本文選題：脾胃濕熱　切入點：病機轉化　出處：《湖北中醫(yī)藥大學》2017年博士論文

【摘要】：目的Hp相關性胃炎的發(fā)展存在這樣一種病理演進路徑:慢性非萎縮性胃炎一慢性萎縮性胃炎一腸上皮化生一不典型增生一癌變。當前大部分中醫(yī)學者認為Hp與脾胃濕熱關系密切,從中醫(yī)的病因理論看,Hp應當是一種濕熱病邪,Hp相關性胃炎與濕熱溫病關系緊密。葉天士在《臨證指南醫(yī)案》中提出“初病濕熱在經,久則瘀熱入絡”,尤在涇在《金匱要略心典》中也有:“無邪不有毒,熱從毒化,變從毒起,瘀從毒結也”的觀點。濕熱致病病程綿長,逐漸生變。濕熱之邪侵犯人體,其初起病情較為輕淺,但濕熱膠結、蘊蒸日久則化瘀化毒、瘀毒互結,入里入絡,致使疾病日趨嚴重。濕熱化毒瘀似乎和Hp相關性胃炎的病理演變有某種暗合。中醫(yī)推崇上工治未病,如何從中醫(yī)溫病理論中發(fā)掘Hp相關性胃炎的發(fā)病規(guī)律?Hp相關性胃炎向胃癌發(fā)展過程中是否伴隨有濕熱化毒瘀的過程?這種轉化存在客觀物質基礎嗎?本課題圍繞這些核心問題展開,在分析傳統(tǒng)中醫(yī)經典理論和現(xiàn)代中醫(yī)學者研究的基礎上,從中發(fā)掘Hp相關性胃炎脾胃濕熱證病機轉化的規(guī)律,同時采用代謝組學研究的方法,尋找脾胃濕熱及濕熱轉化的相關物質基礎。方法1.理論研究:在梳理了中醫(yī)濕熱病的發(fā)展與源流后,我們集中整理了明清溫病學家所闡發(fā)的相關理論,并對現(xiàn)代中醫(yī)學者有關Hp相關性胃炎的相關研究進行分類總結。2.代謝組學研究:采集2015年1月至2016年1月在武漢地區(qū)5家醫(yī)院確診的慢性胃炎、胃癌患者各100例,進行14C尿素呼氣試驗檢測Hp、胃鏡檢查等,并進行中醫(yī)辨證分型。入選實驗對象為符合納入標準的脾胃濕熱型慢性胃炎患者20例,脾胃濕熱型胃癌患者20例,另選取在武漢市中醫(yī)醫(yī)院保健科體檢的健康人群20例設為健康對照組。EP管收集符合納入標準的患者及健康志愿者的中段晨尿10ml,采集尿液的核磁譜圖,對得到的相關數(shù)據采用pca和pls-da進行分析并驗證。結果1.理論研究結果1.1脾胃濕熱病機的主要轉化方式盡管新感溫病和伏氣溫病在發(fā)病上有所不同,但在濕熱病機的傳變方面并沒有太大差異。從衛(wèi)氣營血辨證來看,脾胃濕熱證會向營血分發(fā)展,也可能因治療得當,在氣分而愈。從三焦辨證看,脾胃濕熱證發(fā)生在中焦脾胃,可以蘊蒸其中“在一經不移”,也可以向下傳及下焦之臟肝腎或下焦之腑大腸、小腸、膀胱;還可以向上傳及肺、心包、腦。從經絡來看,脾胃濕熱證拖延日久,會出現(xiàn)久病入絡,合并血瘀證�！皩崉t陽明,虛則太陰”,脾胃陽氣的強盛與否影響著脾胃濕熱證的轉化方向。再者,體質類型影響著脾胃濕熱證的轉歸結局,陰虛之人出現(xiàn)脾胃濕熱容易陰液更虧,最終出現(xiàn)陰虛風動證,陽虛之人的脾胃濕熱證最終出現(xiàn)腎陽虛。體質條件對脾胃濕熱證的發(fā)生、轉化和結局有至關重要的影響。1.2hp相關性胃炎至胃癌的中醫(yī)病機轉化研究hp感染通過不同的作用機制導致慢性胃炎,在疾病的后果及嚴重程度上除了細菌因素起重要作用外,宿主的免疫反應也是hp相關性疾病發(fā)生,特別是胃癌發(fā)生的重要決定因素。hp在胃黏膜定植后,在其繁殖、孳生、蔓延的過程中分泌毒素,暗耗人體陰陽氣血,破壞人體平衡。hp所致胃病的發(fā)病特點符合溫病中伏氣溫病的特點,發(fā)病過程中隱現(xiàn)濕熱化毒瘀的病機轉化規(guī)律。2.代謝組學研究結果2.1一般情況在進行證候判別、病理分級確診病例并篩選后,入選實驗對象60例,分為a、c、d三個組,每組20例。a組為脾胃濕熱型慢性胃炎組,c組為脾胃濕熱型胃癌組,d組為健康對照組。三組人員在性別、年齡、體重指數(shù)上的差異無統(tǒng)計學意義。2.2代謝組學分析結果本實驗通過對樣本的1h-nmr譜圖進行分析,并對其種類進行歸類后,找到可以定性定量的代謝物共59種:Ⅰ.氨基酸及其衍生物(20種);Ⅱ.氨基化合物與混合胺(9種);Ⅲ.糖類(5種);Ⅳ.有機酸類(15種);Ⅴ.其他類(10種)。通過對三組人員進行尿液代謝組學檢測分析發(fā)現(xiàn):在pca圖中可以看到健康對照組與胃炎組,健康對照組與胃癌組有分開趨勢,但胃炎組與胃癌組兩組樣本無法分離,進一步通過pls-da分析方法發(fā)現(xiàn)胃炎組與胃癌組樣本有分開趨勢,胃癌組與健康對照組樣本有分開趨勢,胃炎組與健康對照組樣本分離。并通過vip圖等找到三組尿液中差異代謝物11種,最后篩選出8種代謝物的差異具有顯著性意義,分別是:巖藻糖、磷酸肌酸、馬尿酸、甘油、葫蘆巴堿、�；撬帷⒀趸装�、n-苯乙酰甘氨酸。通過對脾胃濕熱證組(a+c組)和健康對照組(d組)進行尿液代謝組學檢測分析,在pca得分圖中可以看出脾胃濕熱證組與健康對照組樣本有分開趨勢。進一步在pls-da得分圖中可以看出,脾胃濕熱證組樣本和健康對照組樣本明顯分離,說明其代謝輪廓相異。并通過vip圖等找到兩組尿液中差異代謝物12種,最后篩選出8種代謝物為脾胃濕熱證的潛在生物標志物:馬尿酸、�；撬帷r藻糖、甘油、葫蘆巴堿、氧化三甲胺、磷酸肌酸、葡萄糖。相對于健康對照組而言,脾胃濕熱證組中上調的差異代謝物為:牛磺酸、巖藻糖、甘油、氧化三甲胺、葡萄糖。下調的差異代謝物為:馬尿酸、葫蘆巴堿、磷酸肌酸。結論1、從溫病的經典著作和現(xiàn)代中醫(yī)學者的研究總結來看,hp相關性胃炎濕熱病機傳變在總體上呈現(xiàn)這一趨勢:濕熱久蘊,正氣日損,瘀毒漸生。2、hp作為致病因素可以歸屬于濕熱伏氣,hp相關性胃炎更容易形成脾胃濕熱證,hp的發(fā)作與它的毒素基因類型有關,也與宿主的體質緊密相關,陽虛質、氣虛質、痰濕質、濕熱質患者更易罹患本病,hp相關性胃病發(fā)展與濕熱化毒瘀,正氣耗損有關。3、脾胃濕熱證組與健康對照組的代謝組學差異提示脾胃濕熱證存在客觀物質基礎。慢性胃炎脾胃濕熱證與胃癌脾胃濕熱證的代謝組學差異表明二者病機不盡相同,也說明病機有病的特殊性。病機的轉化往往早于證的表現(xiàn)。4、中醫(yī)的優(yōu)勢在于對于疾病發(fā)生發(fā)展整體性、恒動性的認知和針對病患個體進行差異性的施治。揭示疾病的中醫(yī)病機,尤其是疾病轉化規(guī)律,從而尋找到關鍵的治療節(jié)點具有重要的臨床價值。
[Abstract]:Development of Hp associated gastritis there is a pathological evolution path: chronic non atrophic gastritis of chronic atrophic gastritis with intestinal metaplasia is a typical hyperplasia of cancer. Most Chinese scholars believe that Hp and spleen is closely related to the etiology of Chinese medicine theory, Hp should be a damp heat pathogen. Hp associated gastritis and damp febrile disease closely. Ye Tianshi in "a guide to clinical practice" proposed "disease early in the long, damp heat, blood stasis and heat in collaterals", but also in the < you Zaijing jinkuiyaolue > heart Code: "innocent not poisonous, heat from the poison from poison, poison from blood stasis is the" point of view. Damp heat pathogenic lingering course and gradually changed. Damp heat invading the body, its initial condition is more shallow, but in the course of time the steam heat cements, removing blood stasis toxin, and blood stasis, enters into the network, resulting in the disease has become increasingly serious. Heat of the poison and blood stasis appears to Hp Pathological gastritis evolution has some coincidence. Respected Chinese work zhiweibing, how to explore the pathogenesis of Hp related gastritis from epidemic febrile disease of TCM theory? Hp gastritis to gastric cancer development process is accompanied by the process of heat toxin and blood stasis? This existed in the transformation of the objective material basis? This paper focuses on these core issues based on the analysis, the classical theory of traditional Chinese medicine and modern Chinese scholars, from which to explore the correlation between Hp of spleen stomach damp heat syndrome pathogenesis transformation rules, at the same time by using the method of Metabonomics Study for hot and damp heat, spleen stomach damp transformation related material basis. Methods: 1. theoretical research in combing the origin and development of traditional Chinese medicine damp heat disease, we focus on studying the theories on Febrile Diseases by the elucidation of the Ming and Qing Dynasties, and summarize the related research about the classification of.2. Hp associated gastritis of modern Chinese scholars Metabonomic study: from January 2015 to January 2016 in 5 hospitals in Wuhan were diagnosed as chronic gastritis, gastric cancer in 100 cases, 14C urea breath test Hp, gastroscopy, and TCM syndrome type. The subjects were selected in accordance with the inclusion of 20 patients with spleen stomach damp heat syndrome of chronic gastritis and 20 cases of the standard. Patients with spleen stomach damp heat syndrome of gastric cancer, and other selected in the healthy population of Wuhan City Health Department of Chinese medicine hospital physical examination of 20 cases of healthy controls were collected.EP tube met the inclusion criteria of patients and healthy volunteers midpiece urine 10ml, urine collection of NMR spectra, the data obtained by PCA and PLS-DA to analyze and verify the main way of transformation. Results of the 1. theoretical research results 1.1 pathogenesis of spleen stomach damp heat despite the new sense of febrile disease and epidemic febrile diseases in the pathogenesis of different, but in the pathogenesis of damp heat transfer and there is no big difference Different from weiqiyingxue syndrome, spleen stomach damp heat syndrome to camp blood development, may also be due to proper treatment in gas and more. From Sanjiao differentiation of spleen stomach damp heat syndrome, occur in the spleen and stomach, which can accumulate in the steam does not move "once, can also pass and coke the liver kidney or lower Jiao Fu large intestine, small intestine, bladder and lung; also be able to upload, pericardium, brain. From the point of view of meridian, spleen and stomach damp heat syndrome delay time, there will be long into the network, combined with blood stasis syndrome." in Yangming, deficiency of Spleen Yang Taiyin, strong or not affects the transformation the direction of spleen stomach damp heat syndrome. Furthermore, physical type affects the outcome of spleen stomach damp heat syndrome, yin deficiency of Yin fluid more easily appear spleen deficient, eventually Yin pneumatic syndrome, Yang of spleen stomach damp heat syndrome of kidney yang deficiency constitution. Finally conditions on spleen stomach damp heat syndrome occurrence, transformation and ending to Influence of TCM pathogenesis of.1.2hp associated gastritis to gastric cancer transformation of HP infection through different mechanisms leading to chronic gastritis, in consequence of the disease and the severity in bacterial factors play an important role, the host immune response is associated with HP disease, especially the incidence of gastric cancer were important determinants of.Hp in the stomach in the mucosa after planting, breeding, breeding, the spread of toxin secretion in the process of human consumption of dark Yin and Yang Qi and blood, body balance caused by.Hp damage incidence characteristics of stomach in line with the characteristics of epidemic febrile disease of disease of the ambush gas, pathogenesis and transformation.2. metabolomics incidence in the process of looming heat of the poison stasis in the general case 2.1 the syndrome identification, pathology confirmed cases and screening, 60 cases of experimental subjects, divided into a, C, d three groups, 20 cases each group.A spleen stomach damp heat syndrome of chronic gastritis group, C group of spleen and stomach Damp heat type gastric cancer group, D group as the healthy control group. Three groups in gender, age, body mass index of the difference was not statistically significant.2.2 metabolomics analysis results of the experiment based on the sample were analyzed by 1H-NMR spectra, and the species were classified, can be found in qualitative and quantitative metabolite 59 of amino acid and its derivatives (20); II. Amino compounds with mixed amine (9); 3. Sugar (5); IV. Organic acids (15 kinds); v. Other classes (10). The three groups were urine metabolomics analysis found: in the the PCA map can be seen in the healthy control group and gastritis group, healthy control group and gastric cancer group have separate trend, but the gastritis group and gastric cancer group, two groups of samples can not be separated, further found that the gastritis group and gastric cancer group samples were separated by the method of PLS-DA trend analysis, gastric cancer group and healthy control group samples have separate trend of stomach With control group sample separation group and health. And through the VIP map to find the differences between the three groups of urine metabolites in 11, and screen out the difference between the 8 kinds of metabolites were significant, respectively is: fucose, phosphocreatine, hippuric acid, glycerol, trigonelline, taurine, trimethylamine oxide, n- phenylacetylglycine. Based on the SSDH syndrome group (a+c group) and control group (Group D) urine metabonomic analysis detection, the PCA score plot can be seen in the spleen and stomach damp heat syndrome group and healthy control group samples have separate trend. Further can be seen in the PLS-DA score plot, spleen stomach damp heat syndrome group samples and healthy control group the sample was separated, the metabolic profile differences. And through the VIP map to find the differences between the two groups of urine metabolites in 12, finally screened potential biomarkers for 8 metabolites of spleen stomach damp heat syndrome: hippuric acid, taurine, fucose, glycerol , trigonelline, trimethylamine oxide, creatine phosphate, glucose. Compared with healthy control group, the difference in metabolite up-regulated in splenogastric damp heat syndrome is: taurine, fucose, glycerol, trimethylamine, oxidation of glucose. The difference is: cut the metabolites of hippuric acid, trigonelline, phosphocreatine. Conclusion: 1, from the research of febrile disease the classics and modern Chinese scholars summarize, pathogenesis of Hp associated gastritis of damp heat transfer has the same trend in general: Long Yun Qi, damp heat, blood stasis and toxin damage, getting.2, HP as pathogenic factors can be attributed to wet heat volt gas, Hp associated gastritis easier formation of spleen stomach damp heat syndrome, HP attack toxin gene type and its related, also with the host body is closely related to Yang deficiency, Qi deficiency, phlegm dampness, damp heat patients more prone to the disease, HP gastropathy development and heat of the poison and blood stasis, Qi depletion of.3, spleen and stomach damp heat syndrome The metabolism of group and healthy control group studies suggest that the difference of spleen stomach damp heat syndrome of the existence of objective material basis. Metabolic chronic gastritis with spleen stomach damp heat syndrome of spleen stomach damp heat syndrome differentiation of gastric cancer showed that the two diseases are not the same, also shows that the particularity of the pathogenesis of disease. The pathogenesis of transformation often early in the performance of the.4 card the advantage of traditional Chinese medicine, the disease occurrence and development of the overall, permanent change of cognition and individual differences in patient treatment. To reveal the pathogenesis of the disease, especially the disease transformation rules, in order to find the key node treatment has important clinical value.

【學位授予單位】：湖北中醫(yī)藥大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R259

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