引用本文:曾晏萍, 胡钟艺, 陈小英, 胡昌华, 刘雪梅.短期氟哌啶醇、利培酮、阿立哌唑作用对小鼠糖脂代谢及行为学影响[J].西南大学学报(自然科学版),2019,41(12):40~49
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短期氟哌啶醇、利培酮、阿立哌唑作用对小鼠糖脂代谢及行为学影响
曾晏萍, 胡钟艺, 陈小英, 胡昌华, 刘雪梅
西南大学 药学院, 重庆 400715
摘要:
探究不同抗精神病药物(APDs)短期作用对MK801诱导的精神分裂症模型小鼠体质量、摄食、糖脂代谢以及动物行为学的影响.将60只雄性昆明小鼠随机分成5组,分别给予连续7 d的生理盐水,MK801,MK801加氟哌啶醇(2.0 mg/kg)(HAL),MK801加利培酮(1.0 mg/kg)(RIS),MK801加阿立哌唑(4.0 mg/kg)(ARI)处理.结果显示,MK801诱导的精神分裂症模型组自发活动(旷场实验)较正常组显著增加.模型组小鼠体质量、摄食及糖脂代谢参数均无显著性变化.加入APDs处理后,与模型组比较,3种药物均能显著降低小鼠的自发活动,该参数与血脂中的甘油三酯(TG)和总胆固醇(TC)的浓度呈显著的负相关;此外,TG浓度还与肝脏组织中重要的转录因子SREBP1c的表达增加呈显著的正相关,与组蛋白受体H1R的表达增加也呈显著的正相关.其中,利培酮表现出较强的引发代谢紊乱的趋势,该药物促进了肝脏组织中SREBP1c和SREBP-2以及H1R的表达显著升高.因此得出,在APDs短期作用下,阿立哌唑无明显糖脂代谢紊乱,具有安全性高、不良反应小的特点.氟哌啶醇的过度镇静效应,可能是这类药物诱发一定程度的代谢性副反应的主要原因;而利培酮作为临床治疗重型精神疾病的一线用药,能较好地发挥疗效,但因其与其他靶点的亲和效应,可能引起更为严重的代谢紊乱副反应,并独立于体质量的增加.
关键词:  精神分裂症  抗精神病药物  不良反应  代谢紊乱
DOI:10.13718/j.cnki.xdzk.2019.12.006
分类号:R975;Q546
基金项目:重庆市留学人员回国创业创新支持计划项目(cx2018089);中央高校基本业务费项目(XDJK2018B037,SWU115071).
Effects of Short-Term Treatment of Haloperidol, Risperidone or Aripiprazole on Gluco-Lipid Metabolism and behaviors in Mice
ZENG Yan-ping, HU Zhong-yi, CHEN Xiao-ying, HU Chang-hua, LIU Xue-mei
School of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
Abstract:
To investigate whether different APDs affect body weight gain, food intake, gluco-lipid metabolism and behaviors after the short-term treatment of haloperidol, risperidone or aripiprazole in a schizophrenic animal model through administration of MK-801, sixty male Kunming mice were randomly divided into 5 groups and treated with vehicle (n=12/group), MK801, MK801 plus haloperidol (2.0 mg/kg), MK801 plus risperidone (1.0 mg/kg) or MK801 plus aripiprazole (4.0 mg/kg) for 7 days. MK801 treatment stimulated hyper-locomotor effects in the open field test. No conspicuous changes in body weight gain, food intake and other gluco-lipid metabolic parameters were observed in the MK801-only treatment group. After APD treatment, a reduction in locomotor behavior was found, which showed a significant negative relationship with plasma triglyceride (TG) and total cholesterol (TC) concentrations. Moreover, a significant positive correlation between plasma TG and hepatic SREBP1c levels as well as Histamine (1) receptor (H1R) levels was observed. Especially, short-term risperidone treatment significantly elevated dyslipidemia, which upregulated the levels of SREBP1c, SREBP-2 and H1R in the liver of mice. In conclusion, aripiprazole has fewer metabolic side effects; haloperidol may cause an over sedation effect, which is probably associated with some metabolic side effects; an increase in hepatic lipogenesis induced by risperidone may be one of the important factors of the metabolic side effects.
Key words:  schizophrenia  antipsychotic drug  side effect  metabolic dysfunction
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