上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

青春期亚慢性地卓西平暴露对小鼠成年期前脉冲抑制和糖耐量的影响

丁文华1，Dake Qi2，鞠培俊1，崔东红1   

  1. 1.上海交通大学 医学院附属精神卫生中心 上海市重性精神病重点实验室， 上海 200030； 2.美国耶鲁大学医学院内科， 纽黑文 06510
  • 出版日期:2014-06-28 发布日期:2014-06-30
  • 通讯作者: 崔东红, 电子信箱: donghong.cui@gmail.com。
  • 作者简介:丁文华（1985—）， 男， 硕士生; 电子信箱: dingwenhua1234@163.com。
  • 基金资助:

    国家自然科学基金面上项目（81171266, 81271481）

Effects of subchronic injection of dizocilpine during adolescence on prepulse inhibition and glucose tolerance of mice in adulthood

DING Wen-hua1, Dake Qi2, JU Pei-jun1, CUI Dong-hong1   

  1. 1.Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; 2.Department of Internal Medicine, Yale University School of Medicine, New Haven 06510, USA
  • Online:2014-06-28 Published:2014-06-30
  • Supported by:

    National Natural Foundation of China, 81171266, 81271481

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摘要：

目的 探讨青春期亚慢性地卓西平(MK-801)注射对小鼠成年期前脉冲抑制（PPI）和糖耐量的影响。方法 20只青春期小鼠随机分为对照组（n=10）和模型组（n=10），两组小鼠出生后30～43 d分别接受0.9%生理盐水（4 mL/kg）和MK-801（0.6 mg/kg）注射，1次/d，持续2周。每周记录摄食和体质量，并于小鼠成年期（出生后70～80 d之间）进行旷场试验、PPI测试和葡萄糖耐量试验（GTT）。结果 模型组小鼠在79 dB强度的前脉冲刺激时，PPI显著低于对照组（P<0.05），表明MK-801成功诱导小鼠精神分裂样行为。模型组小鼠体质量也显著低于对照组（P<0.05）。GTT结果显示：模型组小鼠注射葡萄糖后90 min和120 min的血糖水平显著高于对照组（P<0.001和P<0.01），表明MK-801诱导的精神分裂样小鼠模型出现糖耐量异常。两组小鼠的摄食量和旷场试验中的自发活动量差异均无统计学意义（P>0.05）。结论 青春期亚慢性注射MK-801可诱导小鼠成年期PPI损害和糖耐量异常。

关键词: 地卓西平, 精神分裂症, 前脉冲抑制, 糖耐量

Abstract:

Objective To investigate the effects of the subchronic injection of dizocilpine (MK-801) during adolescence on prepulse inhibition (PPI) and glucose tolerance of mice in adulthood. Methods Twenty mice in adolescence were randomly divided into the control group (n=10) and model group (n=10). After birth for 30-43 d, mice of two groups were injected with saline of 0.9% (4 mL/kg) and MK-801 (0.6 mg/kg) respectively once a day for two weeks. Food intake and body weight were measured each week. Open field test, PPI test, and glucose tolerance test (GTT) were performed in adulthood of mice (70-80 d after birth). Results The PPI of mice of the model group at prepulse of 79 dB intensity was significantly lower than that of the control group (P<0.05), suggesting that MK-801 successfully induced schizophrenia-like behavior of mice. Body weights of mice of the model group were significantly lower than those of the control group (P<0.05). Results of GTT showed that plasma glucose levels of mice of the model group were significantly higher than those of the control group at 90 min and 120 min after glucose injections (P<0.001，P<0.01), suggesting that abnormal glucose tolerance appeared in MK-801 induced schizophrenia-like mice. The differences of food intake and locomotor activities in open field tests of mice of the model group and control group were not statistically significant (P>0.05). Conclusion The subchronic injection of MK-801 during adolescence can induce the impairment of PPI and abnormal glucose tolerance of mice in adulthood.

Key words: dizocilpine, schizophrenia, prepulse inhibition, glucose tolerance