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作 者:费慧芝[1] 胡小娅[2] 邱红梅[2] 刘丹[3] 周岐新[2]
机构地区:[1]重庆三峡医药高等专科学校药理学教研室,万州404100 [2]重庆医科大学重庆生物化学和分子药理学重点实验室,重庆400016 [3]重庆市中山医院,重庆400016
出 处:《中国药科大学学报》2016年第4期474-478,共5页Journal of China Pharmaceutical University
基 金:国家自然科学基金资助项目(No.31400881)~~
摘 要:采用孤养结合慢性不可预见性温和刺激(CUMS)方式建立抑郁模型,探讨丙戊酸钠抗抑郁作用与改善海马去甲肾上腺素转运体(norepinephrine transporter,NET)、5-羟色胺转运体(serotonin transporter,5-HTT)表达之间的关系。60只雄性SD大鼠随机分为对照组(NG)、模型组(MG)、丙戊酸钠对照组(VNG)及丙戊酸钠模型组(VMG)。通过开场实验、强迫游泳试验评价大鼠抑郁行为。通过生物化学法测定血清丙二醛(MDA)含量及超氧化物酶(SOD)、过氧化氢酶(CAT)活性;以实时定量RT-PCR法及Western blot分析丙戊酸钠对大鼠海马NET、5-HTT mRNA及蛋白表达的影响。实验结果表明:CUMS致模型组大鼠活动减少,不动时间明显增加,MDA含量升高,SOD、CAT活性下降,海马NET mRNA及蛋白表达显著升高,5-HTT mRNA及蛋白表达明显降低,而丙戊酸钠干预可明显阻遏以上变化,但对对照组大鼠无显著影响。以上结果提示,丙戊酸钠抗抑郁作用可能涉及改善CUMS大鼠海马NET及5-HTT mRNA及蛋白的表达。This study aimed at investigating the correlations between antidepressive effect of valproate and improvements of NET and 5-HTT expression in depressive rats leaded by chronic mild unpredicted stress (CUMS) with solitary condition. Sixty male SD rats were divided into normal group (NG), model group (MG), valproate treated-normal group (VNG), and valproate treated-model group (VMG), randomly. The changes of depressive behaviors were evaluated by the open-field test and force swimming test. The contents of MDA, activi- ties of SOD and CAT in serum, the mRNA and protein expression of NET, 5-HTT in hippocampus were deter- mined by biochemical methods, Real-time PCR and Western Blot, respectively. Results showed that CUMS can significantly decrease the activities in open-field test, SOD and CAT activities in serum, expression of 5-HTT in hippocampus, and obviously increase the immobility time in force swimming test, the level of MDA and expression of NET. The treatment of valproate obviously improved the changes induced by CUMS. However, the treatment of valproate had no significant influences on behaviors of NG rats. So, it revealed that improvements of the mRNA and protein expression of NET, 5-H3"F may be involved in the antidepressive effect of valproate.
关 键 词:慢性不可预见性温和刺激(CUMS) 抗抑郁 丙戊酸钠 去甲肾上腺素转运体 5-羟色胺转运体
分 类 号:R749.4[医药卫生—神经病学与精神病学]
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