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(eNOS)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eNOS、eNOS-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,eNOS总蛋白表达升高,eNOS-ser1179表达升高(P<0.05),eNOS 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 eNOS 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 eNOS mRNA was measured with RT-PCR, as the expression of eNOS and eNOS -ser1179 protein was detected by Western blot .The con-centrations 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 sig-nificantly higher expression in eNOS protein , eNOS mRNA and eNOS-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 .