PSYCH OpenIR  > 健康与遗传心理学研究室
外周细胞因子在大鼠病态行为中的作用
邝雪莹
学位类型硕士
导师林文娟
2010-07
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业心理学
关键词病态行为 细胞因子 脂多糖 八肽胆囊收缩素 氟西汀
摘要机体接受免疫应激后细胞因子分泌增加,细胞因子对机体的作用会诱导病态行为的出现,但细胞因子在病态行为病理机制中的具体作用尚未研究清楚。本学位论文以探讨外周细胞因子浓度变化与病态行为之间的关系为研究目的,以脂多糖诱发大鼠病态行为作为病态行为模型,在脂多糖注射前对大鼠注射具有抗炎性的八肽胆囊收缩素和临床上广泛应用的抗抑郁药物氟西汀来抑制脂多糖诱发的细胞因子分泌,然后考察动物病态行为表现与动物外周前炎性细胞因子(IL-1β、IL-6和TNF-α)和抗炎性细胞因子IL-10的浓度变化。本论文包括三组实验,分别是1)八肽胆囊收缩素对脂多糖诱发的病态行为与外周细胞因子分泌的影响,2)八肽胆囊收缩素影响脂多糖诱发的病态行为与外周细胞因子分泌的剂量效应,3)氟西汀长期与单次注射对脂多糖诱发的病态行为与外周细胞因子分泌的影响。实验方法是观察大鼠接受外周长期或单次药物注射后在糖水摄取量测定实验、旷场实验和高架十字迷宫实验等行为实验中的表现,以及测定大鼠的细胞因子血清浓度。实验结果显示,脂多糖(腹腔注射,剂量为200 μg/kg,下同)的急性注射诱发大鼠的病态行为出现和引起大鼠的外周细胞因子水平上升;在脂多糖注射前半小时注射八肽胆囊收缩素(腹腔注射,剂量分别为20 μg/kg、40 μg/kg、80 μg/kg和120 μg/kg)能有效抑制由于脂多糖引起的外周细胞因子的分泌,但抑制作用对IL-1β和TNF-α这两种细胞因子无明显的剂量效应;八肽胆囊收缩素并不能缓解脂多糖诱发的病态行为;氟西汀的长期(每天以20 mg/kg剂量腹腔注射,持续15天)与单次注射(脂多糖注射前半小时以20 mg/kg剂量腹腔注射氟西汀)均未能缓解脂多糖诱发的病态行为,氟西汀的单次注射对脂多糖诱发的前炎性细胞因子分泌有一定的抑制作用,氟西汀的单次注射能增加抗炎性细胞因子IL-10分泌;氟西汀的长期注射对脂多糖诱发的外周细胞因子TNF-α分泌有一定的抑制作用。本研究实验结果提示,外周前炎性细胞因子的分泌增加诱发病态行为,但拮抗外周前炎性细胞因子的分泌并不能有效缓解病态行为。
其他摘要The cytokines are synthesized and released in response to infection and inflammation, which could induce sickness behaviours in human beings as well as animals; however, the role of cytokines in the pathology of sickness behaviours is still not clear. The object of the thesis is to investigate the effects of the peripheral cytokines on sickness behaviours. The methods: The sickness behaviours were induced by lipopolysaccharide, a cytokine inducer, in rats. Before the injection of lipopolysaccharide, animals were pretreated with cholecystokinin octapeptide, an anti-inflammatory, or fluoxetine, one kind of antidepressants, to inhibit the release of proinflammatory cytokines. Following the injection, the effects of peripheral cytokines on the sickness behaviours and the change of the peripheral proinflammatory cytokines IL-1β, IL-6 and TNF-α and anti-inflammatory cytokine IL-10 were observed. This thesis included three experiments: 1) the effects of cholecystokinin octapeptide on the lipopolysaccharide-induced sickness behaviours and peripheral cytokines, 2) the effects of different doses of cholecystokinin octapeptide on the lipopolysaccharide-induced behaviours and peripheral cytokines, and 3) the effects of chronic and acute fluoxetine treatment on the lipopolysaccharide-induced behaviours and peripheral cytokines. Sickness behaviours were measured by using the sugar water consumption test, open field test and elevated plus maze after the injection, and cytokines in sera were analysed by immunoassays. The results: Lipopolysaccharide induced sickness behaviours and the release of cytokines including IL-1β, IL-6 and TNF-α in rats. The treatment of cholecystokinin octapeptide (20 μg/kg, 40 μg/kg, 80 μg/kg and 120 μg/kg, i.p., half hour before the injection of lipopolysaccharide) could abolish the lipopolysaccharide-induced release of cytokines (IL-1β、IL-6 and TNF-α), but this effect did not enhance when the dosage increased. Cholecystokinin octapeptide could not attenuate the lipopolysaccharide-induced sickness behaviours in all dosage. Both the chronic (15 days) and acute (half hour before the injection of lipopolysaccharide) fluoxetine (20 mg/kg, i.p.) treatment could not attenuate the lipopolysaccharide-induced sickness behaviours, though the acute fluoxetine treatment inhibited the lipopolysaccharide-induced cytokines (IL-1β、IL-6 and TNF-α), and the chronic fluoxetine treatment significantly inhibited TNF-α. It was also found that acute fluoxetine treatment per se increased peripheral IL-10 secretion while all other treatments have no effects on IL-10 secretion. These results suggested that the release of peripheral proinflammatory cytokines were involed in the development of sickness behaviours, but the inhibition of peripheral proinflammatory cytokines could not antagonize the sickness behaviours. 
学科领域医学心理学
语种中文
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/20286
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
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邝雪莹. 外周细胞因子在大鼠病态行为中的作用[D]. 北京. 中国科学院研究生院,2010.
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