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抗炎性细胞因子IL-10 与IL-4 对大鼠抑郁行为的作用
其他题名Effects of anti-inflammatory cytokines IL-10 and IL-4 on depressive behavior in rats
徐说
2014-05
摘要研究背景:抑郁症的细胞因子假说为研究抑郁症的发病机理和临床治疗提供了新方向,因而备受研究者的关注。前炎性细胞因子参与抑郁症的发病,而抗炎性细胞因子则关系到抑郁症的治愈。然而,在实验室研究抗炎性细胞因子的抗抑郁作用时,所用动物模型的抑郁行为只能持续数个小时,难以与病态行为相区分。而且,仍不清楚抗炎性细胞因子的抗抑郁作用是否受到干预时间的影响。
研究目的:本研究的目的是观察抗炎性细胞因子白介素-10(Interleukin-10,IL-10)与白介素-4(Interleukin-4,IL-4)能否逆转持续数小时至24 小时的动物抑郁行为,并观察IL-10 的抗抑郁作用是否受到干预时间的影响。
研究方法:本研究采用中枢三次注射细菌脂多糖(Lipopolysaccharide,LPS)的大鼠抑郁模型,该模型的抑郁行为可从数小时持续到24 小时。首先以IL-10 和IL-4 为干预药物,在每次注射LPS 前2 小时干预,观察其对大鼠的体重变化、糖精水偏好、旷场测试运动距离和直立次数的影响。然后比较在注射LPS 前12小时与前2 小时使用IL-10 干预,对大鼠的体重变化、糖精水偏好、旷场测试活动距离和直立次数、及悬尾测试不动时间的影响。
结果:IL-10 能够改善部分大鼠中枢三次注射LPS 所致的快感缺乏和活动水平降
低的症状。IL-4 对大鼠中枢三次注射LPS 所致的快感缺乏无影响,但能够改善部分大鼠活动水平降低的症状。在注射LPS 前12 小时用IL-10 干预,比起提前2 小时用IL-10 干预,对部分大鼠抑郁行为的改善效果更优。
结论:本研究验证了抗炎性细胞因子IL-10 的抗抑郁作用,但并不是对全部动物都有效。IL-10 的抗抑郁效果与给药时间有关。
其他摘要Background: The cytokine hypothesis of depression has received considerable research attention for the mechanism study and the therapeutic treatments of depressive disorders. While pro-inflammatory cytokines have been demonstrated to play an important role in the pathological mechanism of depression , the anti- inflammatory cytokines are suggested to have some effects on alleviating depression-related symptoms. However, the animal models used for examination of the effects of anti- inflammatory cytokines on behavioral depression often last only a few hours, which can hardly be regarded as a model of depression. Moreover, whether the anti-depressant effects of anti- inflammatory cytokine are affected by the time of
administration is still unclear.
Objective: The purpose of this study was to investigate whether anti- inflammatory cytokines interleukin-10 (IL-10) and interleukin-4 (IL-4) can reverse the depressive behaviors which up to 24 hours, and whether the reversal effects of anti- inflammatory cytokines were affected by the administration time.
Methods: In this study, a rat model of depression induced by repeated central lipopolysaccharide(LPS) administration was used, which can induce significant depressive-like behaviors after 24 hours of the last LPS injection. Firstly, IL-10 or IL-4 was injected ICV 2 hours before LPS administration and its effects on the LPS-induced changes in body weight, saccharin preference, and open- field test was observed. Then IL-10 was injected ICV 12 hours of 2 hours before LPS was administered, and the changes in body, saccharin preference, open field test, and tail suspension test was measured.
Results: LPS-induced anhedonia and decreased motor activities can be reversed by IL-10 in some rats. IL-4 has no effect on anhedonia induced by LPS, yet it can improve motor activities in some rats. And ICV injection of IL-10 12 hours before LPS showed better anti-depressive effects than 2 hours.
Conclusions: This study indicated anti- inflammatory cytokine IL-10 has some antidepressant effect, though not in all the rats. It also suggests that IL-10's pharmacological efficacy may depend on its intervention time.
学科领域医学心理学
关键词抗炎性细胞因子 白介素-10 白介素-4 抑郁症 抑郁行为
学位类型硕士
语种中文
学位专业心理学
学位授予单位中国科学院研究生院
学位授予地点北京
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/19734
专题健康与遗传心理学研究室
作者单位中国科学院心理研究所
推荐引用方式
GB/T 7714
徐说. 抗炎性细胞因子IL-10 与IL-4 对大鼠抑郁行为的作用[D]. 北京. 中国科学院研究生院,2014.
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