消化性溃疡的中医证治规律研究及临床疗效的系统评价

【作者】 石绍顺；

【导师】 周学文；

【作者基本信息】 辽宁中医药大学 ， 中医内科学， 2011， 博士

【摘要】 目的:通过消化性溃疡临床资料的回顾性分析以总结消化性溃疡中医证候分布特点及处方用药规律,为临床和科研工作提供参考,更好的发挥中医药治疗优势;总结导师周学文教授治疗消化性溃疡的处方用药等规律,推广导师临床经验及学术思想,丰富本病的中医治疗方法;对口服中药治疗消化性溃疡的随机对照试验(RCT)进行方法学质量和临床疗效及安全性评价,客观的评价中药在消化性溃疡治疗上的优势与不足,为中医药治疗消化性溃疡提供循证医学证据。材料与方法:1.通过中国生物医学文献数据库(CBM),以“消化性溃疡”为检索词进行主题检索,选择加权、全部树、全部副主题进行扩展检索,获得文献题录,再通过中国期刊全文数据库(CNKI)、维普全文数据库(VIP)、万方等中文数据库获得文献原文。对符合要求的文献将文献类别、证型名称、病例数、所用药物等进行录入,进行计量学分析。2.将导师周学文教授治疗的115例活动期消化性溃疡患者的临床资料,进行数据录入,采用频数分析和关联规则分析的方法,初步总结本病的证候特征以及导师治疗本病的思维特点、处方用药规律等知识。3.通过收集符合标准的中药治疗消化性溃疡的临床随机对照试验,按照Cochrane系统评价员手册5.0.2版及GRADE标准对试验方法学、证据质量进行评价,对提取的相关数据进行荟萃分析(meta分析)。结果:1.消化性溃疡的中医证治规律研究共纳入1103篇原文。其中辩证论治类文献168篇,非辨证论治类文献935篇。总体用药以甘草、白芍、白芨、乌贼骨、黄芪、元胡、白术、黄连、党参、蒲公英、三七、陈皮、丹参、茯苓、柴胡、香附、半夏、枳壳、砂仁、桂枝、木香等为多见。证型名称繁杂,在168篇辨证论治文献涉及中医证型名称达128种,通过归类汇总后有脾胃虚弱证、胃热炽盛证、瘀血停滞证、肝胃气滞证、胃阴亏虚证、饮食停滞证、寒邪客胃证、湿热中阻证、痰湿阻滞证、肝脾不和证、寒热错杂证、气虚血瘀证、其他(脾虚胃热、虚寒血瘀、热瘀胃络、虚实夹杂、岀血证）等证型，经统计分析?ば陀衅⑽感槿踔(32.04%)、肝胃气滞证(24.67%)、瘀血停滞证(12.14%)、胃阴亏虚证(8.46%)、胃热炽盛证(8.18%)、湿热中阻证(5.85%)六种。处方用药脾胃虚弱证常用药物有甘草、黄芪、白术、白芍、党参、桂枝、干姜等,即以六君子汤、黄芪建中汤、理中汤等为常用方剂,可适当加用白芨、元胡、乌贼骨、瓦楞子等生肌制酸,加砂仁、香附、木香等理气,丹参、三七等活血,黄连、蒲公英等清热;肝胃气滞证常用药物有甘草、柴胡、白芍、香附、枳壳、陈皮、乌贼骨、元胡等,即以柴胡疏肝散、金铃子散等为常用方剂,配合丹参、三七活血,黄连、蒲公英、黄芩等清热,黄芪、白术、党参等健脾,白芨、乌贼骨、瓦楞子等生肌制酸;瘀血停滞证常用药物有甘草、五灵脂、元胡、丹参、白芨、蒲黄、川楝子等,即以失笑散、丹参饮、金铃子散等为常用方剂,配合三七、赤芍、桃仁、川芎、红花等活血化瘀,香附、乌药、陈皮等理气,黄芪、党参、白术、当归等益气养血,黄连、蒲公英等清热解毒;胃阴亏虚证常用药物有麦冬、甘草、沙参、白芍、石斛、白芨、黄芪、生地、玉竹等,即以益胃汤、麦门冬汤、芍药甘草汤等为常用方剂,配伍乌贼骨、瓦楞子制酸,黄芪、白术、党参、当归等补气养血;胃热炽盛证常用药物以黄连、蒲公英、栀子、丹皮、黄芩清热解毒,元胡、丹参、三七等活血,白芨、乌贼骨、瓦楞子生肌制酸。香附、枳壳、青皮等理气,黄芪、白术健脾;湿热中阻证常用药物以黄连、半夏、茯苓、黄芩、苍术、蒲公英、厚朴、栀子、薏苡仁等清热利湿,白芨、乌贼骨、瓦楞子等生肌制酸,党参、白术、黄芪等健脾。2.周学文教授治疗消化性溃疡的经验与数据挖掘纳入115例消化性溃疡患者,临床症状以胃脘疼痛、痞满、反酸、口干、嗳气、烧心、纳呆、恶心、口苦、呕吐为主,其他症状还有寐差、大便干、腹痛、黑便、打嗝、烦躁易怒、大便溏、口粘等。舌质以舌红、红绛为多见,舌苔以黄腻苔、积粉苔、腐苔、薄黄苔多见,脉象以弦脉、弦滑脉及弦数脉为多见,胃镜下溃疡周围粘膜可见充血水肿。证型分布胃脘毒热证最为多(62%),其次为肝胃气滞证(15%)、脾胃虚弱证(11%),再次为瘀血停滞证、胃阴不足证,而脾胃虚寒最为少见(1%)。治疗上以清热解毒,敛疮生肌,配合补脾益气、疏肝、理气(行气)、活血等。治疗处方147首,用药91味,常用药物有黄芪、黄连、白芨、浙贝母、甘草、柴胡、苦参、蒲公英、乌贼骨、元胡、三七、青皮、苏叶、金铃子、煅瓦楞、白豆蔻、丹参、砂仁等。常用配伍有黄连和黄芪、金铃子和元胡、浙贝母和乌贼骨等等。3.中药治疗消化性溃疡疗效及安全性的系统评价纳入13篇随机对照试验(RCT),包括3036例患者,样本含量从72到494不等,所有研究方法学质量:①有3个研究描述了隐蔽分组情况,②有2个研究提及研究过程中存在病例的剔除、失访及退出,③所有研究均未进行意向性分析,④4个研究描述了不良反应的发生,⑤8个研究所用试验药物为研究者经验方或其院内制剂,⑥所有研究未进行临床试验注册;证据质量分析:按GRADE标准所有研究评价结果均为低质量或极低质量证据。Meta分析结果显示:所选RCT中部分中药治疗消化性溃疡的胃镜治愈率、中医症候疗效的有效率优于雷尼替丁(P=0.002,P=0.0004)。半年及一年溃疡的复发率低于雷尼替丁(P=0.004,P<0.0001);所选RCT中部分中药治疗消化性溃疡的胃镜有效率、中医症候疗效的治愈率与雷尼替丁没有明显差异(P=0.56,P=0.08);所选RCT中部分中药对HP阳性的消化性溃疡患者HP阴转率与雷尼替丁没有明显差异(P=0.10),与雷尼替丁+阿莫西林+甲硝唑无差异[RR=1.60(95%CI:0.94,2.73],与奥美拉唑+阿莫西林+替硝唑有差异RR=0.08(95%CI:0.03,0.23]。结论:1.消化性溃疡的中医证治规律研究消化性溃疡的常见证型有脾胃虚弱证、肝胃气滞证、瘀血停滞证、胃阴亏虚证、胃热炽盛证、湿热中阻证等。脾胃虚弱是消化性溃疡发病的主要机制,也是溃疡复发的主要原因。治疗上脾胃虚弱证以六君子汤、黄芪建中汤、理中汤等为常用方剂,可适当加用生肌制酸药,配伍理气活血、清热解毒之品;肝胃气滞证以柴胡疏肝散、金铃子散等为常用方剂,配合活血清热解毒,及健脾、生肌制酸之品;瘀血停滞证以失笑散、丹参饮、金铃子散等为常用方剂,配伍三七、赤芍、桃仁、川芎、红花等活血化瘀,配伍理气健脾益气养血、清热解毒之品;胃阴亏虚证以益胃汤、麦门冬汤、芍药甘草汤等为常用方剂,配伍制酸、健脾补气养血之品;胃热炽盛证以黄连、蒲公英、栀子、丹皮、黄芩清热解毒,配伍理气活血及生肌制酸、健脾之品;湿热中阻证常用药物以黄连、半夏、茯苓、黄芩、苍术、蒲公英厚朴、栀子、薏苡仁等清热利湿,配伍生肌制酸、健脾益气之品。无论哪一证型的治疗用药都或多或少的有黄芪、白术等健脾益气类药物及白芨、乌贼骨、瓦楞子等生肌制酸药物以提高疗效。2.周学文教授治疗消化性溃疡的经验与数据挖掘导师周学文教授针对消化性溃疡的临床特征及胃镜改变提出“胃痈”病名,创新“毒热”学说,认为其病机以脾胃虚弱为本,毒热蕴结为标,久病入络,气血瘀滞为变。提出“以痈论治”的治疗思想,将“消”、“托”、“补”三法引入治疗,以清热解毒、消痈生肌为主要治法,确立主体方药消痈溃得康,临证随机调节,注重药物的配伍应用,强调尤要处理好肝脾、胆胃关系,注意调节气机升降,适当使用活血化瘀、滋养胃阴及调脾养心之品,同时可以针对幽门螺杆菌(hp)用药及提高疗效。强调观看舌象以明疾病的进退预后,药物剂量不宜过大,重视煎服法及饮食调摄等。3.中药治疗消化性溃疡疗效及安全性的系统评价部分中药治疗消化性溃疡的胃镜治愈率、中医症候疗效的有效率优于雷尼替丁,半年及一年溃疡的复发率低于雷尼替丁,部分中药治疗消化性溃疡的胃镜有效率、中医症候疗效的治愈率与雷尼替丁没有明显差异,部分中药对HP阳性的消化性溃疡患者HP阴转率与雷尼替丁没有明显差异,与三联疗法(雷尼替丁+阿莫西林+甲硝唑)无差异,而与(奥美拉唑+阿莫西林+替硝唑)有差异。但由于所有研究的方法学质量与证据质量较低,对本研究的结果需谨慎对待,今后应更加规范科研设计,延长随访时间,注重药物安全性与不良反应,并按照中医药随机对照试验报告统一规范(CONSORT for TCM)中推荐的流程和项目报告RCT。更多还原

【Abstract】 Purpose:In order to provide reference to clinical experience and scientific research, and reflect advantages of Traditional Chinese Medicine (TCM) in peptic ulcer (PU), this article conclude the differentiation-prescription rules of PU by a retrospective analysis of clinical data of PU;In order to spread clinical experience and academic thoughts of professor Zhou Xuewen,through summarized the rules of prescriptions to treat PU;analyzed the methodology for quality , curative effect and clinical security about literature of oral traditional chinese medicine randomized controlled trials (RCT) in PU,and valuate objectively the advantages and disadvantages of TCM in the treatment of peptic ulcer, so as to provide evidence of evidence-based medicine(EBM)Material and method:1.To get the catalog of the documents through China biomedical(CBM) literature database by using peptic ulcer (PU)as key words for subject access select weighted, all trees, all sub-themes to extend search. Then access to bibliography by the Chinese Academic Journal (CNKI) ,VIP Full-text databases,( VIP), WANFANG Database to obtain the original documents in Chinese,Have a metrological analysis with the literature that meet the requirements of document class name of syndrome the number of cases drugs used2. Entering the clinical data of the 115 example of the active stage peptic ulcer patients. Concluded the character of the disease symptom and the knowledge of the treatment and laws of using drugs by using the methods of frequency analysis and the associated rules method of analysis.3.Through collecting standard chinese medicine treatment of peptic ulcer R randomized controlled trials. In accordance with the Handbook 5.0.2 System Evaluation GRADE standards .The methodology of the literature Quality of Literature Evaluation .The extracted meta-analysis of relevant data. Results:1. The research of PU through TCM treatmentIncorporate 1103 pieces of original artial, there were 168 pieces artia were about treatment according to syndrome differentiation and 935 were not, The drugs are more common in Licorice, white peony root, Baiji, cuttlefish bone, astragalus, Yuan Hu, Bai Zhu, berberine, Codonopsis, Dandelion, Panax, dried tangerine peel, red sage root, Poria, Bupleurum, Cyperus rotundus, Pinellia, Citrus aurantium, Amomum, Guizhi , Mu-xaing, etc . The names of the syndrome were miscellaneous, there were 128 types of name among in 168 pieces text that were about treatment according to syndrome differentiation. Through the classified summary there were spleen-stomach deficiency, certificates stomach heat flaming, blood stasis stagnation card, liver and stomach-Qi stagnation, stomach-yin deficiency, diet stagnation card, Han-xie off stomach card, hot and humid in the resistance card, phlegm block card, disharmony between liver and spleeen, cold and heat mixed card, with Qi-deficiency and blood -stasis , the others (spleen-stomach heat, cold and blood stasis, heat stasis stomac-luo, the actual situation inclusions, Bleeding), and other syndromes, and there were six types of syndrome were in common: spleen-stomach deficiency (32.04%), liver and stomach qi stagnation (24.67%), blood stasis stagnation card (12.14%), stomach-yin deficiency syndrome (8.46%), stomach heat flaming card (8.18%), hot and humid in the retention syndrome (5.85%).The prescription to treat the syndrome of spleen-stomach deficiency is Licorice, Astragalus, Atractylodes, white peony root, Codonopsis, cassia twig, dry ginger, etc., which is so called Liujunzi Tang, Huangqi-Jianzhong Tang, Li Zhong Tang and can be properly added with Baiji, Yuan Hu, cuttlefish bone, and other myogenic corrugated sub-acid, add villosum, Cyperus rotundus,mu-xiang and other regulating-qi drugs, Salvia, and notoginseng, berberine, dandelion and other heat; The prescription to treat the syndrome of liver and stomach qi stagnation is Licorice, Bupleurum, white peony root, Cyperus rotundus, Citrus aurantium, Citrus, cuttlefish bone, Yuan Hu, etc., which is so called ChaiHuShuGanSan, Jin Ling Zi Powder as the popular prescription, with panax blood Salvia, Scutellaria, etc. Coptis dandelion Heat, Astragalus, Atractylodes, Codonopsis other spleen, Baiji, cuttlefish bone, corrugated sub-acid and other myogenic; The prescription to treat the syndrome of blood stasis stagnation card is Licorice, Wulingzhi, Yuan Hu, SM, Baiji, Puhuang, Toosendan so, that Shixiaosan, Salvia drink, Jin Ling Zi Powder as the commonly used prescriptions. With notoginseng, red peony root, peach kernel, Chuanxiong, safflower and other blood circulation, Cyperus rotundus, aggregata, dried tangerine peel, etc. qi, Astragalus, Codonopsis, Atractylodes, Angelica and other nourishing Qi, berberine, and dandelion to clearing away heat and toxic material; The prescription to treat the syndrome of stomach yin deficiency is Radix, licorice root, Radix, white peony root, Dendrobium, Baiji, astragalus, habitat, Polygonatum and so on. That is, Yiwei Tang, wheat Asp soup, such as the commonly used SGD prescription, compatibility cuttlefish bone, corrugated sub-acid, Astragalus, Atractylodes, Codonopsis, angelica and other nourishing qi; The prescription to treat the syndrome of stomach heat flaming card is Berberine, dandelion, gardenia, peony tree bark, skullcap Qingrejiedu, Yuan Hu, Salvia, and notoginseng blood, Baiji, cuttlefish bone, corrugated sub-myogenic acid. Cyperus rotundus, Citrus aurantium, blue, etc. qi, Astragalus, Atractylodes spleen; The prescription to treat the syndrome of hot and humid in the retention is Coptis, Pinellia, Poria, skullcap, herb, dandelion Magnolia, gardenia, Coix seed and other heat dampness, Baiji cuttlefish bone, corrugated sub-acid and other myogenic, Codonopsis, Atractylodes, Astragalus spleen2. Professor Zhou Xuewen experience in treatment of peptic ulcer and Data MiningThe main clinical syndromes of the 115 PU patients are Epigastric pain, fullness, acid regurgitation, dry mouth, belching, heartburn, poor appetite, nausea, mouth pain, vomiting and the other syndromes are poor sleep, dry stool, abdominal pain, black stools, hiccups, irritability, loose stools, mouth stick, etc. Tongue to tongue is red, red purple is more common, tongue with yellow greasy fur product powder coating, corrosion coating, thin yellow fur common, pulse to pulse string, string taut slippery pulse and the pulse is more common, Endoscopic mucosal visible edema around the ulcer; the distribution stomach syndrome Abdominal most toxic heat syndrome and more (62%), followed by the syndrome of liver and stomach qi stagnation (15%), spleen and stomach deficiency card (11%), again blood stasis stagnation card, certificate of stomach yin deficiency, and the most rare spleen and stomach deficiency with cold (1%). Detoxification treatment to heat-based, with invigoratings Spleen Qi, myogenic convergence sores, su-gan, regulate qi (qi), blood circulation and so on. 147 treatment regimen, medication 91 flavor, commonly used drugs are Astragalus, Coptis, Baiji, Zhejiang Fritillaria, licorice root, Bupleurum, Sophora, dandelion, cuttlefish bone, Yuan Hu, Panax, blue, sage, golden bell son Duan corrugated, white cardamom, Salvia, Amomum. Compatibility with Coptis and Astragalus Common, Son, and Jin Ling Yuan Hu, and cuttlefish bone Fritillaria.3. The system evaluation of the treatment to PU by using TCMIncluded 13 randomized controlled trials (RCT), including 3036 cases of patients, sample size ranged from 72 to 494,the quality of all research methodological:①There are 3 case studies described concealment;②There are two studies have addressed the existence of cases during the study excluded lost, and exit,③all studies were not intentional analysis,④4 studies described the incidence of adverse reactions,⑤8 research institutes researchers with experience in testing drugs for the hospital or its agents,⑥study did not conduct clinical trials of all registered. The Quality of evidence: Evaluation of all research results are evidence of low quality or low quality. Meta analysis showed: endoscopic treatment of peptic ulcer cure and efficacy of traditional Chinese medicine effective symptom by some traditional Chinese medicine is better than ranitidine(P=0.002,P=0.0004), six months and one year recurrence rate of ulcers than ranitidine(P=0.004,P<0.0001);endoscopic treatment of peptic ulcer efficacy and cure of traditional Chinese medicine effective symptom by some traditional Chinese medicine as to as ranitidine(P=0.56,P=0.08);and HP conversion rate of HP-positive peptic ulcer patients did not differ significantly ranitidine(P=0.10),and not differ significantly ranitidine+ Amoxicillin + metronidazole [RR=1.60(95%CI:0.94,2.73],and differ significantly Omeprazole+Amoxicillin + tinidazole,RR=0.08(95%CI:0.03,0.23].Conclusion:1. The research of PU through TCM treatmentThe common syndrome of PU are: spleen and stomach deficiency, liver and stomach Qi stagnation, blood stasis stagnation card, stomach yin deficiency syndrome, stomach heat flaming card, hot and humid in the resistance card. spleen and stomach deficiency is the main mechanism for peptic ulcer, and for ulcer recurrence. Treatment of spleen and stomach deficiency card to Liujunzi Tang, Astragalus Decoction, the rationale for the commonly used prescriptions in the Tang may be appropriate to increase myogenic acid drug use, compatibility qi and blood circulation, detoxification of the goods; liver and stomach Qi stagnation to Bupleurum Liver Powder, Jin Ling Zi Powder as the commonly used formulas, with the blood detoxification, and spleen, tissue regeneration acid of the goods; stasis stagnation card to Shixiaosan, Salvia drink, Jin Ling Zi Powder as the common prescription, compatibility Notoginseng, red peony root, peach kernel, Chuanxiong, safflower and other blood circulation, spleen qi Qi and blood compatibility, detoxification of chemicals; stomach yin deficiency syndrome in Yiwei Tang, wheat Asp soup, peony and licorice soup For commonly used prescription, compatibility acid, spleen qi nourishing of the goods; stomach heat flaming card to berberine, dandelion, gardenia, peony tree bark, skullcap Qingrejiedu, compatibility qi and blood circulation and tissue regeneration acid, the spleen of the goods; Heat retention syndrome commonly used in drugs to berberine, Pinellia, Poria, skullcap, herb, dandelion, magnolia, gardenia, Coix seed and other heat and dampness, compatibility myogenic acid, spleen Qi of the product. No matter what type of treatment cards are more or less medication Astragalus, Atractylodes drugs such as spleen Qi and Baiji, cuttlefish bone, corrugated sub-acid drugs such as tissue regeneration to improve the efficacy. 2. Professor Zhou Xuewen experience in treatment of peptic ulcer and Data MiningProfessor Zhou Xuewen instructors for the clinical characteristics of peptic ulcer and endoscopic changes to the "stomach carbuncle" disease name, and innovation "toxic heat”theory that the pathogenesis of the spleen and stomach-oriented, heat Accumulation as the standard drug, chronic illness into the network, Blood stasis to change. That "the carbuncle on the administration " thought the treatment would "eliminate","care","up " three methods to introduce treatment to detoxify, eliminate the main governing myogenic carbuncle law, establishing the main prescription consumer health carbuncle may collapse, Clinical randomized conditioning, pay attention to the compatibility of drug application, emphasizing in particular handle well the liver and spleen, stomach, gall bladder relationship, pay attention to adjust the air-lift, the appropriate use of blood circulation, nourish Stomach-Yin and Yang Xin of the goods transferred spleen, and can for Helicobacter pylori Pylori (hp) and improved treatment efficacy. Stressed out watching the tongue to advance and retreat of disease prognosis, drug dosage should not be too large, attention to diet ,extracting and taking drugs method.3. The system evaluation of the treatment to PU by using TCM endoscopic treatment of peptic ulcer cure and efficacy of traditionalChinese medicine effective symptom by some traditional Chinese medicine is better than ranitidine, six months and one year recurrence rate of ulcers lower than ranitidine;endoscopic treatment of peptic ulcer efficacy and cure of traditional Chinese medicine effective symptom by some traditional Chinese medicine as to as ranitidine;and HP conversion rate of HP-positive peptic ulcer patients did not differ significantly ranitidine, not differ significantly ranitidine+ Amoxicillin + metronidazole ,and differ significantly Omeprazole+Amoxicillin + tinidazole.Because all of the methodological quality and evidence of low quality, the results of this study should be cautious in the future and should be more Specifications research design, extended follow-up time, pay attention to drug safety and adverse reactions, and in accordance with the medical report of randomized controlled trials of standardized (CONSORT for TCM) in the recommended process and project reporting RCT.更多还原