本文選題：冠心病 + 五臟相關(guān)��； 參考：《廣州中醫(yī)藥大學(xué)》2016年博士論文

【摘要】：目的：梳理吳煥林教授對(duì)國(guó)醫(yī)大師鄧鐵濤五臟相關(guān)學(xué)說(shuō)治療冠心病的繼承和發(fā)展；運(yùn)用數(shù)據(jù)挖掘的方法,分析吳煥林教授在五臟相關(guān)理論指導(dǎo)下治療冠心病的臨床用藥規(guī)律；將臨床用藥規(guī)律挖掘結(jié)果與學(xué)術(shù)理論互證,確定實(shí)驗(yàn)藥物,對(duì)藥物的抗血小板聚集、抗動(dòng)脈血栓形成的作用及機(jī)理進(jìn)行探討,為臨床用藥經(jīng)驗(yàn)提供依據(jù)。方法：學(xué)術(shù)思想研究主要通過(guò)文獻(xiàn)分析及跟診師承的方法,梳理五臟相關(guān)治療冠心病的源流與發(fā)展。運(yùn)用數(shù)據(jù)挖掘技術(shù)對(duì)臨床用藥規(guī)律分析研究根據(jù)納入、排除標(biāo)準(zhǔn),對(duì)吳煥林教授醫(yī)案進(jìn)行采集、標(biāo)準(zhǔn)化和結(jié)構(gòu)化,形成規(guī)范可用的數(shù)據(jù)庫(kù)；運(yùn)用中醫(yī)傳承輔助平臺(tái)軟件對(duì)醫(yī)案用藥進(jìn)行四氣統(tǒng)計(jì)、五味統(tǒng)計(jì)、歸經(jīng)統(tǒng)計(jì)、基于關(guān)聯(lián)規(guī)則的藥物模式分析及規(guī)則分析、基于改進(jìn)的互信息法的藥物的關(guān)聯(lián)度分析、基于復(fù)雜系統(tǒng)熵聚類的藥物提取組合分析、基于無(wú)監(jiān)督熵層次聚類的新方組合分析。實(shí)驗(yàn)研究將66只SPF級(jí)SD大鼠隨機(jī)分為6組,分別是空白組、高劑量組、中劑量組、低劑量組、陽(yáng)性對(duì)照組,每組12只,模型組為6只,干預(yù)7天。將模型組全組、半數(shù)的高、中、低劑量組、半數(shù)的陽(yáng)性對(duì)照組給予三氯化鐵外敷法頸動(dòng)脈血栓造模,半數(shù)的空白組給予假手術(shù)對(duì)照,監(jiān)測(cè)頸動(dòng)脈血流、石蠟病理切片及HE染色,分析實(shí)驗(yàn)藥物體內(nèi)抗動(dòng)脈血栓的療效；其余的動(dòng)物給藥干預(yù)7天后,腹主動(dòng)脈取血,通過(guò)血小板聚集率檢測(cè)、血小板cAMP的ELISA檢測(cè)、PI3K-Akt及PKC-Erk通路蛋白western blot檢測(cè),分析實(shí)驗(yàn)藥物抗血小板的機(jī)制。結(jié)果：五臟相關(guān)學(xué)說(shuō)是在五行學(xué)說(shuō)的基礎(chǔ)上發(fā)展而來(lái),指以五臟為中心的五個(gè)系統(tǒng)內(nèi)部、五個(gè)系統(tǒng)之間、五個(gè)系統(tǒng)與機(jī)體、與自然界、與社會(huì)相互影響與制約。在傳承和發(fā)展的基礎(chǔ)上,五臟相關(guān)治療冠心病的臨證思想可分為三個(gè)階段：心肝相關(guān)階段,心脾相關(guān)階段、心肺腎相關(guān)階段,注重每一階段的主要受病臟腑和臨床特征。在每個(gè)不同的階段,有著不同的病機(jī)、不同的治則治法和方藥。用藥規(guī)律研究：共納入了1044條方,191味藥物。使用頻率大于100次的藥物有41味；藥物歸經(jīng)依次主要為脾、胃、肺、肝、心、腎；藥物四氣歸類依次為：溫、平、涼、寒、熱；藥物五味歸類依次為：甘、苦、辛、淡、咸、酸�；陉P(guān)聯(lián)規(guī)則的用藥模式分析,將支持度設(shè)為550,得到藥物模式45個(gè),涉及7味藥；將支持度設(shè)為500,涉及8味藥；將支持度設(shè)為450,涉及9味藥。藥物的規(guī)則分析,支持度為550,置信度為0.90的藥物規(guī)則101個(gè)；置信度大于0.98的藥物規(guī)則38個(gè)�；诟倪M(jìn)的互信息法的藥物的關(guān)聯(lián)度分析,將相關(guān)度設(shè)為8,懲罰度設(shè)為2,得到關(guān)聯(lián)系數(shù)大于0.03的藥對(duì)24個(gè)�；趶�(fù)雜系統(tǒng)熵聚類的藥物提取組合分析,得到3-4味藥物的核心組合20個(gè)；通過(guò)無(wú)監(jiān)督的熵層次聚類算法,得到潛在的新方組合10個(gè)。Omin頸動(dòng)脈基礎(chǔ)血流,各個(gè)組間沒(méi)有差異(P0.05),15min頸動(dòng)脈血流監(jiān)測(cè)表明,實(shí)驗(yàn)藥物高劑量組增加造模后頸動(dòng)脈的血流量(P0.05)；25min頸動(dòng)脈血流監(jiān)測(cè)表明,實(shí)驗(yàn)藥物中、高劑量組增加造模后頸動(dòng)脈的血流量(P0.01)。石蠟切片及HE染色結(jié)果表明,實(shí)驗(yàn)藥物呈劑量依賴性的減少造模后頸動(dòng)脈內(nèi)的血栓量。實(shí)驗(yàn)藥物中、高劑量組降低血小板聚集率(P0.05,P0.01)。進(jìn)一步研究發(fā)現(xiàn),與ADP組比較,高劑量組小板內(nèi)cAMP的含量升高(P0.01)。蛋白免疫印跡結(jié)果分析表明,實(shí)驗(yàn)藥物高劑量組可降低血小板內(nèi)PI3Kp110β的表達(dá)量(P0.05)。高劑量組使得血小板內(nèi)p-Akt/t- Akt表達(dá)量降低(P0.01)。與ADP組相比,實(shí)驗(yàn)藥物的低、中、高劑量組皆不能改變血小板內(nèi)p-pkc的表達(dá)量(P0.05)。實(shí)驗(yàn)藥物的高劑量組可以降低血小板內(nèi)p-erk/t- erk的表達(dá)量(P0.05)。結(jié)論：五臟相關(guān)學(xué)說(shuō)源于五行學(xué)說(shuō),基于五行學(xué)說(shuō)的局限性及臨床實(shí)踐的需求,五臟相關(guān)學(xué)說(shuō)孕育而生,吳煥林教授對(duì)五臟相關(guān)治療冠心病在原來(lái)基礎(chǔ)上進(jìn)行了細(xì)化和發(fā)展,漸漸成為較成熟的理論。用藥規(guī)律挖掘：在心脾階段病例占較大比例的前提下,藥物以益氣健脾、化痰濕、活血類藥物為主,藥物歸經(jīng)以脾、胃、肺、肝、心、腎為主；四氣以溫、平為主;五味以甘、苦、辛為主。挖掘出了主要藥物模式、藥物規(guī)則、關(guān)聯(lián)藥對(duì)、藥物提取組合、潛在的新方等,采用人機(jī)對(duì)話的形式,得出用藥規(guī)律,可以較好的指導(dǎo)臨床。實(shí)驗(yàn)研究：實(shí)驗(yàn)藥物具有抗SD大鼠頸動(dòng)脈血栓形成的作用；抑制血小板激活,降低血小板聚集率,其機(jī)制可能是上調(diào)cAMP表達(dá)水平,抑制了PI3K-Akt-erk信號(hào)通路的激活。
[Abstract]:Objective: to sort out professor Wu Huanlin's inheritance and development of the Deng Tietao five Zang related theory in the treatment of coronary heart disease, and the method of data mining to analyze the clinical medication rule of Professor Wu Huanlin in the treatment of coronary heart disease under the guidance of the related theory of five zang organs. The effect and mechanism of antiplatelet aggregation and anti arterial thrombosis are discussed, and the basis for clinical use of drugs is provided. Methods: the study of academic thought mainly through the literature analysis and the method of following up with the doctor, combing the origin and development of coronary heart disease related to the five zang organs related treatment. The application of data mining technology to the clinical drug use law analysis According to the inclusion and exclusion criteria, the medical cases of Professor Wu Huanlin were collected, standardized and structured to form a standardized database, and the traditional Chinese Medicine Inheritance auxiliary platform software was used to make four statistics, five statistics, statistics, drug model analysis based on association rules and rules analysis based on association rules, based on improved mutual information. Analysis of the degree of association of the drugs, based on the combination analysis of drug extraction with complex system entropy clustering, based on the combination analysis of the unsupervised entropy hierarchical clustering. 66 SPF grade SD rats were randomly divided into 6 groups, which were blank group, high dose group, middle dose group, low dose group, positive control group, 12 rats in each group, 6 rats in model group and 7 intervention. 7 The whole group of the model group, half of the high, middle and low dose group, half of the positive control group were given the carotid artery thrombosis with iron trichloride external application, half of the blank groups were given the sham operation control, the blood flow of the carotid artery, the pathological section of paraffin and HE staining, the effect of the anti arterial thrombosis in the experimental drugs were analyzed; the rest of the animals were given 7 intervention. After the abdominal aorta, the blood was taken from the abdominal aorta, the platelet aggregation rate was detected, the ELISA detection of platelet cAMP, the PI3K-Akt and the PKC-Erk pathway protein Western blot were detected, and the mechanism of antiplatelet antiplatelet agents was analyzed. Results: the five organs related theory developed on the basis of the five line theory, which refers to the five internal organs and five systems with the five viscera as the center. Between the five systems and the body, and the nature, and society mutual influence and restriction. On the basis of inheritance and development, the five organs related to the treatment of coronary heart disease can be divided into three stages: the related stage of the heart and the liver, the related stage of the heart and the spleen, the related stage of the heart and the lung and the kidney, and pay attention to the main viscera and clinical features of each stage. At the same stage, there were different pathogenesis, different treatment rules and prescriptions. Study on the rule of drug use: a total of 1044 prescriptions and 191 flavors were included. The drugs used in more than 100 times were 41 flavors; the drugs were mainly divided into spleen, stomach, lung, liver, heart and kidney in turn: warm, flat, cold, cold, and heat, and the five flavors of drugs were classified in turn. Gump, bitterness, symplectic, light, salty, acid. Based on the association rules of the drug model analysis, the support was set to 550, the drug model was set to 45, involving 7 flavors; the support was set to 500, and the support was set to 450, involving 9 drugs. The drug rule analysis, the support degree of 550, the confidence degree 0.90 of the drug rules 101; confidence greater than 0.9. 8 drug rule 38. Based on the correlation analysis of improved mutual information method, the correlation degree is set to 8, the penalty degree is set to 2, and the correlation coefficient is more than 0.03 to 24. The combination analysis of drug extraction based on the entropy clustering of complex system is obtained, and 20 core combinations of the 3-4 flavors are obtained. Through the unsupervised entropy hierarchical clustering algorithm, the results are obtained. The potential new side combined 10.Omin carotid artery base blood flow, and there was no difference between each group (P0.05). 15min carotid artery blood flow monitoring showed that the high dose group increased the blood flow of the carotid artery (P0.05) in the high dose group, and the 25min carotid artery blood flow monitoring showed that the high dose group increased the blood flow of the carotid artery (P0.01) in the high dose group (P0.01) and paraffin wax. The results of slicing and HE staining showed that the experimental drug was dose-dependent to reduce the volume of thrombus in the carotid artery. In the experimental drug, the high dose group reduced the platelet aggregation rate (P0.05, P0.01). Further studies found that the content of cAMP in the high dose group was higher than that in the ADP group (P0.01). The results of protein immunoblotting showed that the experiment was carried out. The high dose group could reduce the expression of PI3Kp110 beta in the platelet (P0.05). The high dose group reduced the expression of p-Akt/t- Akt in the platelets (P0.01). Compared with the ADP group, the low, middle and high dose groups of the experimental drugs could not change the p-pkc expression in the platelets (P0.05). The high dose group of the experimental drugs could reduce the p-erk/t- ER in the platelets. K expression (P0.05). Conclusion: the theory of five zang organs related to the theory of five elements, based on the limitations of the five line theory and the needs of clinical practice, the five Zang related theories gestation and birth, Professor Wu Huanlin on the five Zang related treatment of coronary heart disease on the basis of the original refinement and development, gradually become a more mature theory. On the premise of a large proportion of the spleen stage cases, the drug is based on Invigorating Qi to invigorate the spleen, eliminating phlegm dampness and activating blood type drugs. The drugs are mainly treated with spleen, stomach, lung, liver, heart and kidney; the four gases are mainly warm and flat; five flavors are Gump, bitter and symplectic. In the form of machine dialogue, the rule of drug use can be obtained to guide the clinical. Experimental study: experimental drugs have the effect of anti SD rat carotid thrombosis, inhibit platelet activation, reduce platelet aggregation rate, its mechanism may be up regulation of cAMP expression and inhibit the activation of PI3K-Akt-erk signaling pathway.

【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R249;R259

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