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肠易激综合征证候规律与脑肠肽相关性的临床研究
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摘要
背景:
     肠易激综合征是一组临床症候群,主要表现为腹痛、腹胀不适以及大便次数增多、粪质稀薄等腹泻表现,或大便难排、粪质干结等便秘表现,或者腹泻与便秘交替出现等。而实验室等检查无明显异常,缺乏特异性的诊断指标。肠易激综合征的发病机制复杂,面对各种亚型西药治疗效果欠佳,症状易反复发作。中医药运用整体观念、辨证论治等方法在改善症状等方面有不错的疗效;进一步研究该病的发病机制、中医证候规律,能够提高疾病的诊疗水平;对多项现代实验指标的研究,能够综合评定多个指标与肠易激综合征发病的相关性,以期能够通过现代检验手段阐明肠易激综合征中医肝郁脾虚、脾胃虚弱等证的本质,同时挖掘这些指标之间的相关性,促进中医药的现代化发展。
     目的:
     探索肠易激综合征的中医证候规律,通过临床信息采集,观察肠易激综合征的证候特点,总结其中规律,完善肠易激综合征的中医辨证论治体系。对相关指标进行检测,研究这些指标是否参与肠易激综合征的发病过程,以及研究这些指标之间的相关性,分析这些指标与中医辨证之间的联系,为进一步探讨肠易激综合征的发病机制提供客观依据。
     方法:
     本研究采用临床调查方法,分为两部分;第一部分为证候规律部分,第二部分为检验指标部分。证候规律部分参考了社会调查研究的相关理论与方法,期间查阅整理了大量中医文献资料以及国内外最新研究进展,咨询专家教授的指导意见,最终建立信息表与数据库,内容包括一般信息、病史特征、全身表现、二便情况、腹部症状、腰部症状、精神状态、舌脉情况等。检验指标项目包括促肾上腺皮质激素、血管紧张素Ⅱ、5-羟色胺、糖皮质激素、褪黑素、一氧化氮、同型半胱氨酸、肿瘤坏死因子-α、神经肽Y。对临床研究信息表与检验结果进行整理归纳,采用方差分析、秩和检验、因子分析、主成分分析、聚类分析、多元相关分析等统计学方法,研究肠易激综合征患者症状、体征等方面的特点及规律,探寻5-羟色胺、血管紧张素Ⅱ等现代检验指标在肠易激综合征患者中的含量,探讨指标之间的联系,与不同亚型、不同中医证型的相关性。
     结果:
     一、证候方面
     (一)共纳入病例149例,男性63人(42.3%),平均年龄33.34±13.80岁;女性86人(57.7%),平均年龄43.93±13.66岁。149例IBS患者的平均病程为4.7±5.5年。50.3%的人认为本病有加重因素,饮食不慎、受凉、焦虑、紧张、烦躁不安是常见的加重因素。
     (二)在肠易激综合征患者亚型分布中,以腹泻型最为常见,占88.6%,便秘型患者占7.4%,混合型患者占2.7%,不确定型患者占1.3%。中医证型方面,从单一证型分析脾虚证占77.3%,肝郁证占47.7%;从复合证型分析,肝郁脾虚证占47.7%,脾虚湿阻证占24.2%。IBS-D患者常见的症状:痛泻(85.6%)、腹痛(77.3%)、紧张(70.5%)、矢气频(64.4%)等;舌脉情况舌边有齿痕占55.0%,舌苔白腻占63.8%,脉无力占41.6%,脉软占35.6%。在IBS男性患者中烦躁者占44.3%,紧张者占24.2%,精神抑郁者占18.1%。
     (三)综合因子分析、聚类分析结果,肝郁脾虚、脾胃虚弱、脾虚湿阻是主要病机特点。患者遇寒受凉会加重完谷不化的症状(P<0.05)。IBS-D患者精神症状越重,消化道症状越明显(P<0.05)。
     二、检验指标分析
     (一)ACTH、5-HT、GC、MT、NO、HCY、TNF-α、NPY的含量在腹泻型、便秘型、交替型三种亚型之间差异无统计学意义(P>0.05)。
     (二)ACTH、AT-Ⅱ、5-HT、GC、MT、NO、HCY、TNF-α、NPY在腹泻型患者肝郁脾虚、脾胃虚弱、脾虚湿阻三种证型的含量差异无统计学意义(P>0.05)。
     (三)AT-Ⅱ在腹泻型患者中男性比女性含量高(P<0.05),而ACTH、5-HT、GC、MT、 NO、HCY、TNF-α、NPY在性别中差异无统计学意义(P>0.05)。
     (四)ACTH、AT-Ⅱ、5-HT、GC、MT、NO、HCY、TNF-α、NPY水平高低与泄泻的次数、粪质、腹痛程度、腹胀不适等消化系统症状严重程度无相关性(P>0.05)。ACTH、AT-Ⅱ、5-HT、GC、MT、NO、HCY、TNF-α、NPY水平高低与患者烦躁、急躁易怒、精神抑郁、焦虑等精神症状的严重程度无相关性(P>0.05)。主成分分析显示5-HT、HCY、TNF-α、ACTH、MT、GC是IBS检验指标中的重要指标。聚类分析结果显示,如聚为4类则第一类为ACTH、NPY;第二类为AT-Ⅱ、GC、HCY、MT;第三类为NO、TNF-α;第四类为5-HT。如果聚为3类则第一类为ACTH、NPY;第二类为AT-Ⅱ、GC、HCY、MT、NO、 TNF-α;第三类为5-HT。从分类的间距看,分为2类较为合适,即第一类:ACTH、NPY、 AT-Ⅱ、GC、HCY、MT、NO、TNF-α.第二类:5-HT。
     结论:
     一、证候方面
     (一)腹泻型是肠易激综合征四种亚型中最常见的亚型。
     (二)饮食不慎、受凉、焦虑、紧张、烦躁不安是常见的加重因素。IBS患者多伴有情绪精神症状改变。
     (三)肝郁脾虚是本病的常见证型,脾虚是发病的基础,肝郁是常见的影响因素。腹泻型患者烦躁、精神抑郁、忧郁、焦虑等精神症状越重,腹痛、腹泻等消化道症状越明显。
     二、检验指标分析
     (一)ACTH、AT-Ⅱ、5-HT、GC、MT、NO、HCY、TNF-α、NPY在腹泻型、便秘型、交替型三种亚型之间差异无统计学意义。
     (二)ACTH、AT-Ⅱ、5-HT、GC、MT、NO、HCY、TNF-α、NPY在腹泻型患者肝郁脾虚证、脾胃虚弱证、脾虚湿阻证三种常见证型中的含量差异无统计学意义。
     (三)AT-Ⅱ在腹泻型患者中男性比女性含量高,而ACTH、5-HT、GC、MT、NO、HCY、 TNF-α、NPY在性别中差异无统计学意义。
     (四)ACTH、AT-Ⅱ、5-HT、GC、MT、NO、HCY、TNF-α、NPY与泄泻的次数、粪质稀薄、腹痛、腹胀不适等消化系统症状的严重程度无相关性。5-HT、HCY、TNF-α、ACTH、 MT、GC是IBS检验指标中的重要指标。检验指标如分为四类:第一类为ACTH、NPY;第二类为AT-Ⅱ、GC、HCY、MT;第三类为NO、TNF-α;第四类为5-HT。如分为3类则第一类为ACTH、NPY;第二类为AT-Ⅱ、GC、HCY、MT、NO、TNF-α;第三类为5-HT。如分为2类则第一类为ACTH、NPY、AT-Ⅱ、GC、HCY、MT、NO、TNF-α;第二类为5-HT。
Background
     Irritable bowel syndrome is a symptom-based diagnosis characterized by chronic abdominal pain, discomfort, bloating, and change of bowel habits. There is no obvious morphological and biochemical characteristics of the test in the diagnosis of this disease. Modern medicine has not been fully effects of drugs for treatment of this disease in different subtypes. In terms of treatment, the use of holism and treatment based on syndrome differentiation of Traditional Chinese Medicine has made a good effect. The study of pathogenesis, symptoms can improve the level of diagnosis and treatment. To study various laboratory tests may find syndrome of liver-depression and spleen-deficiency, weakness of the spleen and stomach syndrome and other syndromes nature. Analysis the correlation between these test projects can promote to develop the modernization of TCM.
     Objective
     Analysis of the patient's clinical symptoms and signs, summed medical evidence law, can further improve medical diagnosis and treatment of IBS. In order to further explore the pathogenesis of IBS, testing blood indicators to study the correlation between these indicators, and to find the correlations between these indicators and Traditional Chinese Medicine.
     Method
     In this study,the clinical investigation is divided into two parts, the first part is a symptom research component, the second part is the indicators component. The first reference to the relevant theories and methods of social research, sorting through a large number of Chinese literature, as well as the latest research progress at home and abroad, consulting experts and professors, guidance, and ultimately establish information table and database. Contents include:general information,history, physical examination, the overall symptoms, head facial symptoms, symptoms of chest, abdomen, waist and limb symptoms, diet flavors, mainland conditions, mental symptoms, tongue and pulse condition, etc. Blood testing include:5-serotonin, corticosteroids, angiotensinⅡ, adrenocorticotropic hormone, melatonin, homocysteine, tumor necrosis factor-alpha, nitric oxide,neuropeptide Y. Through the analysis of variance, factor analysis, principal component analysis and cluster analysis, correlation analysis and other statistical methods, finishing summed up the information sheet and test results.
     Result
     1. TCM symptoms
     1.1A total of149cases, including63male patients(42.3%), mean age33.34+13.80years;86females(57.7%), mean age43.93±13.66years old. The average duration of the149patients with IBS patients was4.7±5.5years.50.3%of people think that there were aggravating factors. Food accidentally, cold, anxiety, tension, irritability were common aggravating factors.
     1.2IBS-D was the most common type, accounting for88.6%. IBS-C accounted for7.4%, IBS-M accounted for2.7%, IBS-U accounted for1.3%. In Chinese medicine, the spleen deficiency syndrome accounted for77.3%, hepatic depression syndrome accounted for47.7%; syndrome of liver-depression and spleen-deficiency accounted for47.7%, weakness of the spleen and stomach syndrome accounted for24.2%.
     1.3After factor analysis, clustering results of the analysis, syndrome of liver-depression and spleen-deficiency,weakness of the spleen and stomach syndrome, spleen deficiency and dampness syndrome are the characteristics of TCM's pathogenesis. The heavier mental symptoms in patients with IBS-D, the more severe gastrointestinal symptoms.
     2. Analysis of test indicators
     2.1ACTH, AT-Ⅱ,5-HT, GC, MT, NO, HCY, TNF-α, NPY, these indicators have no significant differences in groups of IBS-C, IBS-D, IBS-M subtypes (P>0.05).
     2.2ACTH, AT-Ⅱ,5-HT, GC, MT, NO, HCY, TNF-α, NPY, these indicators have no significant differences in groups of liver-depression and spleen-deficiency syndrome, weakness of the spleen and stomach syndrome, spleen deficiency and dampness syndrome(P>0.05).
     2.3In IBS-D group, men's level of AT-Ⅱ is higher than women's (P<0.05). ACTH,5-HT, GC, MT, NO, HCY, TNF-α, NPY have no significant differences in gender (P>0.05).
     2.4The level of ACTH, AT-Ⅱ,5-HT, GC, MT, NO, HCY, TNF-α, NPY and diarrhea, stool, abdominal pain, bloating and other digestive symptoms severity were no correlations (P>0.05). The level of ACTH, AT-Ⅱ,5-HT, GC, MT, NO, HCY, TNF-α, NPY and irritability, depression, anxiety and other psychiatric symptoms severity were no correlations(P>0.05). Principal component analysis showed that5-HT, HCY, TNF-alpha, ACTH, MT, GC were important indexes of IBS test indexes. Cluster analysis showed that divided into four categories:the first category ACTH, NPY; second category AT-Ⅱ, GC, HCY, MT;third category NO, TNF-α; fourth category5-HT. Divided into three categories:the first category ACTH, NPY; second category AT-Ⅱ, GC, HCY, MT, NO, TNF-α; third category5-HT. Divided into two categories:ACTH,NPY, AT-II, GC, HCY, MT, NO, TNF-α normalized as a class;5-HT classified as a class.
     Conclusion
     1. TCM symptoms
     1.1IBS-D is the most common subtype of the four subtypes.
     1.2Common aggravating factors include careless diet, cold, anxiety, tension, irritability. Patients often accompanied by changes in psychiatric symptoms.
     1.3The syndrome of liver-depression and spleen-deficiency is most common syndrome of this disease. Insufficiency of the spleen is the basis of the disease. Liver stagnation is a common influencing factor.
     1.4The level of ACTH, AT-Ⅱ,5-HT, GC, MT, NO, HCY, TNF-α, NPY and diarrhea, stool, abdominal pain, bloating and other digestive symptoms severity are no correlations. The inspection indicators can be divided into two types of ACTH, NPY,AT-Ⅱ,GC,HCY,MT,NO, TNF-α and5-HT.
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