摘要
目的:研究帕罗西汀抗慢性轻度不可预见刺激(CUMS)致大鼠抑郁症作用与调节氧化应激平衡和下丘脑-垂体-肾上腺皮质(HPA)轴功能及脑源性神经营养因子(BDNF)表达的关系。方法:♂SD大鼠60只,随机分为正常对照组(NG)、模型组(MG)、帕罗西汀(1.8mg.kg-1.d-1)灌胃处理模型组及对照组。采用孤养结合CUMS方式建立大鼠抑郁症模型。以开场实验及糖水消耗试验评价大鼠抑郁行为,试剂盒测定血清丙二醛(MDA)含量及过氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性变化;放射免疫法分析血清皮质酮(CORT)浓度,RT-PCR法测定大鼠海马BDNF及下丘脑CRFmRNA表达。结果:与NG组相比,MG组大鼠在开场实验中水平得分、垂直得分和理毛次数以及糖水消耗均明显降低,血清MDA含量明显升高,SOD和CAT活性降低,血清COTR含量及下丘脑CRF表达明显升高,海马BDNF表达降低。给予帕罗西汀能够显著阻遏CUMS诱导的上述变化,但对正常组大鼠无明显影响。结论:帕罗西汀抗抑郁作用可能与减轻CUMS所致氧化应激损伤和改善HPA轴功能及阻遏神经细胞BDNF表达降低有关。
AIM： To investigate the correlation between antidepressive effect of paroxetine and improvements of oxidative stress,brain-derived neurotrophic factor（BDNF） expression and the hypothalamic-pituitary-adrenal（HPA） axis function in rat model induced by chronically unpredicted mild stress（CUMS）.METHODS： 60 male SD rats were randomly divided into following groups： normal group（NG）,model group（MG）,normal group-treated with 1.8 mg·kg-1·d-1 paroxetine（PNG）,and model group-treated with paroxetine（PMG）.Chronic mild unpredicted stress（CUMS） with solitary condition was taken to establish rat depression model.The open-field test and sucrose consumption were used to evaluate the behaviour changes of experimental rats.The malondialdehyde（MDA） levels,activities of superoxide dismutase（SOD） and catalase（CAT）,corticosterone（CORT） in serum,and expressions of BDNF in hippocampus and CRF in hypothalamus were determined by reagent kits,radio-immunoassay,and reverse transcription polymerase chain reaction（RT-PCR）,respectively.RESULTS：There were significant decreases of locomotor activities and sucrose water consumption,significantly increasing serum MDA and CORT levels with clearly decreasing SOD and CAT activities,and obviously decreasing expressions of BDNF and elevated CRF expression in model group,compared with NG.The treatment of paroxetine obviously improved the changes above induced by CUMS.However treatment of paroxetine had no significant influences on either behaviors or indices of NG rats.CONCLUSION： The antidepressive effect of paroxetine may involve in the improvements of oxidative stress/antoxidative stress balance,HPA axis function,and the expression of BDNF.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2012年第10期1137-1142,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
