经轻胶囊抗经前高雌抑郁的初步药效研究
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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E_2、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E_2、E_2/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。
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 . KM
    mouse 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 E_2,P were
引文
[1] 朱紫青,季建林,肖世富.抑郁障碍诊疗关键[M].南京:江苏科学技术出版社,2003,10:185.
    [2] HalbreichU, PettyF, Yonkers Ketal. Low plasmaγ-Aminobutyric acid levels during the late luteal phase of women with premenstrual dysphodc disorder[J]. Am J Psychiatry, 1996, 153: 718-720.
    [3] 龚绍麟.抑郁症[M].北京:人民卫生出版社,2003,2:8.
    [4] 蔡焯基,汤宜朗,马辛.抑郁症基础与临床[M].北京:科学出版社,2001,5:329.
    [5] 司徒仪.中西医结合妇产科学[M].北京:科学出版社,2003,8:181.
    [6] 王晓慧,孙家华.现代精神医学[M].北京:人民军医出版社,2002,9:1042.
    [7] 于传鑫,李诵絃.实用妇科内分泌学[M].上海:复旦大学出版社,2004,5:237-238.
    [8] 李继俊主译.临床妇科内分学与不孕[M].济南:山东科学技术出版社,2003,6:418.
    [9] 丰有吉,沈铿.妇产科学[M].北京:人民卫生出版社,2005,8:236.
    [10] 刘赛欧.妇产科综合征诊断治疗学[M].北京:人民军医出版社,2005,1:74.
    [11] 蒋先胜.雌激素与情感障碍[J].国外医学精神病学分册,2000,27(2):119.
    [12] 李焕德,彭文兴.抑郁症药物治疗新进展[J].国外医学精神病学分册,1997,24(3):129-133.
    [13] 王德智,罗焕頫,张丹.中国妇产科专家经验文集②[M].沈阳:辽宁科学技术出版社,2001,9:1150-1154.
    [14] 张玉珍主编.中医妇科学[M].北京:中国中医药出版社,2002,9:166.
    [15] 王小云,沈碧琼,张春玲.中医综合疗法治疗女性抑郁症60例[J].广东医学,2001,22(6):539.
    [16] 徐淑云,卞如濂,陈修.药理实验方法学[M].北京:人民卫生出版社,2002,1:807.
    [17] 施新猷.现代医学实验动物学[M].人民军医出版社,北京:2000,9:330-331.
    [18] 苗明三.实验动物与动物实验技术[M].北京:中国中医药出版社,1997,6:145.
    [19] 徐淑云,卞如濂,陈如修.药理实验方法学[M].北京:人民卫生出版社,2002,1:807.
    [20] Steru L, Chermat R, Thierry B, Simon P. Tail suspension test: A new method for screening antidepressants in mice. Psychopharmacology (Berl), 1985, 85(3): 367-370.
    [21] 蔡兵,崔承彬,陈玉华,等.巴戟天中菊淀粉型低聚糖类单体成分对小鼠的抗抑郁作用[J].中国药理学与毒理学杂志,1996,10(2):109.
    [22] 德:H.G.沃格尔,美:W.H.沃格尔编著.杜冠华,李学军,张永祥,等译.药理学实验指南[M].北京:科学出版社,2001,2:411.
    [23] Goodwin GM, Green AR, Johnson P. 5-HT_2 receptor characteristics in frontal cortex and 5-HT_2 receptor-mediated head-twitch behaviour following antidepressant treatment to mice. Br J Pharmacol, 1984, 83(1): 235-242.
    [24] 张均田主编.现代药理实验方法学(上册)[M].北京:北京医科大学中国协和医科大学联合出版社,1998,10:1063.
    [25] 陈勤主编.抗衰老研究实验方法[M].北京:中国医药科技出版社,1996,2,135-138.
    [26] 蔡焯基,汤宜朗,马辛.抑郁症基础与临床[M].北京:科学出版社,2001,5:323.
    [27] Yonkers KA. Special issues related to the treatment of depression in women [J]. Clin Psychiatry, 2003, 64 Suppl 18: 8-13.
    [28] Hammarback S, Damber JE, Backstrom T.Relationship between symptom severity and hormone changes in women with premcnstrual syndrome[J]. Clin Endocrinol Metab, 1989, 68(1): 125-30.
    [29] Thompson KN, Kulkami J, Sergejew AA. Extra pyramidal symptoms and estrogen[J]. Acta Psychiatr Scand, 2000, 101: 130-134.
    [30] Rupprccht R, Michclc F, Hermann B, et al. Neuroactive steroids: molecular mechanisms of action and implications for neuropsychopharmacology[J]. Brain Res Rev, 2001, 37(1-3): 59-67.
    [31] Honjo H, Kikuchi N, Hosoda T, et al. Alzheimer's disease and estrogen[J]. Steroid Biochem Mol Biol, 2001, 76(1-5): 227-230.
    [32] McEwen BS, Alves SE. Estrogen actions in the central nervous system[J]. Endocr Rev, 1999, 20: 279-307.
    [33] Woollcy CS. Effects of estrogen in the CNS[J]. Curr Opin Neurobiol, 1999, 9: 349-354.
    [34] Wihlback AC, Sundstrom Poromaa I, Bixo M, Allard P, Mjorndal T, Spigset O. Influence of menstrual cycle on platelet serotonin uptake site and serotonin2A receptor binding[J]. Psychoneuroendocrinology, 2004 Jul; 29(6): 757-766.
    [35] 张玉勤.经前期综合征病理生理学研究[J].国外医学情报,1998,19(6):37-38.
    [36] Pandcy GN, Pandcy SC; et al. Platclet serotonin 2A receptors: A potential biological marker for suicidal behavior[J]. Am J Psychiatry, 1995, 152: 853.
    [37] Lu NZ, Eshleman A J, Janowsky A, etal. Ovarian steroid regulation of serotonin reuptake transporter(SERT) binding distribution and function in female macaques[J]. Mol Psychiatry, 2003, 8: 353-360.
    [38] Hsiao CC, Liu CY, Hsiao MC. No correlation of depression and anxiety to plasma estrogen and progesterone levels in patients with premenstrual dysphoric disorder[J]. Psychiatry Clin Neurosci, 2004, 58(6): 593-599.
    [39] A.B. Hcinrich, O.T. Wolf. Investigating the Effects of Estradiol or Estradiol/Progesterone Treatment on Mood, Depressive Symptoms, Menopausal Symptoms and Subjective Sleep Quality in Older Healthy Hysterectomized Women: A Questionnaire Study[J]. Neuropsychobiology, 2005, 52 (1): 17-23.
    [40] Prior JC, McKay DW, Alojado N, Vigna YM. No adverse effects of medroxy progesterone treatment without estrogen in postmenopausal women: double-blind, placebo controlled, crossover trial. Obstet Gynecol 1994, 83: 24-28.
    [41] INGER B J(?) RN, INGER SUNDSTR(?) M-POROMAA, MARIE BIXO, etal. Increase of Estrogen Dose Deteriorates Mood during Progcstin Phase in Sequential Hormonal Therapy[J]. Clin Endocrinol Metab, 2003, 88(5): 2026-2030.
    [42] Dahr V, Murphy BE. The premenstrual syndrome and its treatment [J]. Steroid Biochem Mol Biol, 1991, 39: 275-251.
    [43] 汪广剑.雌激素与情感障碍的相关研究[J].国外医学精神病学分册,1999,26(4):226-229.
    [44] 喻东山.抑郁症的生物级联.四川精神卫生[J].2000,13(2):138-141.
    [45] 江开达.精神医学新概念[M].上海:复旦大学出版社,2004,6:170.
    [46] 蔡焯基,汤宜朗,马辛.抑郁症基础与临床[M].北京:科学出版社,2001,5:38.
    [47] Lucki I. The spectrum of behaviors influenced by serotonin[J]. Biol Psychiatry, 1998, 44(2): 151.
    [48] Hensler JG. Regulation of 5-HT_(1A) receptor function in brain following agonist or antidepressant administration[J]. Life Sci, 2003, 72: 1665-1682.
    [49] Sargent PA, kjaer KH, Bench CJ, et al. Brain serotonin1A receptor binding measured by positron emission tomography with[~(11)C] WAY-100635: Effects of depression and antidepressant treatment [J]. Arch Gen Psychiatry, 2000, 57: 174-180.
    [50] 许晶,刘效巍,左萍萍,等.慢性应激抑郁模型大鼠海马5-HT1A受体的变化[J].大连医科大学学报,2002,24(2):84-87.
    [51] 蔡伟,谢青,谢敬东,等.5-羟色胺受体-1a在干扰素诱导抑郁症中的作用[J].上海第二医科大学学报,2005,25(3):252-255.
    [52] Lopez-Figueroa AL, Norton CS, Lopez-Figueroa MO, Armellini-Dodel D, Burke S, Akil H, Lopez IF, Watson SJ. Serotonin 5-HT1A, 5-HTIB, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia[J]. Biol Psychiatry, 2004, 55(3): 225-233.
    [53] Barues, NM, Sharo T.A review of central 5-HT receptors and their function. Neuropharmacology, 1999, 38: 1083-1152.
    [54] 陈芳萍,李运曼,刘国卿.5-HT_(1A)受体激动剂类抗抑郁药的研究与开发[J].药学进展,2003,7(4):213-216.
    [55] Tajima O. Pharmacotherapy for anxiety disorders[J]. Seishin Shinkeigaku Zasshi, 2004, 106 (10): 1283-1289.
    [56] 高霄飞,王雪琦,何成.抑郁症单胺类递质受体研究进展[J].生理学进展,2002,33(1):17-20.
    [57] Pineyo G, Blier P. Autoreguiation of serotonin neurons: role in antidepressant drug action [J]. Pharamcol Rev, 1999, 51(3): 534-591.
    [58] Ferrier IN, Mckeith IG, Gross AJ. et al. Postmorterm neurochemical studies in depression[J]. Ann NY. Acad Sei, 1986, 487: 128.
    [59] 蔡焯基,汤宜朗,马辛.抑郁症基础与临床[M].北京:科学出版社,2001,5:35.
    [60] 汪卫华,王焕林,孙剑.抗抑郁药的药理研究进展[J].国外医学·精神卫生分册,1997,(3):154-158.
    [61] SibilleE, Samyai Z, Benjamin D, Gal J, Baker H, TothM. Antisense inhibition of 5-hydroxytryptamine 2a receptor induces an antidepressant-like effect in mice[J]. Mol Pharmacol, 1997, 52 (6): 1056-1063.
    [62] 雷艳青,郭田生.5-羟色胺在精神分裂症病理生理及其治疗中的作用[J].国外医学精神病学分册,1998,25(2):95-99.
    [63] 苏颖,刘晓民.5-羟色胺2A受体基因与疾病的关系[J].中国综合临床,2003,19(9):771-772.
    [64] Sprouse JS, Wikinson LO. Innovative therapeutic action by targeting serotonin 1A receptors selectively[J]. Int Rev Psychiatry, 1995, 7(1): 5.
    [65] Cesura AM, Imhof R, Muggli-Maniglio D, et al. Characterization of ~3H Ro 16-6491 binding to digitonin solubilized monoamine oxidase-B and purification of the enzyme from human platelets by affinity chromatography[J]. Biochem Pharmacnl, 1990, 39: 216.
    [66] Chatterjee SS, Bhattacharrya SK, Wonnemann M, etal. Hyperforin as a possible antidepressant component of Hypericum extracts[J]. Life Sci, 1998, 63(6): 499-510.
    [67] Cruces MA, Elorriage C, Fermandez-Alvarez E. The kinetics of monoamine oxidase inhibition by three 2-indolylmethyamine derivatives[J]. Biochem Pharmacol, 1990, 40: 535.
    [68] Olanow CW. MAO-B inhibitors in Parkinson's disease[J]. Adv Neurol, 1993, 60: 666.
    [69] Blank AM, Goldstein SE, Chatterjee N. Pre-menstrual tension and mood change[J]. Can Psychiatry. 1980, 25(7): 577-85.
    [70] Ashby CR Jr, Carr LA, Cook CL, Steptoe MM, Franks DD. Alteration of platelet serotonergic mechanisms and monoamine oxidase activity in premenstrual syndrome[J]. Biol Psychiatry, 1988, 24(2): 225-33.
    [71] Chakravorty SG, Halbreich U. The influence of estrogen on monoamine oxidase activity[J]. Psychoneuroendocrinology Bull, 1997, 33(2): 229-233.
    [72] Gundlah C, Lu NZ, Bethea CL. Ovarian steroid regulation of monoamine oxidase-A and -B mRNAs in the macaque dorsal raphe and hypothaiamic nuclei[J] Psychopharmacology (Berl), 2002, 160(3): 271-282.
    [73] Lotufo-Neto F, Trivedi M, Thase ME. Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the treatment of depression [J]. Neuropsychopharmacology, 1999, 20 (3): 226-247.
    [74] Fioroni L, Andrea GD, Alecci M, Cananzi A, Facchinetti F. Platelet serotonin pathway in menstrual migraine[J]. Cephalalgia, 1996, 16(6): 427-430.
    [75] Ashby CR Jr, Carr LA, Cook CL, Steptoe MM, Franks DD. Effect of plasma from premenstrual syndrome and control patients on human platelet and rat brain synaptosome monoamine oxidase B aetivity[J]. Neuropsychobiology, 1992; 25(3): 121-125.
    [76] Hallman J, Oreland L, Edman G, Schailing D. Thromboeyte monoamine oxidase activity and personality traits in women with severe premenstrual syndrome[J]. Acta Psychiatr Scand. 1987, 76(3): 225-234.
    [77] 周凤梧,张灿玾.黄帝内经素问语释[M].济南:山东科学技术出版社,1985,10:861.
    [78] 李克光.金匮要略讲义[M].上海:上海科学技术出版社,1985,10:250.
    [79] 朱震亨.丹溪治法心要[M].济南:山东科学技术出版社,1985,16.
    [80] 虞抟.医学正传[M].北京:人民卫生出版社,1965,4:85.
    [81] 徐春圃.古今医统大全[M].北京:人民卫生出版社,1991,8:939.
    [82] 张介宾.景岳全书(上册)[M].上海:上海科学技术出版社,1984,5:356.
    [83] 李用粹.证治汇补[M].北京:中国中医药出版社,1999,1:85.
    [84] 张隐庵.黄帝内经素问集注[M].上海:上海科学技术出版社,1980,4:357.
    [85] 黄英志.叶天士医学全书[M].北京:中国中医药出版社,1999,8:174.
    [86] 张璐.张氏医通[M].北京:中国中医药出版社,1995,6:51.
    [87] 王新华,潘秋翔.中医历代医话精选[M].南京:江苏科学技术出版社,1998,3:1052.
    [88] Mortola JF. Issues in the diagnosis and research of premenstrual symptoms[J]. Clin Obstet Gynecol, 1992, 35: 587-598.
    [89] 龚绍麟.抑郁症[M].北京:人民卫生出版社,2003,2:22.
    [90] 姜佐宁.现代精神病学[M].北京:科学出版社,2004,3:346.
    [91] 翟书涛.妇女精神卫生[M].北京:人民卫生出版社,1999,7:129.
    [92] 丰有吉,沈铿.妇产科学[M].北京:人民卫生出版社,2005,8:238.
    [93] 曹缵孙,陈晓燕.妇产科综合征[M].北京:人民卫生出版社,2003,11:110-111
    [94] 文哲双,王志忠,朱毅.肝郁患者血清T、E2、PRL检测及临床意义[J].湖北中医学院学报,2000,2(2):27-29.
    [95] 王霞灵,周大桥,李延福.肝郁患者雌激素水平研究[J].湖北中医杂志,1996,18(4):38-39.
    [96] 杨士友,黄世福,孙备.解百忧口服液对抑郁模型大鼠行为及中枢神经递质的影响[J].中国中医基础医学杂志,2000,6(11):56-59.
    [97] 畅洪昇,王庆国,石任兵,等.四逆散活性成分对抑郁症大鼠慢性应激模型行为学及脑内单胺类神经递质的影响[J].北京中医药大学学报,2003,26(5):42-45.
    [98] 郝世凤.女性肝郁状态下神经递质、激素的实验研究.成都中医药大学硕士学位论文集.2004.
    [99] 陈淑涛.肝郁型经前期综合征的临床观察及实验结果分析.成都中医药大学硕士学位论文集.2004.
    [100] 相宇.经轻胶囊治疗高雌激素导致的类经前期综合征的实验研究.成都中医药大学博士学位论文集.2004.
    [101] 相宇,郝世凤,陈淑涛,等.经轻胶囊对类经前期综合征动物模型病理状态干预作用的研究[J].中国中医药科技,2005,12(4):218-220.
    [102] Tiller Jwc. Clinical overview of moclobemide[J]. Prog Neuropsychopharmacol Biol Psychiatry, 1993, 17: 703.
    [103] 吕路线,郭本玉,赵靖平.吗氯贝胺治疗抑郁症[J].中国新药与临床杂志,2001,20(1):16-18.
    [104] Farvolden P, Kennedy SH, Lam RW. Recent developments in the psychobiology and pharmacotherapy of depression; optimising existing treatments and novel approaches for the future [J]. Expert Opin Investig Drugs, 2003, 12: 65-86.
    [105] Celada P, Puig M, Amargos-Bosch M, Adell A, Artigas F. The therapeutic role of 5-HT1A and 5-HT2A receptors in depression[J]. Psychiatry Neurosci, 2004 Jul; 29(4): 252-265.
    [106] 李晓东.盐酸舍曲林获FDA许可用于经前焦虑障碍的治疗[J].国外医药·合成药·生化药·制剂分册,2002,23(4):246.
    [107] VaugeoisJM, Passera G, Zuccaro F, Costentin J. Individual differences in response to imipramine in the mouse tail suspension test[J]. Psychopharmacology, 1997, 134 (4): 387-391.
    [108] 吕俊华,钟玲.实验性抑郁动物模型的评价[J].中国病理生理杂志,2001,17(9):916-919.
    [109] 陈小野,蒋小丽,邹世洁,等.雌激素对大鼠中医体质影响的研究[J].现代中西医结合杂志,2005,14(18):2383-2385.
    [110] Darmni NA, Reeves SL. The mechanism: by which the selective 5-HT_(1A) receptor antagonist S-(-)-UH301 produces head-twitches in mice[J]. Pharmacol Biochem Behav, 1996, 55(1): 1-10.
    [111] 朱紫青,季建林,肖世富.抑郁障碍诊疗关键[M].南京:江苏科学技术出版社,2003,10:23.
    [112] 龚绍麟.抑郁症[M].北京:人民卫生出版社,2003,2:139.
    [113] 曹泽毅,翁梨驹主编.中华妇产科手册[M].济南:山东科学技术出版社,1998,7:207.
    [114] 禁焯基,汤宜朗,马辛.抑郁症基础与临床[M]北京:科学出版社,2001,5:201.

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