经轻胶囊对大鼠抑郁的干预机制及性激素对大鼠脑干TPH₂基因表达的影响

【作者】 崔晓萍；

【导师】 张庆文；

【作者基本信息】 成都中医药大学 ， 中医妇科学， 2008， 博士

【摘要】 目的:分析性激素异常与精神情绪障碍之间的内在联系,用高剂量雌激素造成大鼠抑郁模型,探讨中药经轻胶囊的干预机制;分别用雌激素、孕激素、雄激素刺激雌鼠、雄鼠,进一步探索性激素对大鼠行为及脑干5-HT、TPH₂基因表达的影响,分析性激素与抑郁的相关性。方法:选择3—4月龄雌性和雄性SD大鼠,分别对每只雌鼠进行阴道脱落细胞涂片观察,逐只建立动情周期档案。在第一个实验中选择符合条件的大鼠,随机分为8组:雌鼠空白组、雄鼠空白组、雌鼠雌激素模型组、雄鼠雌激素模型组、利血平模型组、雌鼠雌激素模型+中药组、雄鼠雌激素模型+中药组、利血平模型组+中药组。选择大鼠的动情期,每日上午皮下注射苯甲酸雌二醇注射液,连续3天。造成实验大鼠体内高雌激素状态,按不同组别给予经轻胶囊干预,观察大鼠行为学、血清雌二醇、孕酮、睾酮、脑干神经递质5-HT的变化及TPH₂的基因表达。在第二个实验中,选择符合条件的大鼠随机分为6组:雌鼠空白组、雌鼠雌激素组、雌鼠孕激素组、雌鼠雄激素组、雄鼠空白组、雄鼠雌激素组。按不同组别分别于每日上午（雌鼠在动情期）给予高剂量的雌激素、孕激素、雄激素,连续3天,观察大鼠行为学、脑干神经递质5-HT及TPH₂基因表达的变化。结果:两个实验均表现出:高剂量雌激素可使大鼠反应性降低、迷宫总路程缩短,脑干5-羟色胺含量减少,Tph₂基因表达程度升高;实验大鼠表现出活动迟缓、反应淡漠、无抵抗、身体发软,说明在大鼠动情期给予外源性高剂量雌激素,可以造成实验大鼠出现抑郁状态。这种变化与利血平造模组变化趋同。经轻胶囊能改变动物的抑郁行为,增加大鼠迷宫总路程,降低E₂水平,增加脑干5-HT含量,降低Tph₂的基因表达。高剂量雄激素能升高大鼠行为总分,降低脑干5-HT灰度值,降低Tph₂基因表达程度;雌激素与雄激素对大鼠的影响有显著差异。结论:在大鼠动情期给予外源性高剂量雌二醇可造成大鼠抑郁状态,中药经轻胶囊可改善高剂量雌激素所造成抑郁状态大鼠的病理变化,纠正大鼠的抑郁行为。高剂量雌激素可降低脑干神经递质使大鼠出现抑郁,高剂量雄激素可增加脑干神经递质使大鼠出现兴奋。更多还原

【Abstract】 Objective:The objective of this dissertation is to analyze the relationship between sex hormones and depression,to investigate intervention mechanisms of Jingqing capsules through the rat models of premenstrual depression state caused by exogenous high-dose-estrogen,to Explore inflection of sex hormone for rats’ behaviors and 5-HT and gene expression of TPH₂ in brain stem,and analyze the relationship between menstrual depression and high-level-estrogen by injecting different sex hormones into different sex experimental rats.Methods:We used animal model of three to four months old impregnated SD female and male rats, performed vaginal smear test for each female rats and set up the files of estrous cycle individually.We Choose rats according with demands,randomly divided the rats into eight different experimental groups,female rats contrast group,male rats contrast group,female rats Estradiol group,male rats Estradiol group,the reserpine model group,female rats Estradiol with Jingqing Capsule group,male rats Estradiol with Jingqing Capsule group,the reserpine model with Jingqing Capsule group.We injected Estradiol Benzoate into experimental rats on three consecutive mornings to introduce high-level-estrogen state,made the model during the estrous period.At the same time of modeling, given Jingqing Capsule for different group and observed changes of rats’ behavioral,Estradiol, progestin,testosterone as well as changes of 5-HT and gene expression of TPH₂ in brain stem.Choose rats according with demands in the Second experiment,Randomly divided the rats into six different experimental groups:female rats contrast group,female rats Estradiol group,female rats progestagen group,female rats androgenic hormones group,.male rats contrast group,.male male Estradiol group. Given exogenous estrogen,progestagen and androgenic hormones on three consecutive mornings （during the estrous period of female）.Observed changes of rats’ behavioral changes as well as changes of 5-HT and gene expression of TPH₂ in brain stem.Results:high-dose-estrogen can decrease response degree to external stimulant,shorten rats’ covered distance of y + labyrinth test,decrease the 5-HT content in brain stem,increase gene expression of TPH₂.Experiments rats are slowmoving, response is indifferent,body is soft and no resistance.These results show that exogenous high-dose-estrogen can cause depression in experimental rats when given during the late estrous period.These were also found in reserpine model group.Qingjing capsules can reduce depression in the animal,increase rats’ covered distance of y + labyrinth test,decrease level of E₂.increase 5-HT content in the brain stem,decrease gene expression of TPH₂.High-dose-androgenic can increase rats’ behavior total grade,decrease 5-HTgrey-number in the brain stem,decrease gene expression of TPH₂.These deferens between estradiol and androgenic hormones are obvious.Conclusion: Exogenous high-dose-estradiol during the estrous period can cause the premenstrual depression state in experimental rats,Jingqing capsules can reduce the pathological change,and hence the animal’s depression can be relieved.Exogenous high-dose-estradiol can decrease experimental rats’ quantities of neurotransmitter in the brain stem,hence experimental rats show depression.High-dose-androgenic hormones can increase rats’ quantities of neurotransmitter in the brain stem,so experimental rats show excitation.更多还原