经轻胶囊抗经前高雌抑郁的初步药效研究

【作者】 肖新春；

【导师】 张庆文；

【作者基本信息】 成都中医药大学 ， 中医妇科学， 2006， 博士

【摘要】 研究目的：通过实验手段，初步探讨中药对高雌激素造成的经前抑郁状态的治疗效果及其对中枢神经递质5-HT的干预机制。 研究方法：首先选择35～45日龄KM小鼠，先设立空白组、雌激素组、雌激素+吗氯贝胺组、雌激素+左洛复组、雌激素+经轻胶囊低剂量组、雌激素+经轻胶囊高剂量组，逐只建立动情周期档案，在动情期给药，观察雌激素、雌激素+阳性对照药及雌激素+中药对小鼠体重、阴道角化细胞指数等一般情况及悬尾不动时间的影响。再设立生理盐水+5-HTP组、雌激素+5-HTP组、雌激素+吗氯贝胺+5-HTP组、雌激素+左洛复+5-HTP组、雌激素+低剂量经轻胶囊+5-HTP组、雌激素+高剂量经轻胶囊+5-HTP组，一般观察及给药时间与悬尾实验小鼠相同，主要观察雌激素、雌激素+阳性对照药、雌激素+中药对5-HTP诱导的小鼠甩头行为的影响。然后选择3～4月月龄SD大鼠，设立空白组、雌激素组、雌激素+吗氯贝胺组、雌激素+左洛复组、雌激素+经轻胶囊组，亦逐只建立动情周期档案，在动情期给药。观察皮下注射苯甲酸雌二醇对大鼠阴道角化细胞指数、血清E₂、P、脑干单胺类神经递质、大脑皮层MAO、海马5-HT_1A受体和5-HT_2A受体表达等的影响，探讨中药经轻胶囊对高雌激素导致的经前抑郁状态大鼠的中枢5-HT的可能影响机制。 实验结果：外源性的高雌激素可以造成实验鼠持续高阴道角化指数，增加悬尾实验小鼠的不动时间，减少5-HTP诱导的小鼠甩头次数，使实验大鼠脑干5-HT含量降低，大脑皮层MAO活性增强，海马5-HT_1A受体表达下降和5-HT_2A受体增强。中药经轻胶囊可对抗雌激素对小鼠悬尾实验、5-HTP增强实验的影响，可以降低实验鼠过高的阴道角化细胞指数，降低大鼠血清E₂、E₂／P、增加脑内5-HT含量，降低大脑皮层MAO活性，调节5-HT受体功能。 结论：在实验动物的动情期给予外源性高剂量雌二醇，可造成抑郁状态，并可使相关神经递质5-HT及其代谢酶、受体发生变化，与抑郁症的病理改变相近；经轻胶囊可以降低体内过高的雌激素水平，改善上述病理变化。更多还原

【Abstract】 Objective: Elementarily through the experimental method, discuss the treatment of Chinese herbs for the premenstrual depression state which is made by high estrogen level. Then explore and analyze the mechanism for the effect on 5-HT in the central nervous system which is taken by Chinese herbs.Methods: Firstly, KM mouse aged at 35-45 days were divided into six groups: （1） control group;（2） Estradiol group, （3）Estradiol with Moclobemide group; （4）Estradiol with Zoloft group; （5） Estradio with Jingqing Capsule with little dose group;（6） Estradiol with Jingqing Capsule with great dose group. Through setting the files of estrous cycle individually, injecting estradiol benzoate via subcutaneous injection except control group during the estrous period.At the same time, the rats of the Estradiol with Moclobemide group was given Moclobemide by gavage; Estradiol with Zoloft group, Zoloft; Estradio with Jingqing Capsule with little dose group, Jingqing Capsule with little dose; Estradiol with Jingqing Capsule with great dose group, Jingqing Capsule with great dose .We observed the index of vaginal keratinocyte, the duration of immobility in mouse tail suspension test,and so on. Secondly, 5-HTP induced head-twitches test was used . KMmouse aged at 35-45 days were divided into six groups: （1） physiological saline with 5-HTP group;（2） Estradiol with 5-HTP group, （3）Estradiol and Moclobemide with 5-HTP group; （4）Estradiol and Zoloft with 5-HTP group; （5） Estradiol and Jingqing Capsule with little dose with 5-HTP group;（6） Estradiol and Jingqing Capsule with great dose with 5-HTP group. After administration 5-HTP, head-twitch response was observed. Thirdly, rats aged at 3-4months were divided into five groups: （1） control group;（2） Estradiol group, （3）EstradioI with Moclobemide group; （4）Estradiol with Zoloft group; （5） Estradiol with Jingqing Capsule with great dose group.Serum E₂,P were更多还原