【摘要】：研究目的：當(dāng)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(huì)阻礙骨形成,同理,單方面刺激骨形成也會(huì)伴隨骨吸收增強(qiáng)。說(shuō)明人為地單一干擾或影響骨重塑的破骨或成骨過(guò)程,會(huì)破壞骨重塑偶聯(lián)的平衡機(jī)制。所以,晚近學(xué)界提出“協(xié)同”(synergetic)概念,呼吁應(yīng)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(guó)第五批名老中醫(yī)專家王鴻度教授倡導(dǎo)的“少陽(yáng)主骨”理論為核心,追溯和整理王鴻度老師“少陽(yáng)主骨”學(xué)說(shuō)及其運(yùn)用“和解少陽(yáng)”法治療“骨繇癥”(骨重塑失偶聯(lián)性骨病,如骨質(zhì)疏松)的學(xué)術(shù)思想和臨床經(jīng)驗(yàn),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(xué)習(xí)：跟師臨證,持之以恒,細(xì)心體察老師對(duì)望、聞、問、切的運(yùn)用,認(rèn)真仔細(xì)做好學(xué)習(xí)筆記；診后反復(fù)思考,撰寫學(xué)習(xí)心得、體會(huì),總結(jié)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(rèn)真仔細(xì)研究學(xué)習(xí)老師已發(fā)表的論著,將論著中的學(xué)術(shù)觀點(diǎn)與跟師臨證所得結(jié)合,讓理論和實(shí)踐緊密結(jié)合,倘有疑惑,則問之于師,以能更深層次體會(huì)老師的學(xué)術(shù)思想。3.學(xué)習(xí)老師學(xué)術(shù)理論淵源相關(guān)書目：精讀老師所列書目,追溯老師學(xué)術(shù)理論淵源,知其然更要知其所然,以期更全面理解老師的學(xué)術(shù)理論。4.學(xué)以致用：將老師的學(xué)術(shù)理論結(jié)合臨床實(shí)際靈活運(yùn)用于臨床,參與老師的自然科學(xué)基金項(xiàng)目的實(shí)驗(yàn)工作,并在老師前期研究的基礎(chǔ)上,以隨機(jī)對(duì)照的方式,選用敏感的骨吸收和骨形成指標(biāo)及其它相關(guān)指標(biāo)開展臨床實(shí)驗(yàn),以臨床研究的形式反饋于理論,實(shí)現(xiàn)理論——臨床——理論的過(guò)程。研究?jī)?nèi)容：1.王鴻度教授發(fā)掘“少陽(yáng)主骨”理論的學(xué)術(shù)思想淵源及“骨繇癥”(骨重塑失偶聯(lián)性骨病,最常見骨質(zhì)疏松)的研究進(jìn)展王鴻度老師長(zhǎng)于將經(jīng)絡(luò)辨證、八綱辨證及臟腑辨證融于一爐,運(yùn)用針灸和中藥綜合治療骨骼肌肉關(guān)節(jié)疾病。老師倡導(dǎo)的“少陽(yáng)主骨”學(xué)術(shù)思想源于《黃帝內(nèi)經(jīng)》,通過(guò)梳理該學(xué)說(shuō)散在于各篇的經(jīng)文,匯集歷代知名注家觀點(diǎn),對(duì)其進(jìn)行了系統(tǒng)整理和研究,汲取現(xiàn)代醫(yī)學(xué)對(duì)骨生物學(xué)及骨病的最新成果,在驗(yàn)證學(xué)術(shù)觀點(diǎn)、闡釋病理生理學(xué)機(jī)制以及臨床實(shí)踐中,將二者巧妙地結(jié)合起來(lái),形成其獨(dú)特的骨病治療和研究的思想與方法,并通過(guò)包括國(guó)家自然科學(xué)基金項(xiàng)目在內(nèi)的一系列科研課題,從動(dòng)物實(shí)驗(yàn)到臨床研究,客觀完整揭示其神秘內(nèi)涵,使之復(fù)歸現(xiàn)實(shí)臨床,還原其理論地位和使用價(jià)值。上世紀(jì)九十年代,國(guó)際骨生物學(xué)界對(duì)骨重塑的破骨細(xì)胞和成骨細(xì)胞的偶聯(lián)過(guò)程獲得突破性進(jìn)展。如果骨重塑失偶聯(lián)(decoupled),其平衡失和調(diào),就演變?yōu)槎喾N代謝性骨病共同的病理基礎(chǔ)。如癌性溶骨性損害、類風(fēng)濕關(guān)節(jié)炎、骨質(zhì)疏松癥等,均是破骨細(xì)胞功能異常活躍而相對(duì)成骨細(xì)胞功能不足所致；而強(qiáng)直性脊柱炎、牛皮癬性關(guān)節(jié)炎、糖尿病夏科氏關(guān)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(guò)了破骨能力。多年來(lái)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(huì)阻礙骨形成：而單方面刺激骨形成也會(huì)伴隨骨吸收增強(qiáng),故效果均不盡人意。以骨質(zhì)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(zhǎng)療程更引起衰弱易碎的骨生成,不僅使骨折修復(fù)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(qiáng)骨形成同時(shí)也增強(qiáng)骨吸收且占優(yōu)勢(shì),結(jié)果仍然骨量丟失。所以,晚近學(xué)術(shù)界提出“協(xié)同”(synergetic)概念,呼吁應(yīng)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(qiáng)調(diào)“腎主骨”,所以無(wú)論中醫(yī)方藥或針灸治療各種骨病幾乎都從此立意。而動(dòng)物和人體實(shí)驗(yàn)也顯示其有抑制骨吸收的效應(yīng),又有研究涉及成骨細(xì)胞功能,但多數(shù)從一些細(xì)胞因子對(duì)OB單方面影響入手,而未涉及平衡骨重塑相偶聯(lián)的復(fù)雜功能。2.王鴻度教授“少陽(yáng)主骨”理論學(xué)術(shù)思想及臨床經(jīng)驗(yàn)整理與研究王鴻度教授從《黃帝內(nèi)經(jīng)》“少陽(yáng)主骨”出發(fā),發(fā)掘并驗(yàn)證少陽(yáng)經(jīng)穴與全身骨骼系統(tǒng)的骨強(qiáng)度的病理生理聯(lián)系,闡明其機(jī)理是“和調(diào)”骨重塑過(guò)程的平衡,即《內(nèi)經(jīng)》“少陽(yáng)為樞”的觀點(diǎn)；提出少陽(yáng)主骨所生病者即“骨繇癥”的臨床特征之骨痛,應(yīng)是多部位的且具有普周性的特點(diǎn)；深入闡述了少陽(yáng)經(jīng)與骨骼系統(tǒng)之間的生理、病理聯(lián)系、“少陽(yáng)主骨”與“腎主骨”的關(guān)系及少陽(yáng)“終”“折”之“骨繇癥”在真實(shí)世界客觀存在的情況。梳理“少陽(yáng)主骨”學(xué)說(shuō)的歷史浮沉、厘清其生理病理內(nèi)涵和意義、以及臨床對(duì)應(yīng)的疾病原型等,構(gòu)建出相應(yīng)的理論驗(yàn)證模型,將湮沒千年的“少陽(yáng)主骨”學(xué)說(shuō)引入現(xiàn)代科學(xué)研究領(lǐng)域；并選擇適當(dāng)動(dòng)物模型和實(shí)驗(yàn)室指標(biāo),以“和解少陽(yáng)”為大法,設(shè)計(jì)了相關(guān)的電針足少陽(yáng)經(jīng)穴和以經(jīng)典“小柴胡湯”為主方的基礎(chǔ)和臨床實(shí)驗(yàn),選擇多種機(jī)能和形態(tài)學(xué)指標(biāo),證明電針足少陽(yáng)和小柴胡湯的相關(guān)干預(yù)對(duì)大鼠骨重塑的影響；證明少陽(yáng)經(jīng)晝夜節(jié)律與骨重塑過(guò)程有關(guān)。建立以“和解少陽(yáng)”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(zhì)疏松癥、骨平衡紊亂性膝骨關(guān)節(jié)炎,以及氟性骨關(guān)節(jié)炎等。形成以“和解少陽(yáng)”為大法,內(nèi)治與外治結(jié)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(yáng)”法對(duì)膝骨性關(guān)節(jié)炎合并骨質(zhì)疏松癥的臨床研究本研究以王鴻度老師所倡導(dǎo)的“少陽(yáng)主骨”學(xué)說(shuō)為指導(dǎo),從臨床實(shí)驗(yàn)的角度呼應(yīng)“陰陽(yáng)自和”、“和為圣度”及“少陽(yáng)為樞”的觀點(diǎn),采用Lysholm膝關(guān)節(jié)評(píng)分系統(tǒng)和WOMAC評(píng)分系統(tǒng)結(jié)合骨代謝生化指標(biāo)(BALP、BGP、TRACP、IL-1及TNF-a等),進(jìn)一步驗(yàn)證“少陽(yáng)主骨”的機(jī)理是“和調(diào)”骨重塑過(guò)程的觀點(diǎn)。結(jié)論：1.在中醫(yī)學(xué)術(shù)界,“少陽(yáng)主骨”學(xué)說(shuō)一直是千古謎題,王鴻度老師論證“復(fù)活”《內(nèi)經(jīng)》的“少陽(yáng)主骨”學(xué)說(shuō),匯聚歷代注家還原“少陽(yáng)主骨”其本來(lái)面目,在理論層次上將足少陽(yáng)經(jīng)的功能與骨骼的生理、病理、治則及治療方案等緊密結(jié)合,并系統(tǒng)化,從而構(gòu)建和推演出有別于以臟象為中心的“腎主骨”理論的“少陽(yáng)主骨”學(xué)說(shuō)。2.以科學(xué)實(shí)驗(yàn)對(duì)“少陽(yáng)主骨”學(xué)說(shuō)進(jìn)行謹(jǐn)嚴(yán)的驗(yàn)證,并在臨床應(yīng)用上初步闡明其機(jī)理；提出與之對(duì)應(yīng)的“骨繇癥”,在臨床表現(xiàn)上跟現(xiàn)代醫(yī)學(xué)所謂“骨重塑失偶聯(lián)性骨病”極為類似,擴(kuò)展其適應(yīng)病種。這些研究工作,拓展了足少陽(yáng)經(jīng)及其經(jīng)穴特性和用途的新知識(shí),豐富了中醫(yī)基礎(chǔ)理論、骨生理病理等內(nèi)容。3.根據(jù)“陰陽(yáng)自和”、“和為圣度”及“少陽(yáng)為樞”的觀點(diǎn),結(jié)合足少陽(yáng)經(jīng)穴以及“和解少陽(yáng)”的小柴胡湯對(duì)骨重塑失偶聯(lián)性骨病的實(shí)驗(yàn)研究,提出“少陽(yáng)主骨”的機(jī)理是“和調(diào)”骨重塑過(guò)程。該“和調(diào)”機(jī)制,為骨質(zhì)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(yáng)主骨”為指導(dǎo),著眼于“和調(diào)”,可以調(diào)節(jié)骨重塑偶聯(lián),調(diào)其陰陽(yáng),損有余補(bǔ)不足,重新構(gòu)建骨吸收與骨形成的動(dòng)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(xué)位授予單位】：成都中醫(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;R274

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