摘要
目的:探讨宫宁颗粒调控IUD(宫内节育器)出血副反应子宫内膜剥脱/修复相关机制。方法:在临床试验研究中,对IUD出血副反应患者进行宫宁颗粒和消炎痛两种药物干预,并设未放置宫内节育器的空白对照组,在观察疗效的同时,采用宫腔镜对子宫内膜的IUD压迫区、移行区和远器区进行观察并定点取材,比较各区治疗前后及与空白对照组在常规组织形态学的变化,并检测ER(雌激素受体)及PR(孕激素受体)的表达情况。结果:宫宁颗粒的临床疗效、中医证候改善率明显优于消炎痛组(P<0.05)。形态学观察表明,IUD出血副反应患者子宫内膜存在明显的病理学组织损伤,其组织损伤程度与距离IUD的远近成反比,距离越远,损伤越轻,且表现为明显的内膜发育不同步和剥脱/修复障碍;较之正常对照组,ER、PR表达在子宫内膜压迫区、移行区明显降低,在远器区明显升高(P<0.05),且内膜不同部位的各项指标表达均不一致(P<0.05或P<0.01)。IUD出血副反应患者治愈或好转后,内膜病理损伤明显减轻,内膜剥脱修复障碍消失或减轻;内膜ER、PR的表达有上升的趋势,且表达不同步现象消失或好转。在改善内膜病理损伤和内膜ER、PR表达不同步方面,宫宁颗粒明显优于消炎痛(P<0.05)。
结论:IUD出血副反应患者明显存在子宫内膜周期性剥脱/修复的障碍,宫宁颗粒通过减轻子宫内膜的组织形态学损伤,调整和恢复内膜ER及PR的表达,从而纠正IUD出血副反应的子宫内膜剥脱/修复紊乱,且宫宁颗粒的临床疗效、中医证候疗效和对子宫内膜剥脱/修复紊乱相关指标的改善明显优于消炎痛。
Objective: To discuss the endometria’s peeling and recovery mechanism concerning control of the side reaction of bleeding after IUD placement by Gongning granula.
Method: In the clinical experimental investigation, Gongning granula and Indometacin are used for the patients suffered by side reaction of bleeding, and it is assumed that without IUD blank group is placed; while observing herapeutic effect,uterine cavity is also adopted to observe pressure area,transition area and distant area, and sample is taken at a certain point. changes of different parts prior to and after the treatment are compared, those parts and the blank control groups are also compared in terms of conventional organization morphology, and the empress of ER and PR are examined.
Results: The clinical curative effect and the improvement rate of traditional Chinese medicine of Gongning granula obviously better than Indometacin group(P<0.05)。The observation of morphology indicate that, the endometria’s of the patients that the adverse reaction of bleeding after IUD placement exist obviously patho-damagement in histological anatomy, it’s degree of the patho-damagement inverse proported with the distance to IUD, the farther distance the slighter pain, as well it appears the obviously derangement of endometria’s and the disturbance of stripping or recovery. Compare to normal control. After the patients that the adverse reaction of bleeding after IUD placement healing well or improved, the patho-damagement of the endometria’s obviously relieved, the disturbance of stripping or recovery endometria’s vanished or lightened; although the empress of ER and PR appears the tendency of height or degrade,but out of synchronia vanished or improved. In the directions to the improvement endometria’s patho-damagement and the empress of ER, PR Gongning granula obviously better than Indometacin(P<0.05).
Conclusion: The patients who have IUD bleeding side reaction have an obvious hindrance of endometria peeling and recovery periodically, Gongning granula adjusts and recovers the delivery of endometrium ER and PR the abnormal construction of uterus vessels, by relieving the impair of endometrium tectology, so as to adjust peeling and recovery endometrium foul-up of IUD bleeding side reaction. Gongning granula's clinical effect、effect on traditional medical syndrome and improvement of relative indexes of endometrium exfoliating/repairing foul-up excels to Indometacin obviously.
引文
[1] 张玉珍.中医妇科学.第 1 版.北京:中国中医药出版社,2000;350-351.
[2] 曹泽毅.中华妇产科学.第 1 版.北京:人民卫生出版社,2000;2407-2412.
[3] 杜天竹,李明,罗新,等.雌二醇皮贴片防治 GyneFixIUD 早期出血副反应的疗效及机理初探.中国优生与遗传杂志,2003;11(4):106.
[4] 吴兆利.针刺对置 IUD 导致子宫出血者血浆 PG 的影响.辽宁中医杂志,2001;28(3):173.
[5] 赵智,尹红梅,刘海防.针灸治疗放置 IUD 子宫异常出血 60 例疗效观察.齐齐哈尔医学院学报,2003;24(1):41.
[6] 曹泽毅.中华妇产科学.第 1 版.北京:人民卫生出版社,2000;2388.
[7] 雷磊,尤昭玲.环血宁汤对置带铜宫内节育器家兔 NO 含量影响的实验研究.湖南中医学院学报,2001;21(3):11-13.
[8] Caser ML,MacDonald PC.The endothelin-parathyroid protein vasoactive:modulation by growth factor-β.Hum Reprod,1996;11:62~82.
[9] Strauss JF,Gurpide E.The endometrium:regulation and dysfunction.In Yen & Jaffe ed:“Reproductive Endocrinology”.3rd ed.Philadelphia:Saunders WB Co,1991;314~319.
[10] Kawano H,Motoyama T,KuglyanaK,et al.Gender difference in improvement of endothelium dependent vasodilation after restrogen supplementation.J Am Coll Cardiol,1997;30:914.
[11] Toyoski M,Jeffrey R,Horowitz BS,et al.Vascular endothelial growth faxtor/Vasculat permeability factor enhances vascular permeability via nitric oxide and prostacyclin.Circulation,1998;97:99-107.
[12] Sheppard B L,Phil D.Endometrial morphological changes in IUD users:review.Contraception,1987;36:1.
[13] 曹泽毅.中华妇产科学.第 1 版.北京:人民卫生出版社,2000;2407-2408.
[14] 董白桦,侯桂华,张友忠,等.长期放置宫内避孕器对子宫微环境的影响及其机理的研究.中华医学杂志,2003;83(10):823.
[15] 叶联顺,计垣,李红,等.放置含铜宫形器、TCU220C 和圆形宫内节育器后人子宫内膜形态的比较.生殖医学杂志,1995;4(2):100-102.
[16] 曹泽毅.中华妇产科学.第 1 版.北京:人民卫生出版社,2000;2391.
[17] 王桂敏,郑淑蓉.甾体激素与子宫内膜出血.生殖与避孕,1996,16(4):248-250.
[18] 刘昌官,李恕香,刘晓瑷,等.消炎痛宫内节育器对大鼠和兔子宫内膜影响的形态学观察.生殖医学杂志,1998;7(2):80.
[19] 潘俊峰,余玉琳,陈桂英,等.宫内节育器致异常出血子宫内膜止血反应的形态学改变.中华妇产科杂志,1995;30(9):526-527.
[20] 刘志成,陈湫波,倪秀生.放置γCuI 和 TCu220C 宫内节育器前后子宫内膜螺旋动脉形态计量学研究,1998;33(4):232.
[21] 黄丽丽,陈凌钧,陈湫波,等.放置宫内节育器后子宫内膜螺旋动脉的三维空间形态.中华妇产科杂志,1996;31(9):523-524.
[22] 曹泽毅.中华妇产科学.第 1 版.北京:人民卫生出版社,2000;2394-2398.
[23] Salmi A,Pakarinen P,Peltola AM,et al.The effect of intrauterine levonorgestrel use on the expressionof c-JUN,oestrogen receptor,progesterone receptors and Ki-67 in human endometrium.Mol Hum Reprod,1998;4:1110-1115.
[24] 刘爱华.对放置宫内节育器后经期延长 30 例的治疗体会.上海中医药杂志,1992;(11):19.
[25] 刘瑞芬.中医治疗宫内节育器引起异常子宫出血近况.山东中医杂志,1995;19(3):215-216.
[26] 李秀霞.中医辨证分型治疗宫内放置节育器后并发症 54 例.现代中西医结合杂志,2003;12(20):2187-2188.
[27] 李莉.清热化瘀宁坤汤治放环后月经异常 100 例.河南中医,2002;22(4):v 42.
[28] 汤艳秋.龟鹿固冲汤治疗宫内节育器放置后月经失调 200 例.黑龙江中医药,2002;(1):32.
[29] 朱颖,李军.安环止血汤治疗宫内节育器致异常出血.中国中医急症,2002;11(1):23.
[30] 陈文静,沈继云,周洁玲,等.串铜 394 和 TCu 2 2 0C 宫内节育器对子宫内膜形态学影响的初步观察.同济医科大学学报,1997;26(5):396.
[31] 韩向阳,吴振铎.TCu220C 宫内节育器放置 10 年以上子宫内膜形态学研究 哈尔滨医科大学学报,1995;29(4):300.
[32] LaIl TM,Afandi B,Rogers PA.The efects of levonorgestrel implants on vascular endothelial growth factor expression in the endometrium.MolHum Reprod,1999;5(1):57~63.
[33] Greb RR,Heikinheimo,Williams RF,et a1.Vascular end0thelial growth factor in primate endometrium is regulated by oestrogen-receptorand progesterone—receptor ligands in vivo.Hum Reprod,1997;12(6):1289~1297.
[34] 张华,孙海梅,周齐.ER、PR、VEGF 及其受体在宫内节育器引起子宫异常出血中作用的研究.解剖学报,2004;35(4):431-432.
[1] 张玉珍.中医妇科学.第1版.北京:中国中医药出版社,2002.350-351.
[2] 尤昭玲,王若光.宫内节育器引起异常子宫出血中医治疗述评.湖南中医药报,1998;4(3):10～11.
[2] 戴德英主编.现代中医药应用与研究大系.第7卷.妇科,上海:上海中医药出版社. 1995;280～295.
[3] 陈钢,等.柴胡止血液对置铜IUD 家兔宫腔洗液PGI2和TXB2 含量的影响.中国计划生育学杂志,1998;(7):297.
[4] 赖新玉,贾钰华,徐祥英,等.葆妇欣颗粒剂止血机理分析.中国计划生育学杂志,1998;(11):510～519.
[5] 杨正望等.妇科千金片治疗上环后经期延长61 例对比观察.湖南中医杂志,1998 ;(4):39.
[6] 尤昭玲,佘定国,徐祥英,等.葆妇欣颗粒剂止血机理分析.中国计划生育学杂志,1998;(11):510～519.
[7] 付灵梅,尤昭玲,李军.益气化瘀法对置带铜宫内节育器家兔子宫内膜形态学的影响.湖南中医学院学报,2000;20(2):1～2.
[8] 雷磊,孟延兵,尤昭玲.中医药防治IUD出血副反应的思路与方法.湖南中医药导报,2001;7(3):101
[9] 彭新君,雷磊,徐丽霞,尤昭玲.锌- 金属硫蛋白防治带铜宫内节育器出血副反应的机理探讨.湖南中医学院学报.2001;21(4):33
[10] 孟延兵,雷磊,尤昭玲.论“胞环出血”.湖南中医药导报.2001;7(1):5
[11] 郑兴龙,罗丽兰.使用IUD后月经过多与子宫内膜和宫腔液纤溶活性改变的研究进展1国外医学计划生育分册, 1988;(3):1381
[12] 肖碧莲,高纪,马丽媛,等1月经血量测定方法[J]1中华妇产科杂志, 1980;15(3):1591
[13] 曹泽毅主编.中华妇产科[M].北京:人民卫生出版社,1999.
[14] 杜成杰,蒋宝彝,张忠有,等.带节育器妇女子宫内膜光电镜观察.临床与实验病理志,1990;6(4):237-239.
[15] 刘瑞芬,栾跃芳,李继凤. 宫宁颗粒治疗使用宫内节育器出血副反应的临床研究. 中医杂志,1998;39(5):292-294.
[16] 石红.1189例取环诊刮子宫内膜临床病理分析.中国实用妇科与产科志,1995; 11(4):217-218.
[17] 郑兴龙,罗丽兰.使用IUD后月经过多与子宫内膜和宫腔液纤溶活性改变的研究进展1国外医学?计划生育册,1988;(3): 1381
[18] Toyoaki M,Jeffrey R,Horowitz BS,et a1.Vascular endothelial growth factor/vascular permeability factor enhances vascular permeability via nitric oxide and prostacy clin.Circulation,1998;97(1):99~107.
[19] Nayak NR,Critchley HO,Slayden OD,et a1.progesterone withdrawal up regulates vascular endothelial growth factor receptor type 2 in the superficial zone stroma of the human and macaque endometrium:potential relevance to menstruation.Clin Metab,2000;85(9):3442~3452.
[20] 刘小乐,杜天竹,陈衡,等.置 Cu-IUD 有或无子宫异常出血者血管内皮生长因子的表达.广东医学院学报,2005;23(4):403-405.
[21] Nesit V, Petros J,Micanik B.Adenomyosis as a social problem.Cesk Gynekol. 1990; Dec,55(10):732～40.