ISSN 0439-755X
CN 11-1911/B
主办：中国心理学会
　　　中国科学院心理研究所
出版：科学出版社

心理学报 ›› 2011, Vol. 43 ›› Issue (03): 283-293.

• • 上一篇    下一篇

胆囊收缩素对脂多糖诱发的病态行为及外周细胞因子的影响

邝雪莹;林文娟;王东林;亓晓丽;潘玉芹;孙菡;谢希   

  1. 中国科学院心理健康重点实验室, 中国科学院心理研究所, 北京100101
  • 收稿日期:2010-06-30 修回日期:1900-01-01 出版日期:2011-03-30 发布日期:2011-03-30
  • 通讯作者: 林文娟

The Effect of Cholecystokinin Octapeptide on Lipopolysaccharide-induced Sickness Behavior and Peripheral Cytokine Secretion

KUANG Xue-Ying;LIN Wen-Juan;WANG Dong-Lin;QI Xiao-Li;PAN Yu-Qin;SUN Han;XIE Xi   

  1. Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
  • Received:2010-06-30 Revised:1900-01-01 Published:2011-03-30 Online:2011-03-30
  • Contact: LIN Wen-Juan

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摘要： 细胞因子在病态行为的产生中有重要的作用。八肽胆囊收缩素在前人研究中表明能够拮抗脂多糖在大鼠体内引起的细胞因子的分泌。实验目的：利用八肽胆囊收缩素的抗炎作用研究细胞因子在病态行为中的作用。实验方法：共分两个实验进行, 将大鼠分为控制组、免疫激活剂脂多糖组(200 μg/kg剂量, 腹腔注射)以及注射不同剂量的八肽胆囊收缩素的实验组(分别为20 μg/kg 、40 μg/kg 、80 μg/kg 和120 μg/kg剂量), 各实验组在注射脂多糖前半小时注射相应剂量的八肽胆囊收缩素, 药物注射两小时后进行行为实验 (糖水摄取量测验、旷场测验和高架十字迷宫测验), 然后对大鼠前炎性细胞因子包括白细胞介素-1β(IL-1β)、白细胞介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α)及抗炎性细胞因子白细胞介素-10(IL-10)的血清浓度进行分析。实验结果：脂多糖诱发大鼠产生病态行为, 与控制组相比, 脂多糖组糖水摄取量降低, 旷场测验中活动性降低, 高架闭臂进入次数减少; 脂多糖诱导炎性细胞因子分泌增加, 与控制组相比, 脂多糖组前炎性细胞因子IL-1β、IL-6、TNF-α的分泌增加。在脂多糖注射前注射八肽胆囊收缩素能够抑制前炎性细胞因子IL-1β、IL-6、TNF-α的分泌, 但八肽胆囊收缩素未能改善免疫诱导的病态行为。结论：本实验结果表明仅改变外周的细胞因子浓度并不能完全改变动物的病态行为, 病态行为的产生可能与脑区的细胞因子有更大的联系。

关键词: 八肽胆囊收缩素, 脂多糖, 白细胞介素-1β, 白细胞介素-6, 白细胞介素-10, 肿瘤坏死因子-α, 病态行为

Abstract: Cytokines have been considered to be involved in the pathology of sickness behavior, but the role of peripheral cytokines in the pathology of sickness behavior is still elusive. Cholecystokinin octapeptide (CCK-8) has been proved to inhibit the lipopolysaccharide (LPS)-induced secretion of peripheral proinflammatory cytokines in rats. Aim: To investigate the role of peripheral cytokines in the pathology of sickness behavior. Methods: The experiment included two parts. In Experiment 1, forty-six rats were randomly divided into 4 groups: control, LPS, CCK-40+LPS and CCK-40, each group comprised twelve rats except ten rats for the control group, and in Experiment 2 forty-eight rats were randomly divided into six groups: control, LPS, CCK-20+LPS, CCK-40+LPS, CCK-80+LPS, CCK-120+LPS, each group comprised eight rats. The CCK groups were injected with different dosages of CCK-8 solution (20μg/kg, 40μg/kg, 80μg/kg and 120μg/kg doses respectively, i.p.) half an hour before the injection of LPS (200μg/kg, i.p.), and then 2 hours after the LPS injection, the sickness behavior was measured in behavioral experiments (including the sugar-water consumption test, open field test, and elevated plus maze test), and the cytokines in serum were analyzed by immunoassays. Results: LPS induced sickness behavior: LPS group consumed less sugar water and exhibited less activities in open field test and elevated plus maze test when compared with the controls; LPS also significantly increased cytokine production including IL-1β, IL-6 and TNF-α. However, the LPS-induced sickness behavior could not be attenuated by CCK-8, though CCK-8 significantly inhibited the LPS-induced proinflammatory cytokines of IL-1β, IL-6 and TNF-α compared to the LPS group. Conclusion: The inhibition of the secretion of peripheral proinflammatory cytokines can not antagonize the lipopolysaccharide-induced sickness behavior. The peripheral proinflammatory cytokines might be not directly responsible for the sickness behavior. The cytokines acting in brain may be more related to the sickness behavior, which needs further investigation.

Key words: Cholecystokinin octapeptide, Lipopolysaccharide, Interleukin-1β, Interleukin-6, Interleukin-10, Tmor necrosis factor-α, Sickness behavior