【摘要】：研究背景 銀屑病(Psoriasis),是一種常見而頑固難治的慢性、炎癥性皮膚病。其累及全球約2%的人口,以紅斑鱗屑為主要表現(xiàn),主要病理學(xué)改變是角質(zhì)形成細(xì)胞異常增生、角化過度及角化不全,并有多種炎性細(xì)胞如單核細(xì)胞和淋巴細(xì)胞浸潤。由于病因不清,尚無根治的有效方法,銀屑病給患者和家屬帶來身心雙重傷害。其病機(jī)錯(cuò)綜復(fù)雜,以T淋巴細(xì)胞亞群介導(dǎo)的免疫功能紊亂在銀屑病的發(fā)生和發(fā)展過程中起關(guān)鍵作用,研究證實(shí)Th1/Th2細(xì)胞平衡失調(diào)是銀屑病發(fā)病的重要原因,但近年來研究發(fā)現(xiàn)Th17和Treg兩種不同的T細(xì)胞亞群在銀屑病發(fā)生過程中也起著重要作用。干細(xì)胞(Stem Cell.SC),是人體的起源細(xì)胞,具有自我復(fù)制和多向分化的潛能。依據(jù)細(xì)胞來源與發(fā)育潛能性的不同可以將干細(xì)胞分為成體干細(xì)胞(adult sterm cells,ASC)和胚胎干細(xì)胞(embryonic stem cells,ESC),成體干細(xì)胞是未分化細(xì)胞,存在于一種已經(jīng)分化組織中,具有自我更新而且能夠特化形成組成該類型組織的細(xì)胞。其中,間充質(zhì)干細(xì)胞(mesenchymal stem cell,)是成體干細(xì)胞中的一員,是一種具有多分化潛能的非造血系祖細(xì)胞,起源于中胚層,廣泛存在于骨髓、脂肪、胎盤、臍帶、表皮等組織中,可以分化為多種中胚層來源細(xì)胞譜系,在體外特定誘導(dǎo)條件下.不僅能分化成同胚層的骨骼、脂肪和軟骨細(xì)胞,還能夠跨胚層分化為內(nèi)胚層的神經(jīng)或心肌細(xì)胞等。除具有干細(xì)胞多向分化的潛能外,間充質(zhì)干細(xì)胞還具有特殊的低免疫原性和強(qiáng)有力的免疫調(diào)節(jié)能力,能夠分泌眾多細(xì)胞因子對T淋巴細(xì)胞產(chǎn)生免疫調(diào)節(jié)作用,可以抑制促炎性T淋巴細(xì)胞的活化、增殖和分化成熟以及改變免疫細(xì)胞分泌的細(xì)胞因子,使其傾向于抗炎和免疫耐受功能,也可以促進(jìn)抑制炎癥反應(yīng)的T淋巴細(xì)胞的優(yōu)勢分化,以幫助機(jī)體恢復(fù)免疫平衡。間充質(zhì)細(xì)胞對T淋巴細(xì)胞的免疫抑制作用在古代中醫(yī)學(xué)中并沒有對此類細(xì)胞的論述,但現(xiàn)在許多文獻(xiàn)證明,間充質(zhì)干細(xì)胞在來源、分布和功能上與中醫(yī)上的“腎精”有許多相似相同之處,干細(xì)胞具有腎精的屬性。另外,目前也有相關(guān)研究證實(shí),補(bǔ)腎培元類中藥具有調(diào)節(jié)MSCs生物學(xué)特性的功能,中藥復(fù)方、單味中藥以及中藥有效組分等多種形式都能夠影響干細(xì)胞的生物學(xué)特性及功能�！靶]郁,腎精虧損”是宋坪主任醫(yī)師研究團(tuán)隊(duì)在繼承朱仁康等名老專家學(xué)術(shù)思想,論治銀屑病取得較好臨床療效的基礎(chǔ)上,結(jié)合銀屑病的發(fā)病特點(diǎn),提出的銀屑病的核心病機(jī),并對應(yīng)以開通玄府、補(bǔ)腎培元方法治療,臨床上主要是在麻黃、桂枝等開通玄府藥物基礎(chǔ)上,加仙靈脾、仙茅、威靈仙、補(bǔ)骨脂、桑寄生、杜仲、續(xù)斷、肉蓯蓉等補(bǔ)腎培元類藥物,取得了良好療效,但是其具體的作用機(jī)制目前還不清楚。因此,本課題在深入學(xué)習(xí)傳承導(dǎo)師“開通玄府、補(bǔ)腎培元”治療銀屑病的理論和臨床實(shí)踐經(jīng)驗(yàn),總結(jié)前期工作的基礎(chǔ)上,首次對“開通玄府、補(bǔ)腎培元”治療銀屑病的可能分子機(jī)制提出研究假說,認(rèn)為銀屑病的發(fā)病與T細(xì)胞免疫紊亂密切相關(guān),作為T細(xì)胞免疫網(wǎng)絡(luò)失衡的上游環(huán)節(jié),銀屑病患者M(jìn)SC免疫調(diào)節(jié)功能存在異常,是導(dǎo)致銀屑病發(fā)病的關(guān)鍵,開通玄府、補(bǔ)腎培元法可通過干預(yù)MSC的功能,調(diào)節(jié)外周血Th17和Treg細(xì)胞及分泌的細(xì)胞因子,發(fā)揮治療銀屑病的作用。本研究采用流式細(xì)胞術(shù)、PCR、ELISA等生物信息學(xué)技術(shù),對銀屑病患者和健康人AMSCs在生物學(xué)特性和免疫調(diào)控功能進(jìn)行比較,并進(jìn)一步研究銀屑病患者AMSCs對患者外周血淋巴細(xì)胞的免疫調(diào)控作用,在此基礎(chǔ)上以中藥單體淫羊藿多糖和巴戟天多糖為干預(yù)手段,圍繞單體對AMSCs的生物學(xué)特性和免疫調(diào)控作用探討運(yùn)用“開通玄府、補(bǔ)腎培元”理論指導(dǎo)治療銀屑病臨床療效的分子機(jī)制,驗(yàn)證假說的客觀性,闡釋其理論內(nèi)涵,為今后“開通玄府、補(bǔ)腎培元”法治療銀屑病提供工作基礎(chǔ)。研究目的 1.對比銀屑病患者和健康人來源的脂肪間充質(zhì)干細(xì)胞(adipose mesenchymal stem cells,AMSCs)的一般生物學(xué)特性和免疫調(diào)控功能差異。2.研究兩組細(xì)胞對銀屑病患者外周血淋巴細(xì)胞(peripheral blood lymphocyte,PBL)的免疫調(diào)控作用。3.研究巴戟天多糖和淫羊藿多糖干預(yù)的銀屑病患者AMSCs對患者PBL的免疫調(diào)控的作用,以從側(cè)面揭示“開通玄府、補(bǔ)腎培元”的理論內(nèi)涵。研究方法 1.體外分離培養(yǎng)AMSCs,培養(yǎng)至第3代備用,采用流式細(xì)胞術(shù)對銀屑病患者和健康人AMSCs的細(xì)胞表型和周期進(jìn)行鑒定;采用油紅0和堿性磷酶染色法鑒定兩種AMSCs的成脂、成骨分化能力;用PCR和ELISA的方法檢測銀屑病患者和健康人AMSCs表達(dá)或分泌抑炎或促炎因子情況。2.將銀屑病患者和健康人AMSCs分別加入患者PBL培養(yǎng)體系中,并設(shè)外周血淋巴細(xì)胞單獨(dú)培養(yǎng)對照組,采用流式細(xì)胞術(shù)檢測銀屑病患者PBL中Treg和Th17比例,用PCR和ELISA檢測銀屑病患者PBL表達(dá)或分泌抑炎及促炎因子情況。3.用中藥單體巴戟天多糖和淫羊藿多糖干預(yù)銀屑病患者AMSCs,采用CCK-8實(shí)驗(yàn)篩選藥物干預(yù)濃度,采用流式細(xì)胞術(shù)和成脂、成骨染色檢測中藥干預(yù)后銀屑病患者AMSCs的生物學(xué)特性變化,采用PCR方法檢測中藥干預(yù)后的銀屑病患者AMSCs表達(dá)抑炎和促炎因子情況。進(jìn)一步將藥物干預(yù)后的銀屑病患者AMSCs與銀屑病患者外周血淋巴細(xì)胞共培養(yǎng),并設(shè)健康對照組。采用流式細(xì)胞術(shù)檢測患者PBL中Treg和Th17比例,用PCR和ELISA檢測患者外周血淋巴細(xì)胞表達(dá)或分泌抑炎和促炎因子情況。研究結(jié)果 論文的第一部分,我們發(fā)現(xiàn)健康人和銀屑病患者來源的兩組AMSCs細(xì)胞生長形態(tài)無顯著變化,具有相同的表型,都表達(dá)CD29+,CD44+,CD73+,CD45-,CD31-及HLADR-。而且,都可分化成骨細(xì)胞和成脂細(xì)胞,但銀屑病組AMSCs增殖趨緩(p0.05),與健康對照組相比成脂分化能力較強(qiáng)。另外,銀屑病患者較健康人AMSCs表達(dá)或分泌的抑炎因子IL-10、IDO、TGF-β等下降(IL-10 p0.05,TGF-β p0.01,IDOp0.001),TNF-α,IFN-Y等促炎細(xì)胞因子增強(qiáng)(p0.05)。論文的第二部分,研究發(fā)現(xiàn)與健康人AMSCs+PBL相比,銀屑病患者AMSCs+PBL組中Treg淋巴細(xì)胞數(shù)量減少(p0.01),同時(shí),降低了 Treg淋巴細(xì)胞的核轉(zhuǎn)錄因子Foxp3及PBL中IL-10和TGF-β水平的表達(dá)及分泌(p0.05),但是,銀屑病患者AMSCs對外周血Th17淋巴細(xì)胞比例的改變與健康人AMSCs相比并無明顯影響,對Th17淋巴細(xì)胞的轉(zhuǎn)錄因子RORγt及外周血淋巴細(xì)胞分泌促炎因子的抑制作用具有減弱的趨勢,但結(jié)果無統(tǒng)計(jì)學(xué)差異。說明銀屑病患者AMSCs對抑制炎性細(xì)胞的免疫調(diào)控減弱,而對促炎性細(xì)胞的免疫調(diào)控減弱不明顯。論文的第三部分,通過檢測兩種多糖對AMSCs抑制外周血淋巴細(xì)胞增殖的作用,結(jié)果發(fā)現(xiàn)淫羊藿多糖沒有促進(jìn)銀屑病患者AMSCs抑制外周血淋巴增殖的作用,而巴戟天多糖濃度為28ug/ml、56ug/ml、112ug/ml時(shí),外周血淋巴細(xì)胞受到明顯抑制,其中巴戟天多糖在28ug/ml時(shí)對銀屑病患者AMSCs抑制外周血淋巴細(xì)胞增殖的作用最明顯(P0.001)。選擇MOP在28ug/ml的濃度進(jìn)一步實(shí)驗(yàn)研究。通過研究補(bǔ)腎藥巴戟天多糖在銀屑病患者AMSCs對患者外周血PBMC免疫調(diào)控中的作用,發(fā)現(xiàn)巴戟天多糖對銀屑病患者AMSCs的細(xì)胞表型、周期、成脂及成骨分化能力沒有影響,但是巴戟天多糖能夠增強(qiáng)銀屑病患者AMSCs的免疫抑炎功能,增加抑炎因子TGF-β、IL-10、IDO及抑炎相關(guān)配體PD-L1及受體TLR3的mRNA表達(dá)(IL-10p0.05),同時(shí),能夠減弱銀屑病患者AMSCs的免疫促炎功能,減少促炎因子TNF-α及抑炎相關(guān)受體TLR4 mRNA表達(dá)。將巴戟天多糖干預(yù)后的銀屑病患者AMSCs與PBL共培養(yǎng),與健康人AMSCs+PBL相比,結(jié)果發(fā)現(xiàn),巴戟天多糖能夠促進(jìn)銀屑病AMSCs增加Treg的比例,同時(shí)增加PBL抑炎因子TGF-β和IL-10的表達(dá)或分泌(TGF-β P0.05)。而巴戟天多糖對促進(jìn)銀屑病患者AMSCs下調(diào)Th17淋巴細(xì)胞的比例沒有影響,對減少外周血淋巴細(xì)胞促炎因子IL-17和IL-23的表達(dá)或分泌作用較弱。研究結(jié)論 1.銀屑病患者AMSCs較健康人的增殖和成脂分化能力下降,表達(dá)及分泌抑炎因子的能力明顯減弱。2.銀屑病患者AMSCs促進(jìn)Treg淋巴細(xì)胞增殖的能力較健康人減弱,并且促使外周血淋巴細(xì)胞中FoxP3、IL-10和TGF-β的表達(dá)的能力減弱。3.巴戟天多糖能夠增強(qiáng)銀屑病患者AMSCs的分泌抑炎因子的能力。同時(shí),巴戟天多糖處理后的銀屑病AMSCs對Treg細(xì)胞的促增殖能力增強(qiáng),并且患者AMSCs對外周血淋巴細(xì)胞分泌抑炎因子的能力增強(qiáng),因此,巴戟天多糖具有增強(qiáng)AMSC的抑炎功能的作用。4.研究采用分子生物學(xué)前沿技術(shù)探討了補(bǔ)腎培元中藥單體促進(jìn)銀屑病患者免疫抑炎功能作用,增強(qiáng)AMSCs對外周血免疫調(diào)控的細(xì)胞分子機(jī)制,從一個(gè)側(cè)面闡釋了“開玄補(bǔ)腎”的理論內(nèi)涵。
[Abstract]:Background Psoriasis is a common and refractory chronic, inflammatory skin disease that affects about 2% of the world's population. It is characterized by erythematous scales. The main pathological changes are abnormal proliferation of keratinocytes, hyperkeratosis and incomplete keratosis, and infiltration of many inflammatory cells such as monocytes and lymphocytes. The pathogenesis of psoriasis is complicated. Immune dysfunction mediated by T lymphocyte subsets plays a key role in the occurrence and development of psoriasis. Studies have confirmed that the imbalance of Th1/Th2 cells is an important cause of psoriasis. In recent years, it has been found that two different T cell subsets, Th17 and Treg, play an important role in the pathogenesis of psoriasis. Stem cells (Stem Cell. SC) are human origin cells with the potential of self-replication and multi-differentiation. Ells, ASC, and embryonic stem cells (ESC), adult stem cells are undifferentiated cells, which exist in a differentiated tissue, have self-renewal and can specialize to form the cells that make up this type of tissue. Non-hematopoietic progenitor cells, derived from the mesoderm and widely distributed in bone marrow, fat, placenta, umbilical cord, epidermis and other tissues, can differentiate into a variety of mesoderm-derived cell lineages under specific induction conditions in vitro. They can not only differentiate into homozygotic skeleton, fat and chondrocytes, but also differentiate into endodermal nerves across the embryonic layer. Mesenchymal stem cells (MSCs) have special immunogenicity and strong immunomodulatory ability. They can secrete many cytokines to produce immunomodulatory effects on T lymphocytes. They can inhibit the activation, proliferation, differentiation and maturation of proinflammatory T lymphocytes and change immunity. The cytokines secreted by epidemic cells tend to resist inflammation and immune tolerance, and also promote the dominant differentiation of T lymphocytes that inhibit inflammation in order to help restore the immune balance of the body. It has been proved that mesenchymal stem cells have many similarities with kidney essence in origin, distribution and function, and stem cells have the properties of kidney essence. "Xuanfu depression, kidney essence deficiency" is the core pathogenesis of psoriasis proposed by Song Ping's research team on the basis of inheriting Zhu Renkang's academic ideas and achieving better clinical efficacy in the treatment of psoriasis. To open Xuanfu, invigorate the kidney and peel the yuan method of treatment, mainly in ephedra, Guizhi and other open Xuanfu drugs on the basis of adding Xianling spleen, Xianmao, Wellingxian, psoralea, mulberry parasitic, Eucommia ulmoides, Dipsacus, Cistanche deserticola and other invigorate the kidney and peel the yuan drugs, and achieved good results, but the specific mechanism is still unclear. Based on the theory and clinical practice of "opening Xuanfu and invigorating the kidney and peiyuan" in the treatment of psoriasis, and on the basis of summing up the previous work, a hypothesis was put forward for the first time to study the possible molecular mechanism of "opening Xuanfu and invigorating the kidney and peiyuan" in the treatment of psoriasis. In the upstream link of the disequilibrium of epidemic network, the abnormal immune regulation function of MSC in psoriasis patients is the key to the pathogenesis of psoriasis. Opening Xuanfu and invigorating kidney and Peiyuan can regulate the peripheral blood Th17 and Treg cells and secreted cytokines by interfering with the function of MSC. Flow cytometry, PCR, ELISA were used in this study. The biological characteristics and immune regulation function of AMSCs in psoriatic patients and healthy people were compared by bioinformatics techniques. The immune regulation effect of AMSCs on peripheral blood lymphocytes of patients with psoriasis was further studied. On this basis, the monomer of Herba Epimedii polysaccharides and Morinda officinalis polysaccharides were used as intervention means to surround the monomer on AMS. To explore the biological characteristics and immune regulation function of Cs in the treatment of psoriasis by using the theory of "opening Xuanfu, invigorating kidney and peiyuan" to guide the molecular mechanism of the clinical efficacy of psoriasis, verify the objectivity of the hypothesis, and explain its theoretical connotation, so as to provide a basis for the future treatment of psoriasis by "opening Xuanfu, invigorating kidney and peiyuan". The general biological characteristics and immunoregulatory function of adipose mesenchymal stem cells (AMSCs) from healthy volunteers and healthy volunteers were compared. 2. To study the immunoregulatory effect of AMSCs on peripheral blood lymphocyte (PBL) in patients with psoriasis. 3. To study the intervention of Morinda officinalis polysaccharide and Epimedium polysaccharide. The effect of AMSCs on the immune regulation of PBL in patients with psoriasis was studied in order to reveal the theoretical connotation of "opening Xuanfu, invigorating kidney and nourishing kidney and nourishing kidney and nourishing kidney and nourishing kidney and nourishing kidney and nourishing kidney and nourishing kidney and nourishing kidney". Phosphatase staining was used to identify the adipogenesis and osteogenic differentiation ability of AMSCs. PCR and ELISA were used to detect the expression or secretion of anti-inflammatory or pro-inflammatory factors in AMSCs from psoriatic patients and healthy people. 2. AMSCs from psoriatic patients and healthy people were added into PBL culture system respectively, and peripheral blood lymphocytes were cultured separately as control group. Treg and Th17 in PBL of psoriasis patients were detected by cytometry, and the expression or secretion of anti-inflammatory and pro-inflammatory factors in PBL of psoriasis patients were detected by PCR and ELISA. The biological characteristics of AMSCs in patients with psoriasis were detected by colorimetric assay, and the expression of anti-inflammatory and pro-inflammatory factors in patients with psoriasis were detected by PCR. The ratio of Treg and Th17 in PBL was detected by cytometry, and the expression or secretion of anti-inflammatory and pro-inflammatory factors in peripheral blood lymphocytes were detected by PCR and ELISA. 44 +, CD73 +, CD45 -, CD31 - and HLADR -. Moreover, all of them can differentiate into osteoblasts and adipocytes, but the proliferation of AMSCs in psoriasis group slowed down (p0.05), and the adipogenic differentiation ability was stronger than that in healthy control group. In addition, the expression or secretion of anti-inflammatory factors IL-10, IDO, TGF-beta in psoriasis patients were lower than that in healthy people (IL-10 p0.05, TGF-beta p0.01, IDOp 0.001), T-10. In the second part of the paper, the number of Treg lymphocytes in the AMSCs + PBL group was decreased (p0.01) and the expression and secretion of the nuclear transcription factors Foxp3 and IL-10 and TGF-beta in the Treg lymphocytes were decreased (p0.05) compared with those in the healthy subjects (p0.05). AMSCs in patients with psoriasis had no significant effect on the percentage of Th17 lymphocytes in peripheral blood compared with AMSCs in healthy volunteers. The inhibitory effect of AMSCs on the transcription factor RORgamt of Th17 lymphocytes and the secretion of pro-inflammatory factors from peripheral blood lymphocytes was weakened, but the results showed no statistical difference. Epimedium polysaccharide did not promote the proliferation of peripheral blood lymphocytes in psoriasis patients, but Morinda officinalis polysaccharide concentration was 28ug/ml, 56u. The effect of Morinda officinalis polysaccharide on the proliferation of peripheral blood lymphocytes in psoriasis patients was the most obvious (P 0.001) when the concentration of Morinda officinalis polysaccharide was 28 ug/ml. The concentration of MOP at 28 ug/ml was selected for further experimental study. It was found that Morinda officinalis polysaccharides had no effect on the phenotype, cycle, adipogenesis and osteogenic differentiation of AMSCs in psoriasis patients, but Morinda officinalis polysaccharides could enhance the immunosuppressive function of AMSCs in psoriasis patients, increase the mRNA expression of anti-inflammatory factors TGF-beta, IL-10, IDO and anti-inflammatory ligand PD-L1 and receptor TLR3. The results showed that Morinda officinalis polysaccharide could promote the increase of Treg in AMSCs of psoriasis patients compared with AMSCs+PBL in co-culture with PBL. At the same time, the expression or secretion of PBL anti-inflammatory factors TGF-beta and IL-10 were increased (TGF-beta P 0.05). Morinda officinalis polysaccharides had no effect on promoting the down-regulation of Th17 lymphocyte proportion in patients with psoriasis, but had weak effect on reducing the expression or secretion of IL-17 and IL-23 in peripheral blood lymphocyte. The ability of AMSCs to promote the proliferation of Treg lymphocytes in psoriatic patients was weaker than that in healthy people, and the ability of FoxP3, IL-10 and TGF-beta expression in peripheral blood lymphocytes was weaker. 3. Morinda officinalis polysaccharide could enhance the ability of AMSC in psoriatic patients. Meanwhile, AMSC s from Morinda officinalis after polysaccharide treatment can enhance the proliferation of Treg cells and the ability of AMSC s to secrete anti-inflammatory factors from peripheral blood lymphocytes. Therefore, Morinda officinalis polysaccharides can enhance the anti-inflammatory function of AMSC. 4. Molecular biology frontier technology was used in this study. This paper discusses the effect of Kidney-Tonifying and yuan-tonifying Chinese herbal monomer on the immunosuppressive function of psoriasis patients and the cellular and molecular mechanism of AMSCs on peripheral blood immune regulation.
【學(xué)位授予單位】：中國中醫(yī)科學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R275

【參考文獻(xiàn)】

中國期刊全文數(shù)據(jù)庫 前10條

1 曾亞軍;李玲玲;段行武;張潤田;陳廣山;;與銀屑病相關(guān)的T輔助細(xì)胞研究進(jìn)展[J];中國中西醫(yī)結(jié)合皮膚性病學(xué)雜志;2017年01期

2 李瑞婷;王曉麗;張?jiān)畦?;斑塊型銀屑病中醫(yī)治療研究進(jìn)展[J];中醫(yī)臨床研究;2016年36期

3 黃慶雷;魏曉飛;;間充質(zhì)干細(xì)胞免疫調(diào)節(jié)的可塑性[J];中國科學(xué):生命科學(xué);2016年07期

4 張愛娟;王漢裕;鄺衛(wèi)紅;;間充質(zhì)干細(xì)胞的中醫(yī)理論歸屬探討[J];廣州中醫(yī)藥大學(xué)學(xué)報(bào);2016年02期

5 賈彥如;賈曉玲;侯瑞霞;劉瑞風(fēng);張開明;;銀屑病患者骨髓間充質(zhì)干細(xì)胞基因表達(dá)及生物學(xué)特性研究[J];山西醫(yī)藥雜志;2016年01期

6 范瑛;莊晨;宋坪;;基于干細(xì)胞探討開通玄府、補(bǔ)腎培元法治療銀屑病[J];北京中醫(yī)藥;2015年04期

7 曲學(xué)彬;劉星霞;韓晶晶;姚瑞芹;趙春華;;骨髓間充質(zhì)干細(xì)胞抑制CD4~+初始T細(xì)胞體外分化為Th17細(xì)胞[J];基礎(chǔ)醫(yī)學(xué)與臨床;2014年09期

8 劉玉磊;楊東生;;銀屑病患者皮膚間充質(zhì)干細(xì)胞中表皮生長因子、轉(zhuǎn)化生長因子-β1的表達(dá)水平及其意義[J];實(shí)用臨床醫(yī)藥雜志;2014年16期

9 吳志奎;張新華;方素萍;王文娟;王蕾;李敏;王榮新;劉詠梅;柴立民;張沖;劉莉;程艷玲;褚娜利;;基于“腎生髓、髓生血”理論治療地中海貧血[J];世界中醫(yī)藥;2014年06期

10 賈友冀;王晶;孫悅禮;王洪伸;姚敏;趙東峰;李曉峰;楊燕萍;舒冰;唐德志;崔學(xué)軍;李晨光;梁倩倩;卞琴;王成龍;施杞;王擁軍;;中醫(yī)“腎髓系統(tǒng)”芻議[J];世界中醫(yī)藥;2014年06期

中國碩士學(xué)位論文全文數(shù)據(jù)庫 前1條

1 莊晨;宋坪主任醫(yī)師運(yùn)用“開通玄府、補(bǔ)腎培元”法治療銀屑病經(jīng)驗(yàn)總結(jié)及機(jī)理初探[D];北京中醫(yī)藥大學(xué);2015年

，

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