本文選題：蒙定水 + 冠心病�。� 參考：《廣州中醫(yī)藥大學(xué)》2016年博士論文

【摘要】：目的：筆者非常有幸成為第五批全國名老中醫(yī)藥專家學(xué)術(shù)經(jīng)驗(yàn)繼承人,師承名老中醫(yī)蒙定水教授。并榮幸的成為廣州中醫(yī)藥大學(xué)周福生教授的弟子。在周教授的精心指導(dǎo)下,作者主要從蒙定水教授學(xué)術(shù)師承溯源著手,以冠心病為主攻方向,較系統(tǒng)地挖掘整理蒙教授關(guān)于冠心病病因病機(jī)“五臟關(guān)聯(lián)辨證觀”,“無虛不發(fā)病”、“無瘀不發(fā)病”,與“益氣升陽活血治法”新觀點(diǎn),以及辨治冠心病的組方規(guī)律與用藥特點(diǎn)等學(xué)術(shù)思想與臨證經(jīng)驗(yàn)。受蒙教授的學(xué)術(shù)思想影響和熏陶,筆者近年來主要致力于冠心病“益氣升陽活血法”的臨床療效與作用機(jī)理研究,并將其運(yùn)用于治療冠心病的臨床實(shí)踐中。同時(shí)分別從文獻(xiàn)整理、臨床療效評價(jià)及作用機(jī)理等三個(gè)方面來深入研究探討,以期進(jìn)一步豐富和發(fā)展冠心病的中醫(yī)病因病機(jī)及辨證論治的理論內(nèi)涵。冠狀動(dòng)脈粥樣硬化性心臟病簡稱冠心病(CHD),是指因冠狀動(dòng)脈粥樣硬化(AS)而致冠脈血管狹窄或閉塞,進(jìn)而導(dǎo)致心肌缺血、缺氧引起的心臟病。本病是一種由遺傳因素和環(huán)境因素共同作用引起的復(fù)雜疾病,目前已經(jīng)成為全球范圍內(nèi)死亡和致殘的首要病因。關(guān)于其發(fā)病機(jī)制目前普遍認(rèn)為與血管內(nèi)皮功能紊亂,血小板活化、炎癥反應(yīng)、斑塊破裂、血栓形成以及血清脂質(zhì)代謝異常密切相關(guān)。現(xiàn)代醫(yī)學(xué)治療主要有藥物治療和血運(yùn)重建(包括PCI和CABG術(shù)),雖然取得了長足進(jìn)展。但介入治療目前仍存在許多無法克服的問題,如介入術(shù)后再狹窄的問題,冠脈微血管病變和多支彌漫性病變無法植入支架等問題,仍有不少患者不能達(dá)到完全血運(yùn)重建而影響預(yù)后。中醫(yī)藥治療冠心病主要針對多部位、多靶點(diǎn)和雙向調(diào)節(jié)等方面起作用,臨床療效顯著,具有現(xiàn)代醫(yī)學(xué)不可比擬的優(yōu)勢,目前已經(jīng)受到國內(nèi)外醫(yī)學(xué)者普遍關(guān)注和重視。本課題是在前期臨床研究工作的基礎(chǔ)上,采用隨機(jī)、盲法、安慰劑對照的研究方法,以期證明益氣升陽活血中藥加味丹葛止痛方治療冠心病穩(wěn)定型心絞痛是否具有絕對的有效性和安全性。通過人工實(shí)驗(yàn)動(dòng)物造模成功后,并觀察加味丹葛止痛方對氣虛血瘀證急性心肌梗死大鼠模型血漿ET、NO的影響,以及對心肌梗死邊緣區(qū)缺血心肌微血管新生的影響,從較深層次研究探討中醫(yī)藥治療冠心病的作用機(jī)理,為益氣升陽活血中藥加味丹葛止痛方治療冠心病的現(xiàn)代病理生理機(jī)制提供可靠的理論依據(jù)。同時(shí)該研究亦能進(jìn)一步為中醫(yī)益氣升陽活血法治療冠心病提供更有力的實(shí)驗(yàn)證據(jù)。方法：本課題分為臨床研究和實(shí)驗(yàn)研究兩大部分。1臨床研究方法：將符合納入標(biāo)準(zhǔn)的冠心病穩(wěn)定型心絞痛氣虛血瘀證患者64例,按照1：1的比例隨機(jī)分為兩組即治療組和對照組,每組各32例,治療組予以加味丹葛止痛方顆�？诜�,對照組予以安慰劑口服,采用隨機(jī)、盲法、安慰劑對照的臨床研究,并追蹤隨訪,主要從臨床心絞痛癥狀、中醫(yī)證候積分、西雅圖量表評分、心絞痛發(fā)作次數(shù)與持續(xù)時(shí)間、硝酸甘油服用量與服藥后心絞痛緩解的時(shí)間以及對患者血脂水平、血清Hs-CRP和血液流變學(xué)等多項(xiàng)指標(biāo)評價(jià)中藥加味丹葛止痛方的臨床療效。觀察療程為4周,隨訪周期6個(gè)月。2實(shí)驗(yàn)研究方法：參照文獻(xiàn)法先復(fù)制實(shí)驗(yàn)大鼠氣虛血瘀證模型,復(fù)制成功后再采用結(jié)扎模型大鼠冠狀動(dòng)脈左前降支復(fù)制急性心肌梗死模型,然后將復(fù)制成功的氣虛血瘀證AMI模型大鼠(除去死亡外)40只隨機(jī)分為4組,即假手術(shù)組、模型組、加味丹葛止痛方(簡稱治療組)和芪參益氣滴丸組(簡稱對照組)。治療組給予常規(guī)治療劑量的加味丹葛止痛方藥液灌胃,對照組予以常規(guī)治療劑量的芪參益氣滴丸藥液灌胃,假手術(shù)組和模型組給予等體積溶液生理鹽水灌胃,給藥時(shí)間為2周,每日1次。用藥期間密切大鼠一般情況,用藥結(jié)束后觀察大鼠治療前后血漿NO、ET水平,采用HE染色觀察氣虛血瘀證AMI模型大鼠心肌組織病理形態(tài)改變,采用免疫組化法觀察氣虛血瘀證AMI模型大鼠心肌梗死邊緣區(qū)缺血心肌微血管新生情況。結(jié)果：1臨床研究結(jié)果1.1對冠心病穩(wěn)定型心絞痛的胸悶、胸痛,心悸氣短、神疲乏力等癥狀的改善更加明顯：經(jīng)過4周的治療,通過西雅圖心絞痛量表評分及中醫(yī)證候積分比較,兩組患者的各個(gè)癥狀都有明顯改善,與對照組比較,治療組的各個(gè)癥狀的改善程度較對照組改善更為明顯。1.2心絞痛發(fā)作的頻率、持續(xù)時(shí)間及硝酸甘油服用量與服藥后心絞痛緩解的時(shí)間均明顯減少：通過對患者進(jìn)行4周的治療觀察,發(fā)現(xiàn)兩組患者心絞痛發(fā)作的頻率、持續(xù)時(shí)間及硝酸甘油服用量與服藥后心絞痛的緩解時(shí)間均有明顯減少。與對照組比較,結(jié)果顯示治療組上述指標(biāo)減少更明顯。1.3對患者實(shí)驗(yàn)室指標(biāo)的改善更明顯：經(jīng)過4周1療程的治療觀察,發(fā)現(xiàn)兩組患者血清血脂中TC、TG、LDL-C均明顯降低,HDL-C明顯升高,以及Hs-CRP均明顯降低,血液流變學(xué)各項(xiàng)指標(biāo)均較治療前有明顯改善。與對照組比較,治療組上述各項(xiàng)指標(biāo)改善更明顯。1.4治療藥物安全、且無明顯毒副作用：經(jīng)過4周一療程的治療觀察,發(fā)現(xiàn)兩組患者均未發(fā)生不良事件和不良反應(yīng),實(shí)驗(yàn)室的各項(xiàng)安全指標(biāo)檢查均為正常,表明中藥加味丹葛止痛方顆粒治療冠心病穩(wěn)定型心絞痛氣虛血瘀證安全有效。2實(shí)驗(yàn)研究結(jié)果：經(jīng)過1療程的治療后,治療組與對照組兩組大鼠血漿ET水平均明顯降低,血漿NO水平明顯升高,與模型組比較,差異有統(tǒng)計(jì)學(xué)意義(PO.01)。且加味丹葛止痛方組前兩項(xiàng)指標(biāo)改善更明顯,但與對照組比較,差異無顯著性(P0.05)。除假手術(shù)組外,造模各組大鼠心肌梗死邊緣區(qū)心肌內(nèi)皮細(xì)胞CD34表達(dá)明顯增強(qiáng),MVC顯著增加,提示急性心肌缺血后血管新生過程已經(jīng)啟動(dòng)。加味丹葛止痛方組和芪參益氣滴丸組大鼠急性心肌梗死邊緣區(qū)缺血心肌微血管新生明顯增加,缺血心肌內(nèi)皮細(xì)胞數(shù)／微血管數(shù)(MVC)和微血管面積(MVD)明顯增多,與模型組比較,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。與芪參益氣滴丸組比較,加味丹葛止痛方組心肌梗死大鼠缺血心肌內(nèi)皮細(xì)胞數(shù)(MVC)和MVD明顯增加,但差異無統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論：1中藥加味丹葛止痛方治療冠心病穩(wěn)定型心絞痛氣虛血瘀證臨床療效顯著,可以明顯減輕患者心絞痛的癥狀,降低心絞痛的中醫(yī)證候積分,減少心絞痛發(fā)作的次數(shù)及持續(xù)時(shí)間,減少硝酸甘油服用量與服藥后心絞痛緩解時(shí)間,并能降低患者血脂水平、降低血清Hs-CRP和改善血液流變學(xué)指標(biāo),且藥物安全無毒副作用。2中藥加味丹葛止痛方治療實(shí)驗(yàn)急性心肌梗死模型大鼠,能顯著提高其血漿N0水平,降低其血漿ET水平；并能促進(jìn)急性心肌梗死邊緣區(qū)缺血心肌微血管新生,增加缺血心肌內(nèi)皮細(xì)胞數(shù)／微血管數(shù)(MVC)和微血管面積(MVD)。表明加味丹葛止痛方對急性心肌梗死缺血心肌具有較好的保護(hù)作用。綜合上述結(jié)果,考慮中藥加味丹葛止痛方可能通過促進(jìn)冠心病患者急性心肌梗死血缺血邊緣區(qū)微血管新生,從而促進(jìn)冠狀動(dòng)脈側(cè)枝循環(huán)的建立；糾正NO/ET比例的失衡而對缺血心肌組織起保護(hù)作用,進(jìn)而改善冠心病患者的臨床癥狀,減少心絞痛發(fā)作次數(shù)及持續(xù)時(shí)間等。也更深層次證實(shí)益氣升陽活血法指導(dǎo)下創(chuàng)建的加味丹葛止痛方對氣虛血瘀證冠心病患者臨床療效顯著,為益氣升陽活血法治療冠心病氣虛血瘀證提供了更有力的證據(jù)。
[Abstract]:Objective: the author is very fortunate to be the fifth batch of the successor to the academic experience of Chinese traditional Chinese medicine experts, Professor Meng Ding Shui, a professor of the famous old Chinese medicine, and a disciple of Professor Zhou Fusheng of Guangzhou University of Chinese Medicine. Under the careful guidance of Professor Zhou, the author mainly starts from the academic division of Professor Meng Ding Shui and mainly focuses on the attack of coronary heart disease. To systematically excavate the academic thoughts and experience of Professor Meng's academic thought on the syndrome differentiation of the five zang organs, "no deficiency and no disease", "no blood stasis and no disease", the new viewpoint of "promoting Qi Yang and activating blood circulation method", as well as the prescription and drug characteristics of coronary heart disease, and other academic thoughts and clinical experience. In recent years, the author is mainly devoted to the study of the clinical effect and mechanism of "Yiqi Yang activating blood activating method", and it is used in the clinical practice of treating coronary heart disease. At the same time, it is studied in three aspects, including literature sorting, clinical efficacy evaluation and mechanism of action, in order to further enrich and develop coronary heart disease. Coronary atherosclerotic heart disease (CHD) refers to coronary artery stenosis or occlusion caused by coronary atherosclerosis (AS), which leads to myocardial ischemia and hypoxia induced heart disease. This disease is caused by a combination of genetic factors and environmental factors. Miscellaneous diseases have now become the leading cause of death and disability worldwide. Its pathogenesis is generally believed to be closely related to vascular endothelial dysfunction, platelet activation, inflammatory reaction, plaque rupture, thrombosis and serum lipid metabolism. Modern medical treatment mainly includes drug treatment and blood transport reconstruction. Although great progress has been made in PCI and CABG, there are still many problems that can not be overcome, such as the problems of restenosis after interventional procedure, coronary microvascular lesions and multiple diffuse lesions that can not be implanted into the stent. Many patients still can not achieve complete revascularization and affect the prognosis. Chinese medicine for the treatment of coronary heart disease is the main problem. In view of the role of multi site, multi target and two-way regulation, the clinical curative effect is remarkable, and it has an incomparable advantage in modern medicine. At present, it has been paid much attention to and paid attention to by the medical researchers both at home and abroad. This topic is based on the earlier clinical research work, using random, blind, placebo control research methods, with a view to prove the benefit. The effect and safety of Qi Yang Huoxue Chinese medicine plus Zhisan Zhitong prescription in the treatment of coronary stable angina pectoris. After the success of artificial animal models, the effects of gisan Ge Zhitong Recipe on the plasma ET, NO in the rat model of acute myocardial infarction with Qi deficiency and blood stasis syndrome, and the ischemic myocardium in the marginal zone of myocardial infarction were observed. The effect of microvascular neovascularization, the mechanism of traditional Chinese medicine treatment of coronary heart disease was studied from a deeper level, and a reliable theoretical basis was provided for the modern pathophysiological mechanism of coronary heart disease treated with Yiqi Shengyang Huoxue traditional Chinese medicine and Gudan Zhitong prescription. Experimental evidence of force. Methods: the subject was divided into two.1 clinical research methods: clinical research and experimental research: 64 patients with coronary heart disease stable angina pectoris Qi deficiency and blood stasis syndrome were divided into two groups according to the proportion of 1:1, the treatment group and the control group, each group was divided into 32 cases, and the treatment group was given the decoction of Gudan Ge Zhitong. Orally, the control group was given a placebo orally, using a randomized, blind, placebo controlled clinical study and followed up, mainly from clinical angina symptoms, TCM syndrome scores, Seattle scale score, the frequency and duration of angina pectoris, the time of the dosage of nitroglycerin and the remission of angina pectoris after the medication and the blood lipid of the patients. Levels, serum Hs-CRP and hemorheology and other indexes were used to evaluate the clinical effect of Chinese herbal medicine plus Gudan Ge Zhitong prescription. The treatment course was 4 weeks, and the follow-up period was 6 months.2 experimental research method: the experimental model of qi deficiency and blood stasis syndrome was replicated by the reference method, and the acute coronary artery left anterior descending branch of the model rats was replicated after the replication of the model. The model of myocardial infarction was then divided into 4 groups randomly: AMI model rats (excluding death) of qi deficiency and blood stasis syndrome, which were divided into 4 groups randomly, namely, sham operation group, model group, Gutan Kishi Fang (treatment group) and Qi Shen Yiqi dropping pill group (abbreviated as control group). The treatment group was given gutta gutta Zhitong prescription in the treatment group, and the control group was given to the control group. The conventional treatment dose of Qi Shen Yiqi dropping pill was given to the stomach. The sham operation group and the model group were given the same volume of saline solution for 2 weeks, 1 times a day. During the medication, the blood plasma NO and ET were observed before and after the treatment, and the AMI model rats of qi deficiency and blood stasis syndrome were observed by HE staining. Pathological changes of myocardial tissue and immunohistochemical method were used to observe the microvasculature of ischemic myocardium in the marginal zone of AMI model rats with Qi deficiency and blood stasis syndrome. Results 1 clinical results 1.1 improved the symptoms such as chest tightness, chest pain, palpitation, palpitation, fatigue and other symptoms of coronary heart disease stable angina pectoris. After 4 weeks of treatment, By comparing the score of Seattle angina scale and TCM syndrome score, the symptoms of the two groups were obviously improved. Compared with the control group, the improvement of each symptom in the treatment group was more obvious than that of the control group. The duration of the treatment and the time of the use of nitroglycerin and the time of relieving the angina pectoris after the treatment were more obvious than that of the control group. By 4 weeks of treatment, the frequency of angina pectoris in the two groups, duration of nitroglycerin and the time of remission of angina pectoris were significantly reduced in the two groups. The results showed that the reduction of the above indexes in the treatment group was more obvious in the improvement of the laboratory index of.1.3. More obvious: after 4 weeks of 1 courses of treatment observation, it was found that TC, TG, LDL-C in serum lipids of the two groups were significantly decreased, HDL-C was significantly increased, and Hs-CRP was significantly reduced. All indexes of blood rheology were significantly improved compared with those before treatment. Compared with the control group, the indexes of the treatment group improved more obviously with the safety of.1.4 treatment, and no Obvious toxic and side effects: after 4 Monday courses of treatment observation, the two groups of patients were found to have no adverse events and adverse reactions, and all the laboratory safety indexes were all normal. The results showed that the traditional Chinese medicine plus zhitadong Zhitong granule in the treatment of coronary heart disease stable angina pectoris Qi deficiency and blood stasis syndrome.2 experimental results: after 1 courses of treatment After treatment, the plasma ET level of the two groups in the treatment group and the control group were significantly reduced, the plasma NO level was significantly increased, and the difference was statistically significant (PO.01) compared with the model group. And the first two indexes of the group were more obvious, but compared with the control group, the difference was not significant (P0.05). Except for the sham operation group, the model rats were made in each group. The expression of CD34 in myocardial endothelial cells in the marginal zone of myocardial infarction was obviously enhanced and MVC increased significantly, suggesting that the angiogenesis process had started after acute myocardial ischemia. The microvasculature of ischemic myocardium in the marginal zone of acute myocardial infarction in the group of gisorudan Ge Zhitong and Qi Shen Yiqi dropping pills group increased significantly, and the number of endothelial cells / microvessels in the ischemic myocardium was the number of microvessels. (MVC) and microvascular area (MVD) significantly increased, compared with the model group, the difference was statistically significant (P0.05). Compared with the Qisheng Yiqi dropping pill group, the number of ischemic myocardium (MVC) and MVD in the rats with myocardial infarction increased significantly, but the difference was not significant (P0.05). Conclusion: 1 Chinese medicine plus gisan Ge Zhitong prescription treatment crown The clinical curative effect of qi deficiency and blood stasis syndrome of angina pectoris stable angina is significant. It can obviously reduce the symptoms of angina pectoris, reduce the score of TCM syndrome, reduce the frequency and duration of angina pectoris, reduce the dosage of nitroglycerin and the time of relieving angina pectoris, and reduce the level of blood lipid, reduce the Hs-CRP and the serum level of the patients. The improvement of blood rheology index, drug safety and non-toxic side effect.2 Chinese herbal medicine plus Zhisan Zhitong prescription can significantly improve the level of plasma N0 and reduce the level of plasma ET, and can promote the microvascular neovascularization of the ischemic myocardium in the marginal area of acute myocardial infarction and increase the number of ischemic myocardial endothelial cells / Microblood. The number of tubes (MVC) and microvascular area (MVD) showed that gisan Ge Zhitong prescription had a good protective effect on the ischemic myocardium of acute myocardial infarction. To correct the imbalance of NO/ET ratio and to protect the ischemic myocardium, to improve the clinical symptoms of the patients with coronary heart disease, to reduce the frequency and duration of angina pectoris, and to further prove the clinical effect of gisan Ge Zhitong, which was created under the guidance of the method of solid gas promotion and blood activating, on the patients with Qi deficiency and blood stasis syndrome. It provides more convincing evidence for the treatment of qi deficiency and blood stasis syndrome of coronary heart disease by supplementing qi, Promoting Yang and activating blood circulation.
【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R249;R259

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4 王京良;何龍登;;回春益氣補(bǔ)陽片聯(lián)合中藥治療胃下垂[A];中國中西醫(yī)結(jié)合學(xué)會第十四次全國消化系統(tǒng)疾病學(xué)術(shù)研討會論文匯編[C];2002年

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2 河北省雞澤縣中西醫(yī)結(jié)合醫(yī)院 高莉　孟憲紅 高敬力;升陽益氣治療頑固性頭痛[N];中國中醫(yī)藥報(bào);2011年

3 劉緒銀 湖南省新邵縣中醫(yī)院;甘溫益氣 升降透發(fā)除大熱[N];中國中醫(yī)藥報(bào);2012年

4 孫法泰;益氣升陽固脫法治療慢性直腸炎[N];中國中醫(yī)藥報(bào);2003年

5 ;五類眼疾中醫(yī)支招[N];上海中醫(yī)藥報(bào);2007年

6 江蘇姜堰市中醫(yī)院主任醫(yī)師 謝兆豐;益氣升陽療“呵欠”[N];家庭醫(yī)生報(bào);2003年

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1 黃修解;蒙定水教授益氣升陽活血法治療CHD的臨床觀察與作用機(jī)理探討[D];廣州中醫(yī)藥大學(xué);2016年

2 遲繼銘;補(bǔ)脾益氣升陽對糖尿病腎病炎癥反應(yīng)的干預(yù)作用[D];黑龍江中醫(yī)藥大學(xué);2007年

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2 張巖巖;補(bǔ)脾益氣升陽方對糖尿病腎病患者尿PCX、VEGF的影響[D];黑龍江省中醫(yī)研究院;2009年

3 徐丹;補(bǔ)脾益氣升陽方對糖尿病腎病大鼠尿CRP和MIF的影響[D];黑龍江省中醫(yī)研究院;2008年

4 肖政華;益氣升陽法對D-半乳糖衰老小鼠免疫功能的影響及抗自由基作用的實(shí)驗(yàn)研究[D];貴陽中醫(yī)學(xué)院;2007年

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