奥氮平诱导雄性大鼠产生胰岛素抵抗的机制研究  

Mechanism of olanzapine-induced insulin resistance in male rats

作　　者：吕一帆 刘守青 张倩倩 彭世勇 杨妮 李士红 黎维勇 LYU Yi-fan;LIU Shou-qing;ZHANG Qian-qian;PENG Shi-yong;YANG Ni;LI Shi-hong;LI Wei-yong(Institute of Psychiatry and Neuroscience,Xinxiang Medical University,Xinxiang 453000,Henan Province,China;Department of Pharmacy,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,Hubei Province,China)

机构地区：[1]新乡医学院精神与神经医学研究院,河南新乡453000 [2]华中科技大学同济医学院附属协和医院药剂科,湖北武汉430022

出　　处：《新乡医学院学报》2019年第12期1105-1109,共5页Journal of Xinxiang Medical University

基　　金：国家自然科学基金资助项目(编号:81573509)

摘　　要：目的探讨奥氮平诱导雄性Sprague Dawley(SD)大鼠产生胰岛素抵抗的机制。方法将20只雄性SD大鼠随机分为对照组和奥氮平组,每组10只;奥氮平组大鼠每日给予1.5 mg·kg^-1奥氮平灌胃,对照组大鼠给予等量生理盐水灌胃,连续8周。于给药前及给药后第1~8周测2组大鼠空腹血糖(FBG),并记录大鼠体质量。给药后2、4、6、8周取大鼠尾静脉血,采用酶联免疫吸附试验法(ELISA)检测血浆胰岛素水平,并计算胰岛素抵抗指数(HOMA-IR);给药后第8周,行口服糖耐量实验(OGTT);并于给药后第8周末取大鼠白色脂肪组织及大脑前额叶皮质,Western blot法检测2组大鼠白色脂肪组织中早期生长反应因子-1(Egr-1)、香叶基香叶基二磷酸合成酶(GGPPS)、胰岛素受体底物-1(IRS-1)蛋白表达水平,ELISA检测2组大鼠白色脂肪组织及大脑前额叶皮质中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6水平。结果给药前2组大鼠体质量比较差异无统计学意义(P>0.05);给药后第1~8周,2组大鼠体质量均呈稳定上升,但2组大鼠体质量比较差异无统计学意义(P>0.05)。给药前及给药后1~2周,2组大鼠FBG比较差异无统计学意义(P>0.05);给药后3~8周,奥氮平组大鼠FBG高于对照组(P<0.05);给药后第2、4、6、8周,奥氮平组大鼠胰岛素水平、HOMA-IR高于对照组(P<0.05)。奥氮平组和对照组大鼠OGTT曲线下面积分别为932.4±51.5和762.8±90.7,奥氮平组大鼠OGTT曲线下面积大于对照组(P<0.05);奥氮平组大鼠白色脂肪组织中Egr-1、GGPPS、IRS-1蛋白相对表达量高于对照组(P<0.05)。奥氮平组大鼠白色脂肪组织中TNF-α、IL-1β和IL-6水平高于对照组(P<0.05)。2组大鼠大脑前额叶皮质中TNF-α、IL-1β和IL-6水平比较差异无统计学意义(P>0.05)。结论奥氮平可诱导雄性SD大鼠产生胰岛素抵抗,且胰岛素抵抗的形成可能与白色脂肪组织中Egr-1、GGPPS、IRS-1和炎性因子水平显著增高有关。Objective To investigate the mechanism of olanzapine-induced insulin resistance in male Sprague Dawley(SD)rats.Methods Twenty male SD rats were randomly divided into control group and olanzapine group,with 10 rats in each group.Rats in the olanzapine group were given 1.5 mg·kg^-1 olanzapine daily by gavage,and the rats in the control group were given the same amount of physiological saline for 8 weeks continuously.The fasting blood glucose(FBG)levels of rats in the two groups were measured before and at 1-8 weeks after administration,and their body mass was recorded.Venous blood was taken from the tail of rats at 2,4,6 and 8 weeks after administration,and the plasma insulin levels were detected by enzyme-linked immunosorbent assay,and homeostasis model assessment-insulin resistance index(HOMA-IR)was calculated.Oral glucose tolerance test(OGTT)was performed at 8 weeks after administration.White adipose tissue and prefrontal cortex of rats were taken at 8 weeks after administration.The expressions of early growth response factor-1(Egr-1),geranylgeranyl diphosphate synthase(GGPPS),insulin receptor substrate-1(IRS-1)protein in the white adipose tissue of rats in the control group and the olanzapine group were determined by Western blot.The levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1βand IL-6 in the prefrontal cortex of the brain and white adipose tissue of rats in the two groups were examined by enzyme-linked immunosorbent assay.Results There was no significant difference in body mass between the two groups before administration(P>0.05).After 1-8 weeks of administration,the body mass of rats in the two groups increased steadily,but there was no significant difference between the two groups(P>0.05).There was no significant difference in the FBG level between the two groups before and at 1-2 weeks after administration(P>0.05).At 3-8 weeks after administration,the FBG level in the olanzapine group was higher than that in the control group(P<0.05).At 2,4,6 and 8 weeks after administration,the insulin l

关 键 词：奥氮平 胰岛素抵抗 早期生长反应因子-1 香叶基香叶基二磷酸合成酶 胰岛素受体底物-1 

分 类 号：R749[医药卫生—神经病学与精神病学]