文章信息
- 葛晓晨, 师伟, 徐丽, 李彦楠, 张绪丹, 石雅馨, 李思毅
- GE Xiaochen, SHI Wei, XU Li, LI Yannan, ZHANG Xudan, SHI Yaxin, LI Siyi
- 子宫内膜损伤性疾病“异病同治”思路探究
- A probe into the idea of "simultaneous treatment of different diseases" in endometrial injury diseases
- 天津中医药, 2021, 38(6): 804-810
- Tianjin Journal of Traditional Chinese Medicine, 2021, 38(6): 804-810
- http://dx.doi.org/10.11656/j.issn.1672-1519.2021.06.27
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文章历史
- 收稿日期: 2021-04-20
2. 山东中医药大学附属医院妇科, 济南 250014;
3. 山东第一医科大学附属省立医院中医科, 济南 250021;
4. 陕西中医药大学, 咸阳 712046
子宫内膜损伤性疾病是指因子宫局部创伤感染导致内膜结构异常及其功能紊乱的一类疾病,中医方面可表现为带下病、崩漏、经期延长、不孕等。西医方面主要表现为子宫内膜炎、宫内节育器(IUD)出血副反应、瘢痕憩室等疾病。笔者从中西医角度出发,基于“异病同治”理论,探究子宫内膜损伤性疾病的共性病因病机及证治特点,具体阐述如下。
1 疾病概念子宫内膜损伤性疾病是因子宫位置、宫腔兼容性、体质等生理因素或因机械性损伤、局部创伤感染、内分泌免疫失调等病理因素导致子宫内膜局部形态创伤及功能紊乱的一类疾病。根据病因和临床表现,可将子宫内膜炎、IUD出血不良反应、瘢痕憩室等归为子宫内膜损伤性疾病。其中子宫内膜损伤后,细菌沿阴道、宫颈上行、或沿输卵管下行、或经淋巴系统到达子宫内膜致内膜结构发生炎性反应则为子宫内膜炎,临床表现为盆腔疼痛、月经异常、白带增多、痛经等[1-2],育龄妇女放置节育器后压迫改变子宫内膜形态、内膜局部生化物质及相关受体发生变化,表现为子宫内膜剥脱或修复异常则为IUD出血不良反应,临床表现为异常子宫出血[3];剖宫产术后子宫切口愈合不良或继发感染,愈合缺陷则为剖宫产瘢痕憩室(CSD),异常性子宫出血是主要临床表现[4]。
中医学尚无子宫内膜损伤性疾病这一诊断,但根据病因病机及临床症状,中医学的“癥瘕”“带下病”“崩漏”“经期延长”等均可归为子宫内膜损伤性疾病范畴,它们具有共性病因病机,以子宫异常出血、月经不调、白带异常等为主要临床表现,西医学的子宫内膜炎、瘢痕憩室、IUD出血不良反应等疾病中以血瘀、热毒、气虚为主要病机的均可参照本类疾病治疗。
2 基于“异病同治”探究子宫内膜损伤性疾病共性病因病机 2.1 子宫内膜损伤性疾病中医共性病因病机探究 2.1.1 阴虚阳搏,冲任不固《素问·阴阳别论》最早记载“崩”并提出“阴虚阳搏,谓之崩”,而“漏下”一词最先见于《金匮要略·妇人妊娠病脉证并治》。华佗《中藏经·积聚癥瘕杂虫论第十八》中“积聚癥瘕……皆五脏六腑真气失而邪气并,遂乃生焉”指出内外合邪导致带下癥瘕。《诸病源候论·妇人杂病诸候二》曰:“漏下者,由劳伤血气,冲任之脉虚损故也。”指出漏下的病机为冲任不固。《圣济总录·妇人血气门》中的“冲任之脉,所至有时。若非时而下,犹器之津泄,故名曰漏下”与《丹溪心法·崩漏》中所言“夫妇人崩中者,由脏腑伤损,冲任二脉血气俱虚故也”进一步印证了这一观点。
现代医家认为,正气亏虚、冲任不固是子宫内膜损伤性疾病的主要病因。刘瑞芬指出宫环出血关键性病因为“环卧胞宫”“金刃所伤”,总体病机是冲任不固,经血妄行,阶段性病机虚实夹杂,同时认为体质对病机也会产生影响[5]。吴书娜等指出子宫内膜炎发生的先决条件为内膜的先期受损[6],换言之,先期冲任不固,气血亏虚,发之为病。
2.1.2 瘀滞热灼,久则致虚《诸病源候论·妇人杂病诸候二》提出因瘀致崩的观点:“崩而内有瘀血,故时崩时止,淋沥不断。”医家张仲景认为带下属瘀血在少腹不去故也。《妇人大全良方·调经门》指出血不循经亦致瘀:“血崩乃经脉错乱,不循故道,淖溢妄行,一二日不止,便有结瘀之血,凝成窠臼。”同时有医家提出因热致病的观点。李东垣在《女科经纶·崩带门》中言:“女子漏下恶血,或暴崩不止,多下水浆之物。皆由饮食不节,或劳伤形体,或心气不足,致令心火乘脾,脾土受邪。”指出崩漏属火热为病也。《女科经纶·带下证》中张洁古认为“带下证,皆任脉经虚也……原其本,皆湿热结于任脉,故津液涌溢,为赤白带下”。而后也有医家提出因虚致病的思想,阴阳相维,互为其根。《校注妇人良方·调经门》中曰:“妇人月水不断,淋漓腹痛,或因劳损气血而伤冲任,或因经行而合阴阳,以致外邪客于胞内,滞于血海故也。”明代医家张景岳在《景岳全书·瘕类》指出“妇人久癥宿痞,脾肾必亏,邪正相搏,牢固不动,气联子脏则不孕,气联冲任则月水不通”;《女科经纶·崩带门》中“赵养葵曰:阳不足,则降者胜,血出下窍。慎斋按:阴血大下,阳不能维固,当以无形之气,生有形之血也。”
现代医家认为瘀、热、虚也是导致疾病发生的重要原因,邪气瘀则不通,久积成热,日久而虚。章勤、徐娟共同指出瘢痕憩室内外因夹杂,外因为金刃损伤冲任,内因为亡血伤津、气血虚弱,瘀、热、虚为其关键病机[7-8]。瞿晓竹[9]认为子宫内膜炎的病机为正气亏损、气血瘀滞、湿热瘀结。现代研究表明[10-13]宫腔操作或手术不当会致使冲任胞宫损伤,肾精不足,有形之血骤伤,血海亏损。
综上,可以看出,子宫内膜损伤性疾病的病位主要在冲任、胞宫,涉及肾、肝、脾三脏,主要病因为金刃损伤冲任胞宫,共性病机是瘀、热、虚,关键性病机是血瘀,临床多见实证和虚实夹杂[14],共同表现是经血不调。前期金刃异物直接损伤胞宫脉络,经脉瘀阻,冲任不固,经血非时妄行,以实为主。后期由实转虚,累及肝脾肾三脏,瘀久化热,耗血伤气,子宫切口不能得到濡养,愈合缓慢甚则不敛,邪毒入里化热,久灼成腔,新血不得归经,则经漏不止,加之体质因素影响,冲任脉不通畅,气血不调和,脏腑功能失常[5-7]。
2.2 子宫内膜损伤性疾病的西医共性发病机制研究 2.2.1 子宫内膜的形态学改变子宫内膜的形态学改变是子宫内膜损伤性疾病发生的先决条件。子宫内膜损伤后,在内膜周期性修复过程中,纤维细胞被过度活化,会在子宫内膜损伤处过度积累,从而导致子宫内膜形态学的改变。吾师团队前期研究分别从二维和三维空间观察置环后子宫内膜形态[10, 15],结果显示宫环出血与血管形态和功能异常关系密切[16],置环后内膜局部表浅微血管扩张、瘀血阻滞、螺旋动脉收缩功能下降,并引起收缩功能相关结构改变,内膜剥脱异常加重出血。后期探讨宫宁颗粒对置环后大鼠模型子宫血管构筑影响[17]时,结果显示血止后SMα-action表达较前明显增加,子宫血管平滑肌细胞(VSMC)表型转化是宫环出血的原因之一,内膜周期性修复障碍是IUD出血副反应患者的病理基础[18]。同时对三七、茜草有效组分宫内缓释系统调控研究[19-22]显示:三七、茜草有效组分可能以Rho/Rock通路为靶点[23],干预子宫内膜VSMC表型转化从而防治该病的发生,进一步明确了宫环出血的机制。刘庆、陈玉清[24-26]也指出子宫内膜形态学的改变是引起子宫内膜炎的前提因素。薄乃秀[27]指出基质金属蛋白酶及其组织抑制剂在组织修复、炎症反应和肿瘤浸润转移在内膜炎中高表达[28]。多个团队[29-32]指出子宫憩室的B超形态学改变与异常子宫出血具有相关性,憩室的宽度是引起出血的重要危险因素。剖宫产子宫下段切口位置、切口缝合方式和材料、瘢痕部位内膜异位、剖宫产次数、感染等也是引起引起瘢痕憩室的高危因素。
2.2.2 免疫功能的异常免疫系统功能与健康密切相关,免疫是保证机体正常运作的重要防御机制。外界侵入性因素导致子宫内膜损伤后,受损部位免疫功能下降,促进炎症、感染的发生。刘庆通过研究中药穴位注射加CO2激光照射前后子宫内膜炎大鼠的内膜病理形态学及免疫功能[24-25]推测疗效机制之一可能为形态学或免疫功能的改善。赵红琼[33]观察发现运用中药复方制剂处理子宫内膜修复较好,指出子宫内膜的先期受损、机体抵抗力下降是子宫内膜炎发生的先决条件。
综上,子宫内膜损伤性疾病发生的先决条件为子宫内膜的形态学改变[34],受损部位免疫功能的下降大大提高了发病率。宫腔操作是引起子宫内膜形态学改变的主要因素,瘢痕憩室多形成于剖宫产术后,剖宫产切口位置不当是目前公认的原因之一。IUD出血不良反应为机械压迫,使螺旋动脉管径变细且走行迂曲,增加了阻力,血液流速减慢,影响子宫内膜及血管的发育而致异常的子宫内膜出血[35]。
3 中西医结合治疗进展目前临床治疗子宫内膜损伤类疾病,临床西药治疗多采用口服避孕药与中成药或抗生素联用。研究[36, 37]指出子宫内膜中部分炎性介导因子增多及免疫因子减少是子宫内膜发生炎症病变的病理基础。对于子宫内膜炎的治疗,临床多采用甲孕酮联合二联抗生素或抗生素联合妇科千金片。对于IUD出血副反应,首先应排除IUD异常改变,临床多口服避孕药(去氧孕烯炔雌醇片)、吲哚美辛、吲哚美辛与中成药合用、氨甲苯酸联合维生素E或行取环术。常用中成药有宫宁颗粒、妇科养荣胶囊等。上环后子宫异常出血患者采取的炔孕酮治疗[38]。研究表明[15, 17]宫宁颗粒能抑制纤维蛋白溶解,活血祛瘀,中西药物结合方案可增强疗效;对于瘢痕憩室,中西医结合治疗研究尚少,多采取手术治疗,以微创为主,临床对于无生育要求、症状明显及拒绝手术的患者,多采用口服短效避孕药或选择左炔诺孕酮宫内节育器治疗[39]。但避孕药不良反应较明显且具有一定的局限性,仅适用于拒绝手术且需要避孕的患者。微创手段包括宫腔镜、腹腔镜、阴式手术、开腹手术及联合术式(宫腹腔镜联合修补术)等[40],目的主要是缓解异常子宫出血及修补肌壁缺损从而减少妊娠并发症。目前对于手术方式的选择[41],多数学者主张根据患者的生育要求、病损的程度及术者操作熟练程度来进行个体化选择。
由此可见,目前子宫内膜损伤性疾病的临床中西医结合治疗方案较单一,药物治疗多以避孕药、抗生素结合中成药为主,尚无研究分类归纳该类疾病共性病因病机,进一步总结完善临床中医治疗方案,随着国家政策对中医药的不断支持,中医药治疗逐渐展现出其显著优势。本研究从这一临床需求出发,归纳子宫内膜损伤性疾病病因病机,其临床常见治疗方案总结如下。
4 以证统病,异病同治中医学讲求整体观念、因时制宜、异病同治,对于子宫内膜损伤性疾病,临床多从瘀、热、虚三方面入手,分阶段对症治疗。肝木主生,生意畅遂,木气条达,则经血温升,不至下泄。生意郁陷,木气不达,经血陷流,则病崩漏,故疏肝调经也是临床主要辅助疗法之一[42]。
4.1 治疗初期以攻为主,化瘀止血疾病初期,血瘀为关键性病机,瘀血停留胞宫,宫室不宁致血不循经,子宫出血为主要表现。《血证论·吐血》言:“凡治血者,必先以祛瘀为要。”不论是宫环出血、瘢痕憩室还是子宫内膜炎,临床均有月经量增多甚至崩漏的症状出现,治疗初期多止血,以塞其流,同时应注意止血不留瘀[43-45]。刘瑞芬[46]自拟宫宁方止血调经,海派陈氏妇科善以“黑蒲黄散”祛瘀生新[47],刘瑞霞[48]以桃红四物汤为底加减化裁活血祛瘀,章勤[6]主以加味失笑散攻瘀畅流,多数临床研究[49-52]主张采用清热活血化瘀法,传统方剂有慢盆消炎方、红藤败酱散、当归芍药汤等。前期治法总体以化瘀止血为主,多采用三七、茜草、红藤、芍药、桃仁、红花等活血止血药物,常用中药汤剂有桃红四物汤、桂枝茯苓汤、血府逐瘀汤、大黄牡丹汤、失笑散等,常用中成药有大黄蛰虫胶囊、桂枝茯苓丸、血府逐瘀胶囊、散结镇痛胶囊等。
4.2 中后期以补为主,补肾健脾,兼以疏肝疾病中后期,以虚为主,正所谓“邪之所凑,其气必虚”,临床治疗多从补肾养阴入手,刘瑞霞[48]后期以胶艾汤化裁结合五运六气健脾补气养血,章勤[6]主以固冲汤加减标本双固,傅萍[53-54]主张“阴中求阳”,善用炒黄芪、炒党参补气生津。治法总体以补肾健脾为主,兼以疏肝理气,常用中药有阿胶、黄芪、党参、龟甲、鹿角胶、熟地黄、牡蛎、川芎、延胡索等,常用中药汤剂有温经汤、胶艾汤、固冲汤、补中益气汤、逍遥散、人参归脾汤、炙甘草汤等,常用中成药有艾附暖宫丸、暖宫七味丸、红花如意丸、妇科再造胶囊、参坤养血颗粒等。
5 总结及展望子宫内膜是人体躯体器官中唯一典型的具有周期性、整体性的自我更新再生的局部组织。子宫内膜的局部形态损伤是子宫内膜损伤性疾病的病理基础[55-56],子宫内膜损伤加之炎性改变引发子宫内膜炎,置环后金刃损伤胞宫易引发出血副反应,剖宫产术后子宫切口愈合不良合并感染造成瘢痕憩室[57-59]。综上对3种疾病的论述,发现其中西医病因病机方面均具有共性,子宫内膜损伤性疾病的中医关键性病因是金刃损伤,在西医角度,为子宫内膜的形态学改变,是子宫内膜损伤性疾病的病理基础。共性病机为瘀、热、虚,疾病特点具有阶段性,以实为主、以虚为主、虚实夹杂分别体现疾病发展的不同时期。临床多从瘀、热、虚3方面入手,治疗初期以攻为主,中后期攻补兼施。妇产科学由于超声、妇科检查及局部手术诊治的常规应用,子宫内膜病变具有高发病、高复发的特点,是治疗周期长、单一方案难以应对的复杂病种[60-62]。中医病因病机的抽象概念化与西医生理病理通路的复杂性,也对明确该类病种的共性发病机制和干预防治增加了难度。
中医学的通因通用、异病同治、因时制宜思想贯穿子宫内膜损伤性疾病的治疗过程,本篇以疾病共性病因病机为参考,指导临床治疗,突破了病种诊治的局限性,为中西医的疾病诊治提供了新思路,从子宫内膜损伤性疾病分类的角度出发,异病同治,有利于中西医认识互参,促进优势互补,提供疾病防治新思路。
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2. Department of Gynecology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China;
3. Chinese Medicine Department, Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China;
4. Shaanxi University of Chinese Medicine, Xianyang 712046, China