雌二醇导致经行头痛的实验及经轻胶囊干预机制初探
|
摘要
目的:观察分析用实验手段复制经行头痛的病理生理状态,同时整合中医调经与止痛的优势对之加以干预,以探讨本病病因及中药治疗。
方法:选择3～4月龄雌性SD大鼠,设立空白对照组、硝酸甘油模型对照组、雌激素模型组、雌激素+甲基睾丸素组、雌激素+阿司匹林组、雌激素+经轻胶囊高剂量组、雌激素+经轻胶囊低剂量组。通过对动物按只观察,逐只建立动物动情周期档案,选择动物动情期给予造模刺激,观察苯甲酸雌二醇皮下注射对实验大鼠阴道角化细胞指数,大脑皮层、血浆前列腺素E_2,血浆降钙素基因相关肽,硬脑膜组织形态,三叉神经核P物质、一氧化氮合成酶及c-fos表达的影响,并用硝酸甘油复制头痛的阳性模型来评价本实验雌二醇造模的成功。同时通过对血清雌二醇、孕酮、睾酮、催乳素及前述指标的考察,探讨中药经轻胶囊的可能干预机制。
结果:外源性雌激素可造成实验鼠持续高阴道角化细胞指数,升高大脑皮层、血浆前列腺素E_2、血浆降钙素基因相关肽含量,使三叉神经核P物质、一氧化氮合成酶、c-fos表达增强,并使硬脑膜血管扩张、血管周围组织炎性水肿明显、血管周围细胞数目增多。上述病理变化与阳性模型硝酸甘油模型对照有趋同性。中药经轻胶囊可降低过高的阴道角化细胞指数、血清雌二醇、雌二醇/孕酮、催乳素,减少大脑皮层、血浆前列腺素E_2,血浆降钙素基因相关肽含量,恢复三叉神经核P物质、一氧化氮合成酶及c-fos表达水平,改善硬脑膜血管扩张及组织水肿。
结论:在大鼠动情期给予外源性雌二醇刺激可出现头痛的特异性指征,并导致痛性的支持性指标发生阳性改变,与经行头痛的病因及临床表现贴近;经轻胶囊可降低体内过高雌激素水平,改善以上病理变化。
OBJECTIVE: Observe and analyze the pathological and physiological state of menstrual headache which is made by the experimental method. At the same time combine the treatment to the advantage of TCM which regulates menses and stops pain. Discuss the pathogenic factors and treatment of herbs. METHOD: Divided SD rats aged at 3-4months into seven groups, such as group of contrast, Nitroglycerin, Estradiol, Estradiol with methyl testosterone, Estradiol with Aspirin model, Estradiol with Jingqing Capsule with great dose and Estradiol with Jingqing Capsule with little dose. Through setting up the files of estrous cycle individually and make the models during the estrous period, observe if subcutaneous injection of estradiol benzoate can effect the experimental rats' following indexes such as the index of vaginal keratinocyte, prostaglandin E_2 of pallium and plasm, calcitonin-gene-related peptide(CGRP) of plasm, organic modality of endocranium, expression of Substance P, nitricoxide synthase and c-fos of trigeminal Nucleus, and testify the success of Estradiol model by comparing with the positive Nitroglycerin model. Explore the possible tampering function of Jingqing Capsule by the evaluation on Estradiol, progestin, testosterone and prolactin. RESULTS: Exogenetic estradiol can lift the index of vaginal keratinocyte and increase prostaglandin E_2 of pallium and plasm, calcitonin-gene-related peptide(CGRP) of plasm; strengthen expression of Substance P, nitricoxide synthase and c-fos of trigeminal Nucleus, and cause hemangiectasis of endocranium, obvious circumvascular inflammatory edema and circumvascular hyperplastic cells. All the pathological change is the same as the Nitroglycerin model group. Jingqing Capsule can reduce the index of vaginal keratinocyte, serous estradiol, progesterone, prolactin, prostaglandin E_2 of pallium and plasm, calcitonin-gene-related peptide(CGRP) of plasm, restore expression of the substance P, nitricoxide
方法:选择3～4月龄雌性SD大鼠,设立空白对照组、硝酸甘油模型对照组、雌激素模型组、雌激素+甲基睾丸素组、雌激素+阿司匹林组、雌激素+经轻胶囊高剂量组、雌激素+经轻胶囊低剂量组。通过对动物按只观察,逐只建立动物动情周期档案,选择动物动情期给予造模刺激,观察苯甲酸雌二醇皮下注射对实验大鼠阴道角化细胞指数,大脑皮层、血浆前列腺素E_2,血浆降钙素基因相关肽,硬脑膜组织形态,三叉神经核P物质、一氧化氮合成酶及c-fos表达的影响,并用硝酸甘油复制头痛的阳性模型来评价本实验雌二醇造模的成功。同时通过对血清雌二醇、孕酮、睾酮、催乳素及前述指标的考察,探讨中药经轻胶囊的可能干预机制。
结果:外源性雌激素可造成实验鼠持续高阴道角化细胞指数,升高大脑皮层、血浆前列腺素E_2、血浆降钙素基因相关肽含量,使三叉神经核P物质、一氧化氮合成酶、c-fos表达增强,并使硬脑膜血管扩张、血管周围组织炎性水肿明显、血管周围细胞数目增多。上述病理变化与阳性模型硝酸甘油模型对照有趋同性。中药经轻胶囊可降低过高的阴道角化细胞指数、血清雌二醇、雌二醇/孕酮、催乳素,减少大脑皮层、血浆前列腺素E_2,血浆降钙素基因相关肽含量,恢复三叉神经核P物质、一氧化氮合成酶及c-fos表达水平,改善硬脑膜血管扩张及组织水肿。
结论:在大鼠动情期给予外源性雌二醇刺激可出现头痛的特异性指征,并导致痛性的支持性指标发生阳性改变,与经行头痛的病因及临床表现贴近;经轻胶囊可降低体内过高雌激素水平,改善以上病理变化。
OBJECTIVE: Observe and analyze the pathological and physiological state of menstrual headache which is made by the experimental method. At the same time combine the treatment to the advantage of TCM which regulates menses and stops pain. Discuss the pathogenic factors and treatment of herbs. METHOD: Divided SD rats aged at 3-4months into seven groups, such as group of contrast, Nitroglycerin, Estradiol, Estradiol with methyl testosterone, Estradiol with Aspirin model, Estradiol with Jingqing Capsule with great dose and Estradiol with Jingqing Capsule with little dose. Through setting up the files of estrous cycle individually and make the models during the estrous period, observe if subcutaneous injection of estradiol benzoate can effect the experimental rats' following indexes such as the index of vaginal keratinocyte, prostaglandin E_2 of pallium and plasm, calcitonin-gene-related peptide(CGRP) of plasm, organic modality of endocranium, expression of Substance P, nitricoxide synthase and c-fos of trigeminal Nucleus, and testify the success of Estradiol model by comparing with the positive Nitroglycerin model. Explore the possible tampering function of Jingqing Capsule by the evaluation on Estradiol, progestin, testosterone and prolactin. RESULTS: Exogenetic estradiol can lift the index of vaginal keratinocyte and increase prostaglandin E_2 of pallium and plasm, calcitonin-gene-related peptide(CGRP) of plasm; strengthen expression of Substance P, nitricoxide synthase and c-fos of trigeminal Nucleus, and cause hemangiectasis of endocranium, obvious circumvascular inflammatory edema and circumvascular hyperplastic cells. All the pathological change is the same as the Nitroglycerin model group. Jingqing Capsule can reduce the index of vaginal keratinocyte, serous estradiol, progesterone, prolactin, prostaglandin E_2 of pallium and plasm, calcitonin-gene-related peptide(CGRP) of plasm, restore expression of the substance P, nitricoxide
引文
[1] 孙宏丽.中药治疗经前偏头痛48例[J].新中医,2003,35(2):52-53.
[2] 程昭寰,主编.中医脑病现代研究进展[M].北京:专利文献出版社,1998,151-153.
[3] 黄美珍.辨证治疗经期头痛30例[J].四川中医,2000,18(7):39-40.
[4] 钟健峰,陈瑛瑛.经行头痛从肝论治[J].新中医,2001,33(3):70.
[5] 曹宁芳,秦中垠.川芎汤治疗经前头痛105例临床观察[J].陕西中医学院学报,2001,24(5):40.
[6] 李仪奎,主编.中药药理实验方法学[M].上海:上海科学技术出版社(第一版),1991:224-228.
[7] 王淑贞,主编.实用妇产科学[M].北京:人民卫生出版社,1995,807.
[8] 任永欣,彭成,姚干.头风饮对实验性偏头痛动物模型c-fos、c-jun基因表达的影响[J].成都中医药大学学报,2000,23(3):34-36.
[9] 周明眉.大川芎方的物质基础与作用机理研究.成都中医药大学博士学位论文集,2002:58.
[10] 王伯儒,等主编.病理学技术[M].北京:人民卫生出版社,2000,65.
[11] 黄国平,马传庚,徐叔云.维拉帕米、硝苯吡啶和粉防已碱加强吲哚美辛的镇痛作用[J].中国药理学通报,1993:9(1):36.
[12] 张培林等.神经解剖学[M].北京:人民卫生出版社,1987.
[13] 刘敏如,谭万信,主编.中医妇产科学[M].北京:人民卫生出版社,2001,371-375.
[14] 陈群主编.头痛调治[M].广州:广东科技出版社,2003,1—10.
[15] Marcus DA. Interrelationships of neurochemicals, estrogen, and recurring headache[J]. Pain, 1995, 62 (2): 129-139.
[16] Dan TT, Knight K, Ton-That V. Modulation ofmyofascial pain by the reproductive hormones: a prelinminary report[J]. J Prosthet Dent, 1998, 79 (6): 663-670.
[17] LeResche L, Saunders K, Von KorffMR, et al. Use of exogenous hormones and risk of tempormandibulardisorderpain[J]. Pain, 1997, 69 (1-2): 153-160.
[18] Brynhildsen JO, Bjors E, Skarsgard C, et al. Is hormone replacement therapy a risk factor for low back pain among postmenopausal women? [J] Spine, 1998; 23(7): 809-813.
[19] Guicheney P, Leger D, Barrat J, et al. Platelet serotonin content and plasma tryptophan in peri- and postmenopausal women: variations with plasma oestrogen levels and depressive symptoms[J]. Eur J Clin Invest, 1988, 18(3): 297-304.
[20] Ernberg M, Hedenberg-Magnusson B, Alstergren P, et al. Pain, allodynia, and serum serotonin level in orofacial pain of muscular origin[J]. J Orofac Pain, 1999, 13 (1): 56-62.
[21] 黄帝内经.北京:人民卫生出版社,1963,24.
[22] 刘奉五主编.刘奉五妇科经验[M].北京:人民卫生出版社,1982,9.
[23] 叶天士.临证指南医案.上海:上海科学技术出版社,1991,666.
[24] 唐容川.血证论.上海:上海科技出版社,1995,8.
[25] 张景岳.妇人规.广州:广东科技出版社,1984,1:26.
[26] 孙文胤.丹台玉案(下册·第五卷).上海:上海科学技术出版社,1984,42.
[27] 孙思邈.孙真人千金方.北京:人民卫生出版社,1996,10:23.
[28] 张璐.张氏医通.北京:中国中医药出版社,1995,6:51.
[29] 郭霭春.黄帝内经灵枢校注语释.天津:天津科学技术出版社,1989,431.
[30] 朱震亨.丹溪治法心要.济南:山东科学技术出版社,1985,16.
[31] 张介宾.景岳全书(上册).上海:上海科学技术出版社,1984,5:356.
[32] 赵献可.医贯.北京:学苑出版社,1996,55.
[33] 成都中医学院妇科教研室.中医妇科学.北京:人民卫生出版社,1986,44-45.
[34] 乔明琦,张继忠,马成海,等.猕猴模拟经前期综合征肝气逆症病变的可行性探索[J].中国中医基础医学杂志,1998,4(6):28-31.
[35] 刘秀霞,孙艳红,郑宇.经前平颗粒[J].中国新药杂志,2002,2(11):174.
[36] 狄留庆,谢辉,朱荃,等.镇静逍遥颗粒的药效学研究[J].中药新药与临床药理,2000,11(1):32-35.
[37] 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2001级学位论文集,2001.
[38] 郑怀美,主编.现代妇产科学[M].上海:上海医科大学出版社(第一版),1998,18.
[39] 曹泽毅,翁梨驹,主编.中华妇产科临床手册[M].山东:山东科学技术出版社(第一版),1998:207
[40] Kaplan CR, Eddy CA, Olive DL, et al. Effect of ovarian endometriosis on ovulation in rabbits[J]. Am J Obstet Gynecol, 1989, 160(1): 40-44.
[41] 施新猷,主编.医用实验动物学[M].陕西:陕西科学技术出版社,1989,33-39.
[42] 魏泓,主编.医学实验动物学[M].四川:四川科学技术出版社(第8版),1998,164.165.
[43] 彭成,罗光宇.脾气虚脾不统血证候动物模型的研究思路[J].中医杂志,1996,37(4):241.
[44] Moskowitz MA. Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine[J].TrendsPharmacolSci, 1992, 13 (8): 307-311.
[45] 陈磊,王怀良,刑军,等.植物药生物碱94-95-10L对大鼠CSD模型脑内c-fos基因表达的影响[J].中国医科大学学报,2000,29(3):172-174.
[46] 杜力军,孙虹,李敏,等.精制吴茱萸胶囊对偏头痛小鼠的作用[J].中药药理与临床,1999:15(3):3-4.
[47] Olesen J, Thomsen LL, Lassen LH, et al. The nitric oxide hypothesis of migraine and other vascular headaches[J]. Cephalalgia, 1995, 15 (2): 94—100.
[48] 阎海主编.偏头痛诊治大成[M].北京:学苑出版社,1996,68-69.
[49] 贾新权,张宗旺.前列腺素在脊髓水平痛信息处理中的作用[J].中国麻醉与镇痛,2004,6(2):143-146.
[50] 翟文杰.苯噻啶与消炎痛联合治疗偏头痛[J].综合临床医学,1994,10(2):106-107.
[51] 杨友华.氟桂利嗪、阿司匹林联用治疗偏头痛[J].中国乡村医药杂志,2004,11(2):13—14.
[52] 贺小平.西比灵合用小剂量阿司匹林治疗偏头痛疗效观察[J].成都医药,2003,29(4):220-221
[53] Horrobin DF, Manku MS. Are methyl xanthines used as phosphodiesterase inhibitors also prostaglandin antagonists[proceedings] ? [J]. J Physiol, 1977, 266 (1): 60-61.
[54] Buzzi MG, Moskwitz MA. The trigemino-vascular system and migraine[J] . Pathol Biol(Paris), 1992, 40(4): 313-317.
[55] van Rossum D, Hanisch UK, Quirion R. Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors[J]. Neurosci BiobehavRev, 1997, 21 (5): 649-678.
[56] Durham PL, Russo A. New insights into the molecular actions of serotonergic antimigraine drugs[J]. Pharmacol Therapeutics, 2002, 94 (1-2): 77-92.
[57] 王洪欣,孙远标,朱士文等.降钙素基因相关肽与偏头痛关系的研究[J].脑与神经疾病杂志,2003,11(1):53.
[58] 肖峰,沈雪峰,杨士军等.偏头痛患者血浆内皮素和降钙素基因相关肽含量的变化与临床意义[J].神经疾病与精神卫生,2002,2(1):29-30.
[59] 李炜,邓干初,刘远珍等.针刺肝胆经穴治疗偏头痛207例临床研究[J].中医杂志,2002,43(11):824-825.
[60] 闫国平,赵晏.P物质参与痛觉调控的研究进展[J].国外医学生理、病理科学与临床分册,1996,16(3):195-197.
[61] 王宇卉,曹文辉.偏头痛的生化研究进展[J].国外医学:神经病学·神经外科学分册,1994,21(2):71—75.
[62] 刘晓萍,徐珞,于业军等.大剂量雌二醇对大鼠血浆和组织中P物质和锌离子含量的影响[J].中国高血压杂志,1995,3(1):21-22.
[63] 刘晓萍,徐珞,于业军等.雌激素诱发大鼠免疫器官退化及与P物质关系的研究[J].河南医科大学学报,1995,30(4):393-395.
[64] Olesen J, Thomsen LL, Iversen H. Nitric oxide is a key molecule in migraine and other vascular headaches[J]. TrendsPharmacolSci, 1994, 15(5): 149-153.
[65] Bellantonio P, Micieli G, Buzzi MG, et al. Haemodynamic correlates of early and delayed responses to sublingual administration of isosorbide dinitrate in migraine patients: a transcranial Doppler study[J]. Cephalalgia, 1997, 17 (3): 183-187.
[66] 连亚军,王左生,邱亚峰等.头痛患者血浆一氧化氮和降钙素基因相关肽含量测定[J].河南医科大学学报,1998,33(2):64-66.
[67] Tan DY, Zhang LZ, Zhao YT, et al. Involvement of nitric oxide in the vasodilator and depressor effect ofcalcitonin gene-related peptide[J]. Chin Med J, 1994, 107(10): 745-749.
[68] Fozard JR. The 5-hydroxytryptamine-nitric oxide connection: the key link in the initiation of migraine[J]. Arch Int Pharmacodyn Ther, 1995, 329 (1): 111-119.
[69] Imthurn B, Rosselli M, JaegerAW, et al. Differential effects of hormone-replacement therapy on endogenous nitric oxide(nitrite/nitrate) levels in postmenopausal women substituted with 1713-estradiol valerate and cyproterone acetate or medroxyprogesterone acetate[J]. J Clin EndocrinolMetab, 1997, 82(2): 388-394.
[70] 张锁龙,吴国球,凌玲等.17β-雌二醇对ox-LDL诱导内皮细胞一氧化氮生成的影响[J].中国心血管杂志,2001,6(6):313-316.
[2] 程昭寰,主编.中医脑病现代研究进展[M].北京:专利文献出版社,1998,151-153.
[3] 黄美珍.辨证治疗经期头痛30例[J].四川中医,2000,18(7):39-40.
[4] 钟健峰,陈瑛瑛.经行头痛从肝论治[J].新中医,2001,33(3):70.
[5] 曹宁芳,秦中垠.川芎汤治疗经前头痛105例临床观察[J].陕西中医学院学报,2001,24(5):40.
[6] 李仪奎,主编.中药药理实验方法学[M].上海:上海科学技术出版社(第一版),1991:224-228.
[7] 王淑贞,主编.实用妇产科学[M].北京:人民卫生出版社,1995,807.
[8] 任永欣,彭成,姚干.头风饮对实验性偏头痛动物模型c-fos、c-jun基因表达的影响[J].成都中医药大学学报,2000,23(3):34-36.
[9] 周明眉.大川芎方的物质基础与作用机理研究.成都中医药大学博士学位论文集,2002:58.
[10] 王伯儒,等主编.病理学技术[M].北京:人民卫生出版社,2000,65.
[11] 黄国平,马传庚,徐叔云.维拉帕米、硝苯吡啶和粉防已碱加强吲哚美辛的镇痛作用[J].中国药理学通报,1993:9(1):36.
[12] 张培林等.神经解剖学[M].北京:人民卫生出版社,1987.
[13] 刘敏如,谭万信,主编.中医妇产科学[M].北京:人民卫生出版社,2001,371-375.
[14] 陈群主编.头痛调治[M].广州:广东科技出版社,2003,1—10.
[15] Marcus DA. Interrelationships of neurochemicals, estrogen, and recurring headache[J]. Pain, 1995, 62 (2): 129-139.
[16] Dan TT, Knight K, Ton-That V. Modulation ofmyofascial pain by the reproductive hormones: a prelinminary report[J]. J Prosthet Dent, 1998, 79 (6): 663-670.
[17] LeResche L, Saunders K, Von KorffMR, et al. Use of exogenous hormones and risk of tempormandibulardisorderpain[J]. Pain, 1997, 69 (1-2): 153-160.
[18] Brynhildsen JO, Bjors E, Skarsgard C, et al. Is hormone replacement therapy a risk factor for low back pain among postmenopausal women? [J] Spine, 1998; 23(7): 809-813.
[19] Guicheney P, Leger D, Barrat J, et al. Platelet serotonin content and plasma tryptophan in peri- and postmenopausal women: variations with plasma oestrogen levels and depressive symptoms[J]. Eur J Clin Invest, 1988, 18(3): 297-304.
[20] Ernberg M, Hedenberg-Magnusson B, Alstergren P, et al. Pain, allodynia, and serum serotonin level in orofacial pain of muscular origin[J]. J Orofac Pain, 1999, 13 (1): 56-62.
[21] 黄帝内经.北京:人民卫生出版社,1963,24.
[22] 刘奉五主编.刘奉五妇科经验[M].北京:人民卫生出版社,1982,9.
[23] 叶天士.临证指南医案.上海:上海科学技术出版社,1991,666.
[24] 唐容川.血证论.上海:上海科技出版社,1995,8.
[25] 张景岳.妇人规.广州:广东科技出版社,1984,1:26.
[26] 孙文胤.丹台玉案(下册·第五卷).上海:上海科学技术出版社,1984,42.
[27] 孙思邈.孙真人千金方.北京:人民卫生出版社,1996,10:23.
[28] 张璐.张氏医通.北京:中国中医药出版社,1995,6:51.
[29] 郭霭春.黄帝内经灵枢校注语释.天津:天津科学技术出版社,1989,431.
[30] 朱震亨.丹溪治法心要.济南:山东科学技术出版社,1985,16.
[31] 张介宾.景岳全书(上册).上海:上海科学技术出版社,1984,5:356.
[32] 赵献可.医贯.北京:学苑出版社,1996,55.
[33] 成都中医学院妇科教研室.中医妇科学.北京:人民卫生出版社,1986,44-45.
[34] 乔明琦,张继忠,马成海,等.猕猴模拟经前期综合征肝气逆症病变的可行性探索[J].中国中医基础医学杂志,1998,4(6):28-31.
[35] 刘秀霞,孙艳红,郑宇.经前平颗粒[J].中国新药杂志,2002,2(11):174.
[36] 狄留庆,谢辉,朱荃,等.镇静逍遥颗粒的药效学研究[J].中药新药与临床药理,2000,11(1):32-35.
[37] 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2001级学位论文集,2001.
[38] 郑怀美,主编.现代妇产科学[M].上海:上海医科大学出版社(第一版),1998,18.
[39] 曹泽毅,翁梨驹,主编.中华妇产科临床手册[M].山东:山东科学技术出版社(第一版),1998:207
[40] Kaplan CR, Eddy CA, Olive DL, et al. Effect of ovarian endometriosis on ovulation in rabbits[J]. Am J Obstet Gynecol, 1989, 160(1): 40-44.
[41] 施新猷,主编.医用实验动物学[M].陕西:陕西科学技术出版社,1989,33-39.
[42] 魏泓,主编.医学实验动物学[M].四川:四川科学技术出版社(第8版),1998,164.165.
[43] 彭成,罗光宇.脾气虚脾不统血证候动物模型的研究思路[J].中医杂志,1996,37(4):241.
[44] Moskowitz MA. Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine[J].TrendsPharmacolSci, 1992, 13 (8): 307-311.
[45] 陈磊,王怀良,刑军,等.植物药生物碱94-95-10L对大鼠CSD模型脑内c-fos基因表达的影响[J].中国医科大学学报,2000,29(3):172-174.
[46] 杜力军,孙虹,李敏,等.精制吴茱萸胶囊对偏头痛小鼠的作用[J].中药药理与临床,1999:15(3):3-4.
[47] Olesen J, Thomsen LL, Lassen LH, et al. The nitric oxide hypothesis of migraine and other vascular headaches[J]. Cephalalgia, 1995, 15 (2): 94—100.
[48] 阎海主编.偏头痛诊治大成[M].北京:学苑出版社,1996,68-69.
[49] 贾新权,张宗旺.前列腺素在脊髓水平痛信息处理中的作用[J].中国麻醉与镇痛,2004,6(2):143-146.
[50] 翟文杰.苯噻啶与消炎痛联合治疗偏头痛[J].综合临床医学,1994,10(2):106-107.
[51] 杨友华.氟桂利嗪、阿司匹林联用治疗偏头痛[J].中国乡村医药杂志,2004,11(2):13—14.
[52] 贺小平.西比灵合用小剂量阿司匹林治疗偏头痛疗效观察[J].成都医药,2003,29(4):220-221
[53] Horrobin DF, Manku MS. Are methyl xanthines used as phosphodiesterase inhibitors also prostaglandin antagonists[proceedings] ? [J]. J Physiol, 1977, 266 (1): 60-61.
[54] Buzzi MG, Moskwitz MA. The trigemino-vascular system and migraine[J] . Pathol Biol(Paris), 1992, 40(4): 313-317.
[55] van Rossum D, Hanisch UK, Quirion R. Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors[J]. Neurosci BiobehavRev, 1997, 21 (5): 649-678.
[56] Durham PL, Russo A. New insights into the molecular actions of serotonergic antimigraine drugs[J]. Pharmacol Therapeutics, 2002, 94 (1-2): 77-92.
[57] 王洪欣,孙远标,朱士文等.降钙素基因相关肽与偏头痛关系的研究[J].脑与神经疾病杂志,2003,11(1):53.
[58] 肖峰,沈雪峰,杨士军等.偏头痛患者血浆内皮素和降钙素基因相关肽含量的变化与临床意义[J].神经疾病与精神卫生,2002,2(1):29-30.
[59] 李炜,邓干初,刘远珍等.针刺肝胆经穴治疗偏头痛207例临床研究[J].中医杂志,2002,43(11):824-825.
[60] 闫国平,赵晏.P物质参与痛觉调控的研究进展[J].国外医学生理、病理科学与临床分册,1996,16(3):195-197.
[61] 王宇卉,曹文辉.偏头痛的生化研究进展[J].国外医学:神经病学·神经外科学分册,1994,21(2):71—75.
[62] 刘晓萍,徐珞,于业军等.大剂量雌二醇对大鼠血浆和组织中P物质和锌离子含量的影响[J].中国高血压杂志,1995,3(1):21-22.
[63] 刘晓萍,徐珞,于业军等.雌激素诱发大鼠免疫器官退化及与P物质关系的研究[J].河南医科大学学报,1995,30(4):393-395.
[64] Olesen J, Thomsen LL, Iversen H. Nitric oxide is a key molecule in migraine and other vascular headaches[J]. TrendsPharmacolSci, 1994, 15(5): 149-153.
[65] Bellantonio P, Micieli G, Buzzi MG, et al. Haemodynamic correlates of early and delayed responses to sublingual administration of isosorbide dinitrate in migraine patients: a transcranial Doppler study[J]. Cephalalgia, 1997, 17 (3): 183-187.
[66] 连亚军,王左生,邱亚峰等.头痛患者血浆一氧化氮和降钙素基因相关肽含量测定[J].河南医科大学学报,1998,33(2):64-66.
[67] Tan DY, Zhang LZ, Zhao YT, et al. Involvement of nitric oxide in the vasodilator and depressor effect ofcalcitonin gene-related peptide[J]. Chin Med J, 1994, 107(10): 745-749.
[68] Fozard JR. The 5-hydroxytryptamine-nitric oxide connection: the key link in the initiation of migraine[J]. Arch Int Pharmacodyn Ther, 1995, 329 (1): 111-119.
[69] Imthurn B, Rosselli M, JaegerAW, et al. Differential effects of hormone-replacement therapy on endogenous nitric oxide(nitrite/nitrate) levels in postmenopausal women substituted with 1713-estradiol valerate and cyproterone acetate or medroxyprogesterone acetate[J]. J Clin EndocrinolMetab, 1997, 82(2): 388-394.
[70] 张锁龙,吴国球,凌玲等.17β-雌二醇对ox-LDL诱导内皮细胞一氧化氮生成的影响[J].中国心血管杂志,2001,6(6):313-316.