【摘要】：研究目的：當前骨重塑失偶聯(lián)性骨病的藥物治療,通常采用單純抑制骨吸收或刺激骨形成的療法,但多年嘗試而效果不盡人意。原因是單方面抑制骨吸收會阻礙骨形成,同理,單方面刺激骨形成也會伴隨骨吸收增強。說明人為地單一干擾或影響骨重塑的破骨或成骨過程,會破壞骨重塑偶聯(lián)的平衡機制。所以,晚近學界提出“協(xié)同”(synergetic)概念,呼吁應致力開發(fā)能夠重建骨重塑偶聯(lián)平衡的新型治療措施。本研究以全國第五批名老中醫(yī)專家王鴻度教授倡導的“少陽主骨”理論為核心,追溯和整理王鴻度老師“少陽主骨”學說及其運用“和解少陽”法治療“骨繇癥”(骨重塑失偶聯(lián)性骨病,如骨質疏松)的學術思想和臨床經(jīng)驗,為骨重塑失偶聯(lián)性骨病提供新的治療方案和理論依據(jù)。研究方法：1.跟師學習：跟師臨證,持之以恒,細心體察老師對望、聞、問、切的運用,認真仔細做好學習筆記；診后反復思考,撰寫學習心得、體會,總結病案,思考老師的辨證思路與用藥依據(jù)。2.研讀老師的論著：認真仔細研究學習老師已發(fā)表的論著,將論著中的學術觀點與跟師臨證所得結合,讓理論和實踐緊密結合,倘有疑惑,則問之于師,以能更深層次體會老師的學術思想。3.學習老師學術理論淵源相關書目：精讀老師所列書目,追溯老師學術理論淵源,知其然更要知其所然,以期更全面理解老師的學術理論。4.學以致用：將老師的學術理論結合臨床實際靈活運用于臨床,參與老師的自然科學基金項目的實驗工作,并在老師前期研究的基礎上,以隨機對照的方式,選用敏感的骨吸收和骨形成指標及其它相關指標開展臨床實驗,以臨床研究的形式反饋于理論,實現(xiàn)理論——臨床——理論的過程。研究內容：1.王鴻度教授發(fā)掘“少陽主骨”理論的學術思想淵源及“骨繇癥”(骨重塑失偶聯(lián)性骨病,最常見骨質疏松)的研究進展王鴻度老師長于將經(jīng)絡辨證、八綱辨證及臟腑辨證融于一爐,運用針灸和中藥綜合治療骨骼肌肉關節(jié)疾病。老師倡導的“少陽主骨”學術思想源于《黃帝內經(jīng)》,通過梳理該學說散在于各篇的經(jīng)文,匯集歷代知名注家觀點,對其進行了系統(tǒng)整理和研究,汲取現(xiàn)代醫(yī)學對骨生物學及骨病的最新成果,在驗證學術觀點、闡釋病理生理學機制以及臨床實踐中,將二者巧妙地結合起來,形成其獨特的骨病治療和研究的思想與方法,并通過包括國家自然科學基金項目在內的一系列科研課題,從動物實驗到臨床研究,客觀完整揭示其神秘內涵,使之復歸現(xiàn)實臨床,還原其理論地位和使用價值。上世紀九十年代,國際骨生物學界對骨重塑的破骨細胞和成骨細胞的偶聯(lián)過程獲得突破性進展。如果骨重塑失偶聯(lián)(decoupled),其平衡失和調,就演變?yōu)槎喾N代謝性骨病共同的病理基礎。如癌性溶骨性損害、類風濕關節(jié)炎、骨質疏松癥等,均是破骨細胞功能異常活躍而相對成骨細胞功能不足所致；而強直性脊柱炎、牛皮癬性關節(jié)炎、糖尿病夏科氏關節(jié)病等,還有家族基因缺陷的常染色體隱性遺傳病,如硬化性狹窄(sclerosteosis)及范布切姆病(Van Buchen disease),卻是由于成骨能力超過了破骨能力。多年來藥物治療上述某些骨病,只能采用單純抑制骨吸收或刺激骨形成的療法。但因單方面抑制骨吸收會阻礙骨形成：而單方面刺激骨形成也會伴隨骨吸收增強,故效果均不盡人意。以骨質疏松癥為例：二膦酸類雖能有效抑制骨吸收、增加骨量,但骨折率并未降低：長療程更引起衰弱易碎的骨生成,不僅使骨折修復困難,而且抵抗骨合成代謝藥物；若使用骨合成代謝藥物,如甲狀旁腺素(PHT),持續(xù)使用既增強骨形成同時也增強骨吸收且占優(yōu)勢,結果仍然骨量丟失。所以,晚近學術界提出“協(xié)同”(synergetic)概念,呼吁應致力開發(fā)能夠重建骨重塑偶聯(lián)平衡的新型治療措施。中醫(yī)治療各種骨病,強調“腎主骨”,所以無論中醫(yī)方藥或針灸治療各種骨病幾乎都從此立意。而動物和人體實驗也顯示其有抑制骨吸收的效應,又有研究涉及成骨細胞功能,但多數(shù)從一些細胞因子對OB單方面影響入手,而未涉及平衡骨重塑相偶聯(lián)的復雜功能。2.王鴻度教授“少陽主骨”理論學術思想及臨床經(jīng)驗整理與研究王鴻度教授從《黃帝內經(jīng)》“少陽主骨”出發(fā),發(fā)掘并驗證少陽經(jīng)穴與全身骨骼系統(tǒng)的骨強度的病理生理聯(lián)系,闡明其機理是“和調”骨重塑過程的平衡,即《內經(jīng)》“少陽為樞”的觀點；提出少陽主骨所生病者即“骨繇癥”的臨床特征之骨痛,應是多部位的且具有普周性的特點；深入闡述了少陽經(jīng)與骨骼系統(tǒng)之間的生理、病理聯(lián)系、“少陽主骨”與“腎主骨”的關系及少陽“終”“折”之“骨繇癥”在真實世界客觀存在的情況。梳理“少陽主骨”學說的歷史浮沉、厘清其生理病理內涵和意義、以及臨床對應的疾病原型等,構建出相應的理論驗證模型,將湮沒千年的“少陽主骨”學說引入現(xiàn)代科學研究領域；并選擇適當動物模型和實驗室指標,以“和解少陽”為大法,設計了相關的電針足少陽經(jīng)穴和以經(jīng)典“小柴胡湯”為主方的基礎和臨床實驗,選擇多種機能和形態(tài)學指標,證明電針足少陽和小柴胡湯的相關干預對大鼠骨重塑的影響；證明少陽經(jīng)晝夜節(jié)律與骨重塑過程有關。建立以“和解少陽”為主要治療措施的骨病治療新模式,并將臨床治療范圍拓展到原發(fā)性骨質疏松癥、骨平衡紊亂性膝骨關節(jié)炎,以及氟性骨關節(jié)炎等。形成以“和解少陽”為大法,內治與外治結合、中藥與針灸并用,綜合治療骨重塑失偶聯(lián)性骨病的新局面。3.“和解少陽”法對膝骨性關節(jié)炎合并骨質疏松癥的臨床研究本研究以王鴻度老師所倡導的“少陽主骨”學說為指導,從臨床實驗的角度呼應“陰陽自和”、“和為圣度”及“少陽為樞”的觀點,采用Lysholm膝關節(jié)評分系統(tǒng)和WOMAC評分系統(tǒng)結合骨代謝生化指標(BALP、BGP、TRACP、IL-1及TNF-a等),進一步驗證“少陽主骨”的機理是“和調”骨重塑過程的觀點。結論：1.在中醫(yī)學術界,“少陽主骨”學說一直是千古謎題,王鴻度老師論證“復活”《內經(jīng)》的“少陽主骨”學說,匯聚歷代注家還原“少陽主骨”其本來面目,在理論層次上將足少陽經(jīng)的功能與骨骼的生理、病理、治則及治療方案等緊密結合,并系統(tǒng)化,從而構建和推演出有別于以臟象為中心的“腎主骨”理論的“少陽主骨”學說。2.以科學實驗對“少陽主骨”學說進行謹嚴的驗證,并在臨床應用上初步闡明其機理；提出與之對應的“骨繇癥”,在臨床表現(xiàn)上跟現(xiàn)代醫(yī)學所謂“骨重塑失偶聯(lián)性骨病”極為類似,擴展其適應病種。這些研究工作,拓展了足少陽經(jīng)及其經(jīng)穴特性和用途的新知識,豐富了中醫(yī)基礎理論、骨生理病理等內容。3.根據(jù)“陰陽自和”、“和為圣度”及“少陽為樞”的觀點,結合足少陽經(jīng)穴以及“和解少陽”的小柴胡湯對骨重塑失偶聯(lián)性骨病的實驗研究,提出“少陽主骨”的機理是“和調”骨重塑過程。該“和調”機制,為骨質疏松、糖尿病足及癌瘤溶骨損害等多種骨重塑失偶聯(lián)性骨病(骨繇癥)提供新型“協(xié)同”防治方法。4.臨床研究表明,以“少陽主骨”為指導,著眼于“和調”,可以調節(jié)骨重塑偶聯(lián),調其陰陽,損有余補不足,重新構建骨吸收與骨形成的動態(tài)平衡,這有利于解決目前單純使用抗骨吸收劑或促骨合成劑所面臨的困局,為今后多種骨病的中醫(yī)針灸及藥物治療開拓一條新途徑。
[Abstract]:OBJECTIVE: Current therapies for bone remodeling uncoupled osteopathy are usually based solely on inhibition of bone resorption or stimulation of bone formation, but they have been tried for many years with unsatisfactory results. The reason is that unilateral inhibition of bone resorption can hinder bone formation. Similarly, unilateral stimulation of bone formation can accompany enhanced bone resorption. In recent years, the concept of "synergetic" has been put forward, which calls for the development of new therapeutic measures to rebuild the coupling balance of bone remodeling. With the theory of bone as the core, this paper traces back and sorts out Mr. Wang Hongdu's theory of "Shaoyang dominates bone" and his academic thought and clinical experience in the treatment of "osteoporosis" (bone remodeling uncoupled osteopathy, such as osteoporosis) with the method of "reconciling Shaoyang" so as to provide a new treatment plan and theoretical basis for bone remodeling uncoupled osteopathy. Learning: follow the teacher, persevere, carefully observe the teacher's observation, smell, ask, cut the use of careful and careful study notes; after the diagnosis of repeated thinking, write learning experience, experience, summarize medical records, thinking about the teacher's dialectical thinking and medication basis. 2. Read the teacher's works: seriously and carefully study the teacher's published works, will be on the book. The combination of academic viewpoints with the teacher's clinical experience makes the theory and practice closely integrated. If in doubt, ask the teacher for a deeper understanding of the teacher's academic thinking. Understanding the teacher's academic theory. Research Contents: 1. Professor Wang Hongdu excavates the academic thought origin of the theory of "Shaoyang Main Bone" and the research progress of "osteoporosis" (bone remodeling uncoupling osteopathy, the most common osteoporosis) Professor Wang Hongdu is good at differentiating meridians and collaterals. The academic thought of "Shaoyang Zhugu" advocated by the teacher originated from the Yellow Emperor's Internal Classic. Through sorting out the texts scattered in various chapters, the author collected the views of famous annotators of past dynasties, systematically collated and studied them, and drew on modern medicine. The latest achievements in osteobiology and osteopathy have been cleverly combined in verifying academic viewpoints, elucidating pathophysiological mechanisms and clinical practice to form their unique ideas and methods for the treatment and research of osteopathy. Through a series of scientific research projects including the National Natural Science Foundation of China, they have ranged from animal experiments to clinical trials. In the 1990s, the international osteobiology community made a breakthrough in the coupling process of osteoclasts and osteoblasts in bone remodeling. If bone remodeling is decoupled, its imbalance will become more and more. The common pathological basis of various metabolic osteopathy, such as carcinolytic lesion, rheumatoid arthritis, osteoporosis, etc., is the abnormal activity of osteoclasts and the relative inadequacy of osteoblast function; while ankylosing spondylitis, psoriatic arthritis, diabetic Charcot's arthropathy, and other family genetic defects of autosomal recessive Sexually transmitted diseases, such as sclerosteosis and Van Buchen disease, are due to osteogenesis that exceeds osteoclasts. For many years, drugs have been used to treat some of these diseases by simply inhibiting bone resorption or stimulating bone formation. Osteoporosis, for example, can effectively inhibit bone resorption and increase bone mass, but the fracture rate does not decrease: long-term treatment causes weakened and fragile bone formation, which not only makes fracture repair difficult, but also resists bone synthesis and metabolism drugs; if bone synthesis is used Metabolic drugs, such as parathyroid hormone (PHT), continue to be used to enhance bone formation and bone resorption, and as a result, bone mass is still lost. Animal and human experiments also show that it has the effect of inhibiting bone resorption, and some studies involve osteoblast function, but most of them start from the unilateral effect of some cytokines on OB, and do not involve the complex function of balanced bone remodeling coupling. Professor Wang Hongdu's academic thought and clinical experience on the theory of "Shaoyang is the main bone" are summarized and studied. Professor Wang Hongdu explores and verifies the pathophysiological relationship between the points of Shaoyang meridian and the bone strength of the whole skeletal system from the point of "Huangdi Neijing", "Shaoyang is the main bone", and clarifies that the mechanism is the balance of the process of bone remodeling, that is, the "Neijing", "Shaoyang is the main bone." It is pointed out that the clinical characteristics of ostealgia caused by Shaoyang's dominant bone should be multi-site and universal; the physiological and pathological relationship between Shaoyang's meridian and skeletal system, the relationship between Shaoyang's dominant bone and kidney's dominant bone, and the ostealgia caused by Shaoyang's "terminal" and "fracture" are expounded in depth. In the real world, this paper combs the historical ups and downs of the theory of Shaoyang's main bone, clarifies its physiological and pathological connotation and significance, as well as the corresponding clinical disease prototype and so on, constructs the corresponding theoretical verification model, and introduces the theory of Shaoyang's main bone which has been annihilated for thousands of years into the field of modern scientific research; and selects the appropriate animal model and the appropriate animal model. Laboratory indicators, with "reconciliation of Shaoyang" as the major method, designed the relevant electro-acupuncture points of the Foot Shaoyang meridian and the classic "Xiaochaihu Decoction" as the main basic and clinical experiments, select a variety of functional and morphological indicators, prove that electro-acupuncture foot Shaoyang and Xiaochaihu Decoction related intervention on bone remodeling in rats; prove that the Shaoyang meridian circadian rhythm and night. Establish a new model of bone disease treatment with "reconciling Shaoyang" as the main treatment, and expand the scope of clinical treatment to primary osteoporosis, disordered bone balance knee osteoarthritis, and osteoarthritis fluoride, etc. The clinical research of "reconciling Shaoyang" method on knee osteoarthritis with osteoporosis guided by the theory of "Shaoyang is the main bone" advocated by Professor Wang Hongdu, echoes the viewpoints of "Yin and Yang are harmonious", "harmony is holy" and "Shaoyang is the center" from the perspective of clinical experiment. The Lysholm knee scoring system and WOMAC scoring system were combined with bone metabolism biochemical indexes (BALP, BGP, TRACP, IL-1 and TNF-a) to further validate the viewpoint that the mechanism of Shaoyang bone is to "reconcile" the process of bone remodeling. The theory of "Shaoyang Ruling Bone" in "Resurrection" and "Neijing" brings together the annotators of the past dynasties to restore the true nature of "Shaoyang Ruling Bone" and integrates the function of the Foot-Shaoyang meridian with the physiology, pathology, treatment principles and treatment plan of the bones on the theoretical level, so as to construct and deduce the theory of "kidney Ruling Bone" which is different from the theory of "kidney Ruling Bone" centering on viscera-image. The theory of "Shaoyang dominates the bone" is rigorously verified by scientific experiments and its mechanism is preliminarily clarified in clinical application. The corresponding "osteoporosis" is proposed, which is very similar to the so-called "bone remodeling uncoupling osteopathy" in clinical manifestation and expands its adaptability. The new knowledge of the characteristics and uses of the Foot-Shaoyang meridian and its meridians and points has enriched the basic theory of traditional Chinese medicine and bone physiology and pathology. The mechanism of "Shaoyang Zhugu" is "regulating" bone remodeling process. This "regulating" mechanism provides a new "synergistic" prevention and treatment method for osteoporosis, diabetic foot and osteolytic lesion caused by cancer. Reconstructing the dynamic balance between bone resorption and bone formation by remodeling and coupling the joint bones, adjusting its Yin and yang, damaging the excess and compensating the deficiency, is beneficial to solve the predicament faced by the simple use of anti-bone resorption agents or bone-promoting synthesizers at present, and opens up a new way for acupuncture and medicine treatment of various bone diseases in the future.
【學位授予單位】：成都中醫(yī)藥大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R249;R274

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