美托洛尔对抑郁症大鼠额叶皮质氧化应激的影响  

Effects and mechanism of metoprolol on the cortex oxidative stress in prefrontal lobe in rats with depression rats

作　　者：万砚 王艺明[1] 

机构地区：[1]贵州医科大学附属医院心理科,贵州贵阳550004

出　　处：《广东医学》2017年第3期340-344,共5页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(编号:81560235);国家科技支撑计划项目(编号:2015BAI13B02);贵州省科技计划项目(编号:黔科合平台人才[2016]5679)

摘　　要：目的观察一氧化氮(NO)、丙二醛(MDA)、超氧化物歧化酶(SOD)以及内皮型一氧化氮合酶(e NOS)在抑郁症大鼠额叶皮质表达的改变,探讨美托洛尔对抑郁症大鼠的影响及其机制。方法 40只雄性SD大鼠按随机数字法分为对照组、模型组、药物+模型组以及药物+对照组。给予模型组和药物+模型组21 d慢性刺激之后,药物+模型组和药物+对照组给予美托洛尔灌胃给药,模型组和对照组予生理盐水灌胃,对所有大鼠称重、进行行为学检测。酶标仪检测NO、SOD、MDA含量,使用Western blot和RT-PCR检测大鼠脑组织中e NOS、e NOS-ser1179相对表达量。结果美托洛尔改善大鼠抑郁样症状,与模型组比较,药物+模型组NO含量降低,SOD升高,MDA降低,e NOS总蛋白表达升高,e NOS-ser1179表达升高(P<0.05),e NOS mRNA表达升高。结论美托洛尔对改善大鼠抑郁症状有积极作用,可能与其减少抑郁症大鼠脑受到的氧化应激损伤有关。Objective To observe the concentrations of NO,MAD and SOD,and the expression of e NOS in the prefrontal cortex of rats with chronic unpredictable mild stress,thus to detect the effect and mechanism of anti- depression effect of metoprolol. Methods Forty SD rats were randomly divided into 4 groups,control group,model group,model plus metoprolol group,and control plus metoprolol group. The rats were exposed to the chronic unpredictable mild stress（ CUMS） and isolation to create a depression model. Open field test and sucrose water consumption test were performed to observe the behavior of animals after intragstric administration with metoprolol（ in control plus metoprolol and model plus metoprolol groups） or distilled water（ in control and model groups） for 22 days. The expression of e NOS mRNA was measured with RT- PCR,as the expression of e NOS and e NOS- ser1179 protein was detected by Western blot. The concentrations of NO,SOD and MDA were assessed by ELISA. Results Compared with the model group,the model plus metoprolol group were significantly lower in the concentrations of NO（ 6. 12 ± 1. 05 μmol/mg） and MDA（ 8.21±1. 25μmol/mg）;and higher in concentration of SOD（ 55. 59 ± 11. 07 U /mg）. Compared with the model group,there was significantly higher expression in e NOS protein,e NOS mRNA and e NOS- ser1179 protein in model plus metoprolol（ P〈0. 05）. Conclusion The metoprolol have positive effects in depression rats,which could be related with the decrease of the oxidative stress in the brain.

关 键 词：抑郁症 美托洛尔 过氧化物歧化酶 一氧化氮 

分 类 号：R114[医药卫生—卫生毒理学]