改善氧化/抗氧化应激平衡及NET和5-HTT表达与瑞波西汀抗抑郁作用有关  

Improvement of oxidative/anti-oxidative stress balance and expressions of NET and 5-HTT involved in the anti-depressive effect of reboxetine

作　　者：李娜[1] 王涵[1] 文威[1] 周岐新[1] 

机构地区：[1]重庆医科大学药理学教研室,重庆400016

出　　处：《中国药理学通报》2011年第9期1295-1299,共5页Chinese Pharmacological Bulletin

摘　　要：目的探讨瑞波西汀抗慢性轻度不可预见性刺激(CUMS)致大鼠抑郁症行为与机体氧化/抗氧化应激平衡以及去甲肾上腺素转运体(NET)和5-羟色胺转运体(5-HTT)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)、瑞波西汀(0.7 mg.kg-1.d-1)灌胃的模型组(RMG)和正常对照组(RNG)。采用孤养结合CUMS方式建立大鼠抑郁模型。以开场实验与糖水消耗实验评价大鼠抑郁行为,生物化学方法检测大鼠血清丙二醛(MDA)含量及超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活力,RT-PCR法测定脑桥NET和海马5-HTT mRNA表达;光镜观察HE染色海马切片的病理形态改变。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含量升高,SOD和CAT活力及NET和5-HTT表达均下降,海马神经细胞出现明显核固缩和染色加深;给予瑞波西汀明显阻遏CUMS诱导的上述变化,但对正常组大鼠无影响。结论瑞波西汀可能通过逆转氧化/抗氧化应激系统失衡,增加NET和5-HTT的表达而产生抗抑郁作用。Aim To investigate the relationship between the anti-depressive effect of reboxetine and the oxidative/anti-oxidative stress balance as well as ex- pressions of NET and 5-HTT in rat depressive model induced by chronic unpredictable mild stress （CUMS）. Methods Sixty male SD rats were randomly divided into normal group（NG）, model group（MG）, reboxetine （0.7 mg · kg-1 · d-1 ）-treated normal group （RNG）, and reboxetine（0. 7 mg · kg· d-1）-treated model group（RMG）. CUMS with solitary condition was taken to establish rat depression model. The openfield test and sucrose consumption were used to evaluthe depression behaviors of rats. Biochemistry methods were used to determine the content of MDA and activities of SOD and CAT in serum. Reverse tran- scription polymerase chain reaction （RT-PCR） method was used to determine the mRNA expressions of NET and 5-HIT in either pons cerebelli or hippocampus tis-sues of rats. Hippocampal pathological change with HE staining slices was observed under microscope. Results It was shown that except MDA level, there were significant decreases of open-field scores （ crossing, rea- ring, and preening activities）, sucrose consumption, SOD and CAT activities, and expressions of NET and 5- HTY, as well as obvious karyopyknosis and deep stai- ning of hippocampal neurocytes in MG, in comparison with NG. The treatment of roboxetine obviously blunted the changes above caused by CUMS. However treatment of roboxetine had no influences on NG rats. Conclusions The treatment of reboxetine can improve depression behaviors of rats through reversing imbalance of oxidative/anti-oxidative stress systems and increas- ing expressions of NET and 5-HTr.

关 键 词：瑞波西汀 CUMS 抑郁症 氧化应激 NET 5-HTT 

分 类 号：R-332[医药卫生] R322.81