功能性便秘（气虚肠燥证）中医治疗方案及疗效评价研究
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摘要
功能性便秘(Functional Constipation,FC)是一种较为常见的功能性胃肠病,该病发病率高,我国慢性便秘的发病率约为6.07%,欧洲和大洋洲则高达19.8%。长期便秘对人体生理、心理造成不利影响,严重影响人们的生活质量,目前西医治疗本病存在易耐药、易复发、易致不良反应等诸多不足。中医药治疗本病缺乏高质量的临床试验,尚未形成规范的诊疗策略。我们通过对中医典籍及现代研究的整理分析,在总结既往经验的基础上,提出益气润肠法治疗气虚肠燥型功能性便秘的治疗方案,以“重建排便规律、治愈便秘”为指导思想,借助“中国中医科学院中医治疗有特色和优势病种项目临床研究课题”这一研究平台,通过临床病例观察,验证该方案治疗本病的疗效和安全性,以期总结出体现中医药理论和临床特色优势的功能性便秘中医治疗方案。本研究主要有三个部分组成：第一部分是功能性便秘的文献综述部分,分别为“中医诊治便秘的古籍整理”和“功能性便秘西医研究现状”两个方面；第二部分是系统评价与中医药,首先介绍了在中医药研究领域引入系统评价方法的重要性,其次详细介绍了“中药治疗功能性便秘随机对照试验的系统评价和Meta分析”；第三部分是益气润肠方治疗(气虚肠燥)功能性便秘的疗效评价。
理论研究：
中医古籍中有关便秘论述的整理：对秦汉至明清有代表性的中医古籍中对便秘的论述进行了系统梳理,从源及流,旁及各家,分五个部分。第一部分重点介绍《黄帝内经》和《诸病源侯论》中有关便秘生理病理及病因学的相关论述；第二部分,重点介绍《伤寒论》和《金匮要略》两书对便秘的论治特色；第三部分,主要介绍温病代表作《温病条辨》和《瘟疫论》治疗便秘的特点；第四部分,分别介绍刘完素、李东垣、张子和、朱丹溪等四位金元医家对便秘的论治；第五部分,主要介绍明清时期一些有代表性的医家对便秘的论治经验。
西医研究现状：从流行病学特点(发病率、病因及危险因素研究、卫生经济学、医疗负担等)、诊断标准、疾病分类、诊查手段、治疗措施、存在问题等方面,全面介绍了目前国内外对功能性便秘的研究现状。
系统评价：
随着循证医学的发展,应用系统评价方法对中医药疗效及安全性进行评价显得必要和迫切,目前国内外尚无对中医药治疗功能性便秘的系统评价。本研究旨在系统评价中药治疗功能性便秘的疗效及安全性。以国际Cochrane协作网公布的Cohrane Handbook5.0.2系统评价原则为指导,制订详细的检索策略、具体的纳入标准和评价标准,分别检索CNKI、CBM、VIP、Cochrane Library、Pubmed和EMBASE等数据库,对近20年国内外发表的中药治疗功能性便秘的随机对照试验进行系统评价和Meta分析。共纳入21个符合标准的研究,对其中6个研究的Meta分析结果提示中药治疗慢性功能性便秘的疗效优于促胃肠动力药,有效率RR及95%CI：1.18[1.12,1.25],痊愈率RR及95%CI：1.59[1.35,1.88]；与泻剂比较有效率RR及95%CI：1.18[1.10,1.27],痊愈率RR及95%CI：1.65[1.29,2.10]；中药联合促胃肠动力药与促胃肠动力药比较,有效率RR及95%CI：1.21[1.09,1.34],痊愈率RR及95%CI：1.41[1.11,1.79]。漏斗图分析提示,纳入研究存在一定的发表偏倚。有限的研究提示：中药治疗慢性功能性便秘安全有效,但因纳入研究的质量普遍不高,目前还不能得出较为可靠的结论。
临床研究：
目的：评价益气润肠方治疗气虚肠燥型功能性便秘的临床疗效及安全性。
方法：临床筛选气虚肠燥型功能性便秘受试者60例,随机分为治疗组30例和对照组30例,分别给予经验效方益气润肠汤及芪蓉润肠口服液治疗,疗程4周,随访4周,通过对通便效果、中医证候积分、结肠运输试验、安全性等指标的观察,比较两种方案对气虚肠燥型功能性便秘的治疗效果。
结果：
临床和证候学疗效：治疗组临床疗效的有效率和痊愈率(90.0%,46.7%)高于对照组(66.7%,20.0%),差异有统计学意义(P=0.04)。治疗组证候疗效的有效率和痊愈率(86.7%,46.7%)高于对照组(63.3%,16.7%),差异有统计学意义(分别为p=0.02、p=0.04)。治疗组平均起效时间26±13.9(小时),对照组37.2±30.3(小时),二者通便起效时间差异有统计学意义(P=0.027)。中药汤剂较芪蓉润肠口服液通便起效时间短。
持续稳定性疗效：疗程结束时,治疗组排便质量1级的受试者多于对照组,排便质量为3级的受试者低于对照组,二者差异均有统计学意义(分别为p=0.02、p=0.03)。两组第四周、第八周排便间隔时间均短于治疗前,差异有统计学意义(P<0.05)；治疗组第四周与第八周比较差异无统计学意义(P=0.12),对照组第四周与第八周比较差异有统计学意义(P<0.0001)。表明治疗组中药汤剂持续稳定性好。对照组复发率高于治疗组,但二者差异并无统计学意义(P=0.36),在预防复发方面治疗药物与对照药相当。
单项症状疗效：第八周随访时治疗组的排便费力症状积分与第四周比差异有统计学意义(P<0.001),对照组的排便间隔延长、排便费力、大便性状积分与第四周相比差异有统计学意义(P<0.05)。说明治疗组药物在改善排便费力方面持续稳定性差,对照药物改善排便间隔延长、排便费力、大便性状等方面持续稳定性差。疗程第四周,治疗组在排便间隔延长、排便费力、疲惫乏力、神疲懒言等症状积分值低于对照组,且差异有统计学意义(P<0.05)；疗程第八周,治疗组排便间隔延长、大便性状、疲惫乏力、神疲懒言等症状积分值低于对照组,差异有统计学意义(P<0.05)。
结肠传输试验疗效：治疗组结肠传输试验有效率高于对照组,差异有统计学意义(p=0.02),益气润肠汤剂在改善功能性便秘受试者结肠传输功能方面优于芪蓉润肠口服液。治疗组痊愈率高于对照组,二者差异无统计学意义(p=0.08)。治疗前两组24小时、48小时、72小时标志物存留数差异均无统计学意义(P>0.05)。治疗组治疗前后72小时、48小时标志物存留数差异有统计学意义(p<0.00001),24小时标记物存留数差异无统计学意义(P=0.58)。提示中药汤剂能明显改善结肠传输功能,在48、72小时时段尤为明显。对照组治疗前后24、48、72小时结肠标记物存留数差异均无统计学意义(P>0.05),提示芪蓉润肠口服液在改善结肠传输功能方面疗效不及中药汤剂。
不良反应：治疗期间对照组1例受试对象因便秘加重出现肠梗阻,退出试验；另有一例出现轻度腹泻、腹痛,未经特殊处理,自行缓解。治疗组有2例受试对象出现轻度腹痛、腹泻,减量服药后症状消失,两组均无严重不良事件发生。
结论：益气润肠汤治疗气虚肠燥型功能性便秘安全有效。
Functional constipation (FC) is a more common functional gastrointestinal disorders, high incidence of the disease, the incidence of chronic constipation is about 6.07% in China, Europe and Oceania as high as 19.8%. Chronic constipation have negative impact on human physiology and psychological, seriously affecting people's quality of life,currently,western medicine lack of effective treatment. Traditional Chinese Medicine treatment of this disease lack of high-quality clinical trials. On the base of reviewing treatment and research on FC by TCM and modern medicine, this article considers that people with Qi asthenia and intestinal dryness is liable to suffer from FC and that Our lifestyle is very much to blame for constipation.On the basis of past experience, proposed treatment of Yiqirunchang for type functional constipation in order to "rebuild bowel regularity,".Through the observation of clinical cases, to prove the efficacy and safety of the treatment in order to sum up Chinese medicine theory and clinical expression advantages of functional constipation. This study has three parts:The first part is functional constipation literature review, namely the "Ancient Chinese medicine Books diagnosis and treatment of constipation " and " Present condition of mordern medicine Researches on FC "; the second part is systematic review, followed by details of the "Chinese Herb for functional constipation:a systematic review and Meta analysis"; The third part is a clinical observation on the treatment of Yiqirunchang decoction for functional constipation.
Theory:
Theory in Chinese ancient books about constipation summarized in this part. Especially on the pathophysiology、etiology and treatment of constipation in the view of TCM; Modern research development:include epidemiology (incidence, etiology and risk factors, health economics, medical burden, etc.), diagnostic criteria, disease classification, diagnosis search tools, treatment, problems etc. Give a comprehensive description of the current domestic and international research on the status of functional constipation.
Systematic Review:
To assess the efficacy and safety of Chinese herb for treating Chronic Functional constipation. The CNKI、CBM、VIP、Cochrane Library、Pubmed and EMBASE were searched electronically.Studies were included if they were randomized and quasi-randomized clinical trails.The quality of included studies was assessed according to the Cochrane Handbook5.0.2.21 trails fulled the inclusion criteria.The methodological quality was poor.The Chinese herb had significant effect on functional constipation compared with Gastrointestinal mortility drugs:relative risk and 95%CI:1.18[1.12,1.25] for effecative rate,1.59[1.35,1.88]for cure rate; the risk and 95%CI of effecative and cure rate are 1.18[1.10,1.27]、1.59[1.35,1.88]compared with cathartic; integrative medicine compared with Gastrointestinal mortility drugs:the risk and 95%CI:1.21[1.09,1.34]for effecative rate,1.41[1.11,1.79] for cure rate. Althrough systematic of the available evidence suggests that Chinese herb is effecative and safty in treating chronic functional constipation,well designed trail is lacking.
Clinical Observation:
Objective:To evaluate the efficacy and safety of Yiqirunchang decoction for Qi asthenia and intestinal dryness type functional constipation.
Methods:60 subjects were divided into two groups randomly:treatment group in which 30 cases were given"Yi qirunchang" decoction and control group in which 30 cases were treated by "Qi rong run chang" oral.The score of syndromes,adverse event and the change of colonic transit condition before and after treatment were observed.
Results:Four weeks after treatment,effective rate in treatment group and control group was 90.0% and 66.7%, and the onset time of catharsis in treatment group is more short than the control group, the difference being significant(P<0.05). Symptom score such as defecation interval, defecation effort,stool characters, fatigue, poor appetite,significantly improved compare with before treatment.Both of the two interventions can significantly improve colonic transit,but Yiqirunchang decoction is more excellent. Four weeks after drug withdrawal, no matter some index show the duration of efficacy in treatment group is better than control group,3 patients recurred in treatment group and 6 patients recurred in control group,the difference being not significant(P>0.05).
Adverse events:One observed case Suffering from intestinal obstruction in the control group, no serious adverse events were found in other included cases.
Conclusion:Yiqirunchang decoction for Qi asthenia and Intestinal dryness functional constipation is safe and effective. Although the systematic review and Meta analysis results suggest that Chinese Herb for FC is relatively safe and effective, but generally low quality of included studies, currently unable to obtain credible evidence.
理论研究：
中医古籍中有关便秘论述的整理：对秦汉至明清有代表性的中医古籍中对便秘的论述进行了系统梳理,从源及流,旁及各家,分五个部分。第一部分重点介绍《黄帝内经》和《诸病源侯论》中有关便秘生理病理及病因学的相关论述；第二部分,重点介绍《伤寒论》和《金匮要略》两书对便秘的论治特色；第三部分,主要介绍温病代表作《温病条辨》和《瘟疫论》治疗便秘的特点；第四部分,分别介绍刘完素、李东垣、张子和、朱丹溪等四位金元医家对便秘的论治；第五部分,主要介绍明清时期一些有代表性的医家对便秘的论治经验。
西医研究现状：从流行病学特点(发病率、病因及危险因素研究、卫生经济学、医疗负担等)、诊断标准、疾病分类、诊查手段、治疗措施、存在问题等方面,全面介绍了目前国内外对功能性便秘的研究现状。
系统评价：
随着循证医学的发展,应用系统评价方法对中医药疗效及安全性进行评价显得必要和迫切,目前国内外尚无对中医药治疗功能性便秘的系统评价。本研究旨在系统评价中药治疗功能性便秘的疗效及安全性。以国际Cochrane协作网公布的Cohrane Handbook5.0.2系统评价原则为指导,制订详细的检索策略、具体的纳入标准和评价标准,分别检索CNKI、CBM、VIP、Cochrane Library、Pubmed和EMBASE等数据库,对近20年国内外发表的中药治疗功能性便秘的随机对照试验进行系统评价和Meta分析。共纳入21个符合标准的研究,对其中6个研究的Meta分析结果提示中药治疗慢性功能性便秘的疗效优于促胃肠动力药,有效率RR及95%CI：1.18[1.12,1.25],痊愈率RR及95%CI：1.59[1.35,1.88]；与泻剂比较有效率RR及95%CI：1.18[1.10,1.27],痊愈率RR及95%CI：1.65[1.29,2.10]；中药联合促胃肠动力药与促胃肠动力药比较,有效率RR及95%CI：1.21[1.09,1.34],痊愈率RR及95%CI：1.41[1.11,1.79]。漏斗图分析提示,纳入研究存在一定的发表偏倚。有限的研究提示：中药治疗慢性功能性便秘安全有效,但因纳入研究的质量普遍不高,目前还不能得出较为可靠的结论。
临床研究：
目的：评价益气润肠方治疗气虚肠燥型功能性便秘的临床疗效及安全性。
方法：临床筛选气虚肠燥型功能性便秘受试者60例,随机分为治疗组30例和对照组30例,分别给予经验效方益气润肠汤及芪蓉润肠口服液治疗,疗程4周,随访4周,通过对通便效果、中医证候积分、结肠运输试验、安全性等指标的观察,比较两种方案对气虚肠燥型功能性便秘的治疗效果。
结果：
临床和证候学疗效：治疗组临床疗效的有效率和痊愈率(90.0%,46.7%)高于对照组(66.7%,20.0%),差异有统计学意义(P=0.04)。治疗组证候疗效的有效率和痊愈率(86.7%,46.7%)高于对照组(63.3%,16.7%),差异有统计学意义(分别为p=0.02、p=0.04)。治疗组平均起效时间26±13.9(小时),对照组37.2±30.3(小时),二者通便起效时间差异有统计学意义(P=0.027)。中药汤剂较芪蓉润肠口服液通便起效时间短。
持续稳定性疗效：疗程结束时,治疗组排便质量1级的受试者多于对照组,排便质量为3级的受试者低于对照组,二者差异均有统计学意义(分别为p=0.02、p=0.03)。两组第四周、第八周排便间隔时间均短于治疗前,差异有统计学意义(P<0.05)；治疗组第四周与第八周比较差异无统计学意义(P=0.12),对照组第四周与第八周比较差异有统计学意义(P<0.0001)。表明治疗组中药汤剂持续稳定性好。对照组复发率高于治疗组,但二者差异并无统计学意义(P=0.36),在预防复发方面治疗药物与对照药相当。
单项症状疗效：第八周随访时治疗组的排便费力症状积分与第四周比差异有统计学意义(P<0.001),对照组的排便间隔延长、排便费力、大便性状积分与第四周相比差异有统计学意义(P<0.05)。说明治疗组药物在改善排便费力方面持续稳定性差,对照药物改善排便间隔延长、排便费力、大便性状等方面持续稳定性差。疗程第四周,治疗组在排便间隔延长、排便费力、疲惫乏力、神疲懒言等症状积分值低于对照组,且差异有统计学意义(P<0.05)；疗程第八周,治疗组排便间隔延长、大便性状、疲惫乏力、神疲懒言等症状积分值低于对照组,差异有统计学意义(P<0.05)。
结肠传输试验疗效：治疗组结肠传输试验有效率高于对照组,差异有统计学意义(p=0.02),益气润肠汤剂在改善功能性便秘受试者结肠传输功能方面优于芪蓉润肠口服液。治疗组痊愈率高于对照组,二者差异无统计学意义(p=0.08)。治疗前两组24小时、48小时、72小时标志物存留数差异均无统计学意义(P>0.05)。治疗组治疗前后72小时、48小时标志物存留数差异有统计学意义(p<0.00001),24小时标记物存留数差异无统计学意义(P=0.58)。提示中药汤剂能明显改善结肠传输功能,在48、72小时时段尤为明显。对照组治疗前后24、48、72小时结肠标记物存留数差异均无统计学意义(P>0.05),提示芪蓉润肠口服液在改善结肠传输功能方面疗效不及中药汤剂。
不良反应：治疗期间对照组1例受试对象因便秘加重出现肠梗阻,退出试验；另有一例出现轻度腹泻、腹痛,未经特殊处理,自行缓解。治疗组有2例受试对象出现轻度腹痛、腹泻,减量服药后症状消失,两组均无严重不良事件发生。
结论：益气润肠汤治疗气虚肠燥型功能性便秘安全有效。
Functional constipation (FC) is a more common functional gastrointestinal disorders, high incidence of the disease, the incidence of chronic constipation is about 6.07% in China, Europe and Oceania as high as 19.8%. Chronic constipation have negative impact on human physiology and psychological, seriously affecting people's quality of life,currently,western medicine lack of effective treatment. Traditional Chinese Medicine treatment of this disease lack of high-quality clinical trials. On the base of reviewing treatment and research on FC by TCM and modern medicine, this article considers that people with Qi asthenia and intestinal dryness is liable to suffer from FC and that Our lifestyle is very much to blame for constipation.On the basis of past experience, proposed treatment of Yiqirunchang for type functional constipation in order to "rebuild bowel regularity,".Through the observation of clinical cases, to prove the efficacy and safety of the treatment in order to sum up Chinese medicine theory and clinical expression advantages of functional constipation. This study has three parts:The first part is functional constipation literature review, namely the "Ancient Chinese medicine Books diagnosis and treatment of constipation " and " Present condition of mordern medicine Researches on FC "; the second part is systematic review, followed by details of the "Chinese Herb for functional constipation:a systematic review and Meta analysis"; The third part is a clinical observation on the treatment of Yiqirunchang decoction for functional constipation.
Theory:
Theory in Chinese ancient books about constipation summarized in this part. Especially on the pathophysiology、etiology and treatment of constipation in the view of TCM; Modern research development:include epidemiology (incidence, etiology and risk factors, health economics, medical burden, etc.), diagnostic criteria, disease classification, diagnosis search tools, treatment, problems etc. Give a comprehensive description of the current domestic and international research on the status of functional constipation.
Systematic Review:
To assess the efficacy and safety of Chinese herb for treating Chronic Functional constipation. The CNKI、CBM、VIP、Cochrane Library、Pubmed and EMBASE were searched electronically.Studies were included if they were randomized and quasi-randomized clinical trails.The quality of included studies was assessed according to the Cochrane Handbook5.0.2.21 trails fulled the inclusion criteria.The methodological quality was poor.The Chinese herb had significant effect on functional constipation compared with Gastrointestinal mortility drugs:relative risk and 95%CI:1.18[1.12,1.25] for effecative rate,1.59[1.35,1.88]for cure rate; the risk and 95%CI of effecative and cure rate are 1.18[1.10,1.27]、1.59[1.35,1.88]compared with cathartic; integrative medicine compared with Gastrointestinal mortility drugs:the risk and 95%CI:1.21[1.09,1.34]for effecative rate,1.41[1.11,1.79] for cure rate. Althrough systematic of the available evidence suggests that Chinese herb is effecative and safty in treating chronic functional constipation,well designed trail is lacking.
Clinical Observation:
Objective:To evaluate the efficacy and safety of Yiqirunchang decoction for Qi asthenia and intestinal dryness type functional constipation.
Methods:60 subjects were divided into two groups randomly:treatment group in which 30 cases were given"Yi qirunchang" decoction and control group in which 30 cases were treated by "Qi rong run chang" oral.The score of syndromes,adverse event and the change of colonic transit condition before and after treatment were observed.
Results:Four weeks after treatment,effective rate in treatment group and control group was 90.0% and 66.7%, and the onset time of catharsis in treatment group is more short than the control group, the difference being significant(P<0.05). Symptom score such as defecation interval, defecation effort,stool characters, fatigue, poor appetite,significantly improved compare with before treatment.Both of the two interventions can significantly improve colonic transit,but Yiqirunchang decoction is more excellent. Four weeks after drug withdrawal, no matter some index show the duration of efficacy in treatment group is better than control group,3 patients recurred in treatment group and 6 patients recurred in control group,the difference being not significant(P>0.05).
Adverse events:One observed case Suffering from intestinal obstruction in the control group, no serious adverse events were found in other included cases.
Conclusion:Yiqirunchang decoction for Qi asthenia and Intestinal dryness functional constipation is safe and effective. Although the systematic review and Meta analysis results suggest that Chinese Herb for FC is relatively safe and effective, but generally low quality of included studies, currently unable to obtain credible evidence.
引文
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