【作者】 耿甄彦；

【导师】 徐维平； 魏伟；

【作者基本信息】 安徽医科大学 ， 药理学， 2009， 硕士

【摘要】 目的:通过建立急性应激、药物诱导和慢性应激小鼠抑郁模型,观察黄精皂苷(Saponins of Rhizoma Polygonati, SRP)对各种抑郁模型小鼠行为的影响,以及SRP对慢性应激抑郁模型小鼠脑内去甲肾上腺素(norepinephrine, NE)、多巴胺(dopamine, DA)、5-羟色胺(5-hydroxytryptamine, 5-HT)三种单胺类神经递质和血中皮质醇(cortisol, COR)的影响,初步探讨SRP对抑郁模型小鼠的影响及其作用机制。方法:1、采用不同的方法建立不同的小鼠抑郁模型:⑴采用小鼠悬尾和小鼠强迫游泳建立急性应激致小鼠行为绝望模型,观察SRP对小鼠悬尾不动时间和强迫游泳不动时间的影响。⑵通过利血平建立药物诱发的抑郁小鼠模型,观察SRP对利血平诱发小鼠体温下降、眼睑下垂和活动抑制的影响。⑶利用孤养和长期不可预见性温和应激(chronic unpredictable mild stress, CUMS)建立慢性应激小鼠抑郁模型,观察小鼠体重的变化,采用敞箱实验测定小鼠探求活动的变化,利用自主活动仪测定小鼠自主活动的变化,通过水迷宫测定小鼠学习记忆能力的变化。2、采用高效液相色谱法(high performance liquid chromatography, HPLC)测定慢性应激抑郁模型小鼠脑内单胺类神经递质的变化,用放免法(radioimmunityassay, RIA)测定血中COR的变化。结果:1、⑴与正常组小鼠相比较,SRP(100、200、400 mg·kg-1)均可显著减少小鼠悬尾不动时间和小鼠强迫游泳不动时间。⑵与模型组小鼠相比较,SRP(100、200、400 mg·kg-1)均可显著对抗利血平所引起的体温下降、眼睑下垂及活动抑制。⑶与正常组相比,模型组小鼠的体重增长值、敞箱活动及自主活动明显减少;与模型组相比,SRP(100、200、400 mg·kg-1)组小鼠的体重增长值、敞箱活动及自主活动均有增加。在水迷宫定位航行实验中,从第2天开始模型组与正常组相比,小鼠的逃避潜伏期明显延长,与模型组相比,SRP(100、200、400 mg·kg-1)小鼠的逃避潜伏期均明显缩短;撤去平台后,与正常组相比,模型组小鼠在原平台象限的搜索时间明显缩短,与模型组相比,SRP(100、200、400 mg·kg-1)组小鼠在原平台象限的搜索时间明显延长。2、经过21天刺激后,与正常组相比,慢性应激模型组小鼠脑内的NE、DA和5-HT的含量均明显降低,血中COR含量明显升高;与模型组相比,SRP(100、200、400 mg·kg-1)组小鼠脑内的NE和5-HT的含量明显升高,DA的含量有升高趋势,但差异无显著性,血中COR含量降低。结论:SRP能够改善抑郁模型小鼠的行为学,并且能够提高慢性应激抑郁模型小鼠脑内单胺类神经递质(NE, DA,和5-HT)的含量,降低血中COR的含量,SRP对小鼠脑内神经递质和血中COR的作用可能是SRP对抑郁模型小鼠产生影响的可能机制。更多还原

【Abstract】 Objective : After establishing the acute stress, drug-induced and chronic stress mouse models of depression,we observed the effects of Saponins of Rhizoma Polygonati(SRP), on behaviors of all the models. And studied on the effects of the SRP on norepinephrine(NE), dopamine (DA), 5-hydroxytryptamine(5-HT), and cortisol(COR) in mouse model of depression with chronic stress. Then discussed the prevention and cue effects of the SRP and the possible mechanisms.Methods: 1. Established different depression models of mouse in different ways :⑴In this study, we adopt the tail suspention and force swimming of the mouse of two" the behavior despair" to observe effect of the SRP on suspention and force swimming immobility time of the mouse.⑵In this study, we set up the drug-induced depression model by reserpine, and then observed the ptosis, akinesia and hypothermia which induced by reserpine.⑶The depression model of mouse was made by the CUMS and solitary custody. We observed the change of the weight of the mouse, and completed the detection of autonomous activity, open-filed test, and water maze test.2. Using the High Performance Liquid Chromatography(HPLC) detected the monoamine neurotransmitters of the CUMS depression model; and deteced the COR with the radioimmunity assay (RIA).Results: 1、⑴The SRP(100、200、400 mg·kg-1) significantly diminished the immobility time of the mice in the suspention and force swimming.⑵After administration of the SRP for 7 days, it can notably alleviate the symptoms of the ptosis, akinesia and hypothermia which occurred in the vehicle group.⑶The SRP(100、200、400 mg·kg-1) all increased the weight of the mice; The numbers of crossings and rearings in the open field test and the autonomous activity were increased as well. According to our findings of water maze , the SRP(100、200、400 mg·kg-1) shortened the Escape latent period from the second day obviously, and prolonged the cross the Platform Quadrant times.2、The SRP(100、200、400 mg·kg-1) significantly increased the NE and 5-HT in the brian of the CUMS depression model mouse; the contents of the DA had rising trend; and the COR in the serum decreased.Conclutions: The SRP can improve the diversify of the behaviors, elevate the contents of the NE, DA and 5-HT in the brian and the COR in the serum which are the possible mechanisms of the prevention and cure effect of the SRP.更多还原