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考察角鲨烯对慢性轻度不可预见刺激模型小鼠行为学及其谷氨酸毒性通路相关蛋白的影响。采用13种不同刺激[食物剥夺、噪音、闪光、热刺激(45℃)、制动、冷冻(4℃)、摇晃、湿笼、夹尾、饮水剥夺、游泳、电击和异物]对雄性BALB/C小鼠连续刺激35天建立慢性轻度不可预见应激模型。从第3周开始连续灌胃给予3个剂量的角鲨烯(80、40和20 mg·k~(g-1)·d~(-1))3周后,测定各组小鼠行为学变化,采用反相HPLC法测定海马谷氨酸(glutamate,GLU)含量,分光光度法测定超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathioneperoxidase,GSH-Px)活力和丙二醛(malondialdehyde,MDA)含量,取海马组织进行蛋白免疫印迹方法测定N-甲基-D-天冬氨酸受体亚基ε-2(N-methyl-D-aspartate receptor subunits epsilon-2,NMDAε2)、钙调蛋白激酶Ⅱ(calmodulin kinaseⅡ,Ca MKⅡ)和神经性一氧化氮合酶(neuronal nitric oxide synthase,NOS1)蛋白的表达。与模型组比较,角鲨烯能增加抑郁模型小鼠的体重、糖水偏好率和水平运动和垂直运动次数(P<0.05),缩短悬尾实验和强迫游泳实验的不动时间(P<0.05),降低海马GLU和MDA含量(P<0.05),升高SOD、GSH-Px活力(P<0.05),下调海马NMDAε2、Ca MKⅡ和NOS1蛋白的表达(P>0.05)。综上所述,角鲨烯对抑郁模型小鼠表现出明显的抗抑郁作用,在此过程中引起的氧化应激降低和GLU-NMDAε2-Ca MKⅡ-NOS1通路相关蛋白下调可能与其抗抑郁作用有关。
To investigate the effects of squalene on behavior and glutamate toxic pathway-associated proteins in chronic mild unpredictable stimulus model mice. Male BALB / c mice were challenged with 13 different stimuli (food deprivation, noise, flash, thermal stimulation (45 ° C), brakes, freezing at 4 ° C, shaking, wet cages, pinch, water deprivation, swimming, C mice were stimulated continuously for 35 days to establish chronic mild unpredictable stress model. Three doses of squalene (80, 40 and 20 mg · kg -1 · d -1) were administered orally for 3 weeks after the third week, and then the behavior of the mice in each group was determined The levels of glutamate (GLU) in hippocampus were determined by reverse phase HPLC. The levels of superoxide dismutase (SOD) and glutathioneperoxidase (GSH-Px) were measured by spectrophotometry. The content of malondialdehyde (MDA) in hippocampus of hippocampus was determined by Western blotting. The N-methyl-D-aspartate receptor subunits epsilon -2, NMDAε2), and expression of calmodulin kinase Ⅱ (Ca MKⅡ) and neuronal nitric oxide synthase (NOS1). Compared with the model group, squalene increased the body weight, preference of sugar and water and the number of horizontal and vertical movements (P <0.05) in depression model mice, shortened the immobility time of tail suspension test and forced swimming test (P <0.05) (P <0.05), increased the activities of SOD and GSH-Px (P <0.05), and decreased the expressions of NMDAε2, Ca MKⅡ and NOS1 in the hippocampus (P> 0.05). In summary, squalene exerts a significant antidepressant effect on depression model mice, and the decreased oxidative stress and down-regulation of GLU-NMDAε2-Ca MKⅡ-NOS1 pathway-related proteins may be related to their antidepressant effects .