發(fā)布時間：2018-03-17 12:12

  本文選題：療效機制　切入點：microRNA　出處：《北京中醫(yī)藥大學(xué)》2016年博士論文　論文類型：學(xué)位論文

【摘要】：研究目的：總結(jié)和整理蘇榮扎布教授學(xué)術(shù)思想及臨床經(jīng)驗；觀察研究蘇榮扎布驗方與心身互動療法結(jié)合治療心刺痛病的臨床療效,并探討其療效機制。研究方法和研究內(nèi)容:1.通過整理蘇老師艱苦的生活、學(xué)習(xí)、行醫(yī)、教學(xué)等生活和成長經(jīng)歷,感悟這些特殊的生活經(jīng)歷對老師的人格形成以及成為國醫(yī)大師的影響作用；學(xué)習(xí)和研究蘇老師的論文、專著等文獻,分析和總結(jié)蘇老師學(xué)術(shù)思想淵源及其特點,在此基礎(chǔ)上就蒙醫(yī)整體觀思想和醫(yī)學(xué)模式提出繼承人自己的新見解。2.通過閱讀蘇老師的論文、專著和相關(guān)蒙醫(yī)經(jīng)典著作以及跟導(dǎo)師出門診學(xué)習(xí),篩選出導(dǎo)師擅長治療的11個優(yōu)勢病種,闡述導(dǎo)師對這些疾病的病因分析、癥狀觀察以及治療的特點和優(yōu)勢,并從每個病種選擇兩個典型病例予以分析,從而總結(jié)和歸納導(dǎo)師的學(xué)術(shù)思想和臨床經(jīng)驗特點。再對老師診療過的190名心刺痛病患者從病因病機、病型特點、治則治法、護理要點和用藥特點、組方使用頻率以及療程方面進行回顧性研究,總結(jié)老師治療心刺痛病的學(xué)術(shù)思想和臨床經(jīng)驗,并提出蘇老師驗方結(jié)合心身互動療法治療心刺痛病的新方法。3.根據(jù)診斷標(biāo)準(zhǔn)選擇90名心刺痛病患者,隨機分為蘇老師治療組(蒙藥組)、蘇老師驗方與心身互動療法結(jié)合治療組(觀察組)和丹參滴丸治療組(對照組)三組,每組30名,七天為一個療程,共三個療程。通過觀察臨床癥狀、心電圖以及SCL90心理量表等指標(biāo),對照三組的臨床療效。4.在以上臨床研究的基礎(chǔ)上,對觀察組6名心刺痛病患者治療前與治療后的血清microRNA表達進行分析,探討其療效機制。又取6名正常人血清樣本作為對照組來使用。具體操作為每人抽取10ml血樣,分離血清,從血清提取總RNA,進行基因芯片(Microarray)檢測,做生物信息學(xué)分析。結(jié)果：1.蘇老師學(xué)術(shù)思想總結(jié)：蘇老師最突出的學(xué)術(shù)思想是關(guān)于蒙醫(yī)整體觀思想的豐富與發(fā)展。蘇老師于1980年發(fā)表了“關(guān)于蒙醫(yī)學(xué)整體觀思想的初談”為題目的論文,使他成為現(xiàn)代蒙醫(yī)學(xué)領(lǐng)域中最早研究蒙醫(yī)學(xué)整體觀思想的學(xué)者。蘇老師提出了“以陰陽學(xué)說為基礎(chǔ)的蒙醫(yī)整體觀思想是蒙醫(yī)學(xué)理論的要點所在。人與自然的相關(guān)性、五行與三根的相關(guān)性、三根與七素三穢的相關(guān)性是它的基本內(nèi)涵。和三根與七素關(guān)系相關(guān)聯(lián)的‘精濁代謝’理論是其精髓也�！睆亩S富和發(fā)展了現(xiàn)代蒙醫(yī)學(xué)整體觀理論內(nèi)涵。蘇老師的典型學(xué)術(shù)思想還體現(xiàn)在：以尋根治源為根本：以把握赫依的治療為關(guān)鍵點；以促進氣血運行疏通經(jīng)脈為具體步驟：調(diào)解胃火與體素間平衡為目的；重視清除陳熱；注重心理作用；心-身-言三業(yè)相結(jié)合；強調(diào)養(yǎng)生保健等共9個方面。學(xué)習(xí)中感悟到,蘇老師是一名博學(xué)多識、臨床經(jīng)驗豐富且具有自身獨特思維特點和診療技術(shù)的一代蒙醫(yī)大師。除技術(shù)以外他的大慈大悲、仁心仁術(shù)等做人品德和人格魅力也是造就他成長為國醫(yī)大師的主要因素所在。在導(dǎo)師的指點下,縱覽蒙醫(yī)學(xué)理論,本人就蒙醫(yī)學(xué)整體觀思想的結(jié)構(gòu)提出：“人體內(nèi)部的整體統(tǒng)一、身與心的整體統(tǒng)一、人與社會的整體統(tǒng)一、人與自然的整體統(tǒng)一和人與宇宙(時間和空間)的整體統(tǒng)一”等五個層面的新見解,又從這樣的理解進一步推理、思考醫(yī)學(xué)模式問題,認(rèn)為蒙醫(yī)學(xué)醫(yī)學(xué)模式應(yīng)該關(guān)系到：“生物-心理-社會自然-時空(宇宙)”五維結(jié)構(gòu)組成的新觀點。2.蘇老師臨床經(jīng)驗總結(jié)：通過文獻整理和跟師學(xué)習(xí),對蘇老師最擅長診治的心刺痛病,心律失常,心肌炎,腎結(jié)石,慢性支氣管炎,慢性胃炎,失眠癥,神志病,癲癇病,月經(jīng)不調(diào),子宮肌瘤等十一個病種的概念、病因分析、癥狀觀察以及辯證治療的闡述中總結(jié)了蘇老師的獨到見解和診療經(jīng)驗、手法特點。發(fā)現(xiàn)蘇老師在綜合運用治病四施,靈活聯(lián)合用藥,巧妙調(diào)配藥引子等辯證施治方面的特色較為突出。對蘇老師最擅長治療的心刺痛病進行回顧性研究,總結(jié)出以下7個內(nèi)容。①病因病機和病型特點：蘇老師認(rèn)為導(dǎo)致冠脈阻塞的最根本原因是精濁代謝不良,濁物黏著在血管壁所致；此病在臨床上以赫依和其素合并型為居多。②治則治法：主要以助胃火、促進精濁代謝,疏通經(jīng)脈改善氣血循環(huán),鎮(zhèn)痛及針對具體病情辯證論治。③常用藥方組合模式：早：吉如很希莫吉樂10粒,浩道敦-10味丸或壯西-14味丸10粒；午：新—Ⅱ號13粒,贊丹-7味湯1.5克,伊和湯1.5克；晚：額日敦烏日勒15粒,阿嘎日-35味散3克。④使用頻率最高的前6位藥方為：額日敦烏日勒100%,阿嘎日-35味散100%,伊和湯95.3,吉如很希莫吉樂89.5%,新—Ⅱ號68.9%,贊丹-7味湯57.9%。⑤辯證施治常見藥方：失眠用蘇格木勒-4味湯,胃脹用毛勒日達布斯-4味湯,心悸用書沙-7味丸或阿敏額日敦,咳嗽用沏其日-11味散或薩楚-3味散,有風(fēng)濕樣酸痛感用森登-4味湯、查千古古勒-10味丸或森登-11味散等。⑥飲食調(diào)攝與心理養(yǎng)生等護理要求：飲食宜進易消化,忌油膩食物；起居方面避免過度勞累,不宜久留喧嘩環(huán)境,適當(dāng)參加體育鍛煉；避免生氣、過度悲傷、興奮,鼓勵參與愉悅心身的文體活動等。⑦平均療程：27.18±22.89日。在診治心刺痛病方面,蘇老師以助胃火、促進精濁代謝,強調(diào)赫依與其素并調(diào)的治療原則的正確性以及他發(fā)明的吉如很希莫吉樂和新-Ⅱ號兩個新藥的特殊效果均得到了臨床驗證。繼承人在吸收蘇老師學(xué)術(shù)思想和臨床經(jīng)驗過程中提出了治療心刺痛病的新技術(shù)----蘇老師驗方與心身互動療法結(jié)合治療的方法。3.90名心刺痛病病例療效評價：①臨床癥狀：治療后三組所有癥狀比治療前均有明顯改善(P0.05)。分析各組特點發(fā)現(xiàn),觀察組的胸悶癥狀好轉(zhuǎn)程度更加明顯,蒙藥組的口干、心慌癥狀好轉(zhuǎn)的比較明顯,以上兩組各自的優(yōu)勢癥狀均好于對照組；②心電圖：無明顯差異(P0.05); ③SCL90心理量表：觀察組心理治療療效明顯優(yōu)于蒙藥組和對照組,但組間無差異(P0.05)。三組臨床總有效率分別為觀察組86.7%,蒙藥組80.0%,對照組76.7%,三組之間無差異(P0.05)。4.治療機制：治療前和治療后血清之間差異表達microRNA有34個(P0.05),治療前與正常人血清之間差異表達microRNA有19個(P0.05),而三組血清之間差異表達microRNA有7個(P0.05)。其中Hsa-miRNA-766-3P有相關(guān)研究報道,其他6種尚未找到研究報道。通過對其靶基因的進一步分析發(fā)現(xiàn)了21個候選基因,其中FLT4和ADAM9與血管硬化有關(guān),尤其FLT4對于血管網(wǎng)絡(luò)的發(fā)展和促進內(nèi)皮細(xì)胞的增殖、存活和遷移、并調(diào)控血管生成有關(guān),且是、VEGFC和VEGFD的表面受體。而VEGF與心刺痛病嚴(yán)重程度相關(guān)。以此可以推理Hsa-miRNA-766-3P可能與蘇榮扎布驗方結(jié)合心身互動療法治療心刺痛具有相關(guān)性,但作用機理還需進一步進行深入研究。結(jié)論：①蘇老師學(xué)術(shù)思想中最突出的一點是對蒙醫(yī)整體觀思想提出了自己的新見解,從而豐富和發(fā)展了其理論內(nèi)涵。建立在此思想基礎(chǔ)之上的以尋根治源為根本、以把握赫依的治療為關(guān)鍵點、以促進氣血運行疏通經(jīng)脈為具體步驟、調(diào)解胃火與體素間平衡為目的、重視清除陳熱的治療原則、注重心理作用、心-身-言三業(yè)相結(jié)合、強調(diào)養(yǎng)生保健等臨床診療思維也充分體現(xiàn)了現(xiàn)代醫(yī)學(xué)《生物—心理—社會》醫(yī)學(xué)模式理念。這些學(xué)術(shù)思想對我們臨床實踐中具有很高的指導(dǎo)價值。②蘇老師是一名博學(xué)多識、臨床經(jīng)驗豐富且具有自身獨特思維特點和診療手法技術(shù)的一代蒙醫(yī)大師。除技術(shù)以外他的仁心醫(yī)德是造就他成長為國醫(yī)大師的主要因素所在。在診治心刺痛病方面,蘇老師的以助胃火、促進精濁代謝,強調(diào)赫依與其素并調(diào)的治療原則的正確性以及他發(fā)明的吉如很希莫吉樂和新-Ⅱ號兩個新藥的特殊效果均得到了臨床驗證。③繼承人在吸收蘇老師學(xué)術(shù)思想過程中提出了治療心刺痛病的新技術(shù)----蘇老師驗方與心身互動療法結(jié)合治療方法,在蒙醫(yī)學(xué)整體觀理論基礎(chǔ)上提供了方法上的創(chuàng)新,并有效提高了心刺痛病的治療效果。④治療機制研究發(fā)現(xiàn),Hsa-microRNA-766-3P可能與蘇老師驗方結(jié)合蒙醫(yī)心身互動療法治療心刺痛病治療相關(guān)。這對蒙醫(yī)治病提供了科學(xué)依據(jù)。但是,更深層次的作用機理還需進一步去深入研究和驗證。
[Abstract]:Objective: To summarize and organize the academic thought and clinical experience of Professor Sue Ron Jabu; Study on Su Rong Jabu prescription and psychosomatic therapy clinical curative effect of combined treatment of heart pain disease, and to explore its therapeutic mechanism. The research methods and research contents: 1. through the collation of teacher Su hard life, learning, teaching practice, life and growth experience, perception of these special life experience of teacher's personality formation and become the effect of Chinese medicine master's study and research; teacher Su papers, monographs and literature, analyzing and summarizing the Su teacher academic thought source and its characteristics, based on the traditional Mongolian medicine overall thought and medical model proposed heir own new insights.2. by reading classics teacher Su papers, monographs and related Mongolian as well as tutor clinic study, selected 11 tutors at the treatment of dominant diseases, this Analysis of these tutors on the cause of the disease, symptoms and treatment characteristics and advantages, and select two typical cases to be analyzed from each category of academic thoughts and clinical experience to summarize and sum up the characteristics of teachers. 190 patients had the diagnosis and treatment of heart hurt teacher from the etiology and pathogenesis, disease characteristics, treatment treatment, nursing and medication characteristics, in terms of frequency of use and treatment prescription were analyzed retrospectively. The treatment of heart disease a summary of the teacher's academic thoughts and clinical experience, and put forward the teacher Su prescription combined with.3. new method of psychosomatic therapy in the treatment of heart disease according to the diagnostic criteria of tingling 90 heart disease patients were randomly divided into pain. Su treatment group (Mongolian medicine group) teacher, teacher Su prescription and psychosomatic therapy combined with treatment group (observation group) and Danshen treatment group (control group) three groups, each group of 30, seven days for a course of treatment, a total of The three course of treatment. Through the observation of clinical symptoms, ECG and SCL90 psychological scale and other indicators, the control group in the clinical efficacy of.4. three or above on the basis of clinical studies, the observation group of 6 heart disease patients before treatment and pain after treatment of serum microRNA expression were analyzed to investigate the curative effect and mechanism of 6. Normal human serum samples as control group. The specific operation is to use each extraction 10ml blood, serum separation, extraction of total RNA from serum, gene chip (Microarray) detection, bioinformatics analysis. Results: 1. Su teacher summary of academic thought: the most prominent teacher Su's academic thoughts about the overall view of Mongolian medicine rich and development. Mr. Su in 1980 issued "on the whole view of Mongolian medicine on" as the topic, make him become a modern Mongolian medicine in the field of the research of Mongolian medicine overall thought of Su scholars. The teacher put forward to the theory of yin and Yang based Mongolian holism is the crux of Mongolian medicine theory. Relationship between man and nature, the five line and three correlation, correlation between the three and seven - three of their basic connotation of it. And the three and seven factors related to "jingzhuo the theory is the essence of" metabolism ". To enrich and develop the modern Mongolian medicine holistic theory connotation. The typical academic teacher Su is also reflected in: the roots of governance for the fundamental source: to grasp the key points for the treatment of taking Heiyi; to promote blood circulation to dredge the meridians specific steps: mediation gastropyretic and voxel for the purpose of balance; pay attention to remove Chen heat; pay attention to the psychological effect; mind body language three combination; a total of 9 aspects of health care. The study emphasizes Ganwudao, Mr. Su is a knowledgeable, rich clinical experience and has its own unique Thinking of the characteristics and treatment technology of a generation of Mongolian medicine master. In addition to technology of his infinite compassion and mercy and other life and character, with both a benevolent mind and heart charm also makes him grow into the main factors of Chinese medicine master. In the teacher's guidance, an overview of Mongolian medicine theory, I put forward the whole structure of Mongolian medicine thought: "whole body the unity of body and mind, the unity of man and society, man and nature and the unity of man and the universe (time and space) new insights into the five aspects of the overall unity", and from this understanding further reasoning, thinking of medical model, medical model that Mongolian medicine should be related to "biological - psychological - social - spatial nature (the universe)" clinical experience of new ideas.2. Su five dimensional structure composed of summary: through literature review and learning with the teacher, the teacher Su the most adept at diagnosis and treatment A heart disease, arrhythmia, myocarditis, renal calculi, chronic bronchitis, chronic gastritis, insomnia, mental disorders, epilepsy, irregular menstruation, concept, uterine fibroids and other eleven kinds of causes, symptoms and explain the dialectical treatment were summarized in the Su Lao division of the unique insights and experience of diagnosis and treatment, technique characteristics. The teacher found Su cure four in use, flexible combination, clever dispensing the dialectical characteristics of attractor is more prominent. The teacher Su specializes in the treatment of heart disease. Most were retrospectively studied, summed up the following 7 aspects. The characteristics of pathogenesis and disease type 1: Su teachers believe that the fundamental causes of coronary artery occlusion is jingzhuo poor metabolism, turbidity adhesion to the vessel wall due to the clinical disease; and the element with taking Heiyi type for the majority. The treatment method: mainly to help promote stomach, turbid sperm metabolism, thinning 閫氱粡鑴夋敼鍠勬皵琛，

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