(1.2 mg/kg)on the basis of normal food for continuous four weeks.After four weeks,indicator changes of body weight,glycemia and lipidemia were compared.Additionally,pancreatic glycometabolism key kinase of glucokinase(GCK)and glucose transporter-2(GLUT-2),and lipocytes key kinase of peroxisome proliferator activated receptor-γ(PPARγ)and fatty acid synthase(FAS)were measured.Results:After four weeks,the weight of rats in the observation group was 23%higher than that in the control group,and the weight of rats in the observation group was significantly higher than that in the control group from the second week(P<0.05);fasting glucose,total cholesterol,triglyceride and low density lipoprotein(LDL)of rats in the observation group were significantly higher than those in the control group(P<0.05),but the high density lipoprotein(HDL)of rats in the observation group was lower than that in the control group(P<0.05).The mRNA expression levels of GCK and GLUT-2 in the observation group were significantly lower than those in the control group(P<0.05),while the mRNA expression levels of PPARγand FAS genes were significantly higher than those in the control group(P<0.05).Conclusion:Olanzapine can induce the disorder of glucose and lipid metabolism in rats,and its mechanism may be related to the downregulating key glycometabolic genes of GCK and GLUT-2,and the upregulating lipocytes differentiation key genes of PPARγand FAS.

关 键 词：奥氮平 肥胖 糖代谢紊乱 脂代谢紊乱 

分 类 号：R114[医药卫生—卫生毒理学]