녹용약침(鹿茸藥鍼)이 CIA 모델 생쥐의 염증인자 생성억제에 미치는 영향

황종순,황지혜,이현진,이동건,강민주,백성욱,조현석,김경호,김갑성,Hwang, Jong-Soon,Hwang, Ji-Hye,Lee, Hyun-Jin,Lee, Dong-Gun,Kang, Min-Joo,Back, Song-Ook,Cho, Hyun-Seok,Kim, Kyung-Ho,Kim, Kap-Sung 대한침구의학회 2007 대한침구의학회지 Vol.24 No.6

Backgrounds : Rheumatoid Arthritis(RA) is known as the chronic inflammatory diseasethat induces persistent inflammation in the joint cavity. The destruction of cartilage occurs as the result of bones destoyed by pannus, several influential cytokines induced by the synovial capsulitis, varieties of proteinases, $O_2$ radicals, and the secondary degenerative changes of articular cartilage. The type 2 collagen-induced arthritis model is used in recent experimental research on rheumatoid arthritis. Cervus elaphus sibiricus (Nockyong) has the effect of relieving pain by nourishing the muscles, joints, and bones. It is also known to be efficacious in promoting and enhancing the immune system. The objective of this study was to investigate the effect of Cervus elaphus sibiricus herbal acupuncture to inhibit the generation of proinflammatory enzyme on type 2 collagen-induced arthritis. I investigated the inhibition of mRNA transcription of MIF(macrophage migration inhibitory factor), $TNF-{\alpha}$(Tumor necrosis $factor-{\alpha}$) and MMP-9 (matrix metalloproteinase-9) of Cervus elaphus sibiricus herbal acupuncture using an in vitro test. Also investigated was the inhibition of differentiation of Th 1 cells and activation of cytokines(MIF, $TNF-{\alpha}$, IL-6, MMP-9), which are known to cause initial RA ,and are also related to the morphology of the synovial membranes of the joint capsule, by an in vivo test, using CIA(collagen induced arthritis) model mice. Materials & methods : The laboratory animals used in this experiment were 4 week-old DBA female mice, weighing approximately 20 grams, and adjusted to the laboratory environment. The experiment was divided into the normal group(NOR)-no treated group, control group(CON)-CIA induced group, and sample group(SAM)-Cervus elaphus sibiricus herbal acupuncture treated group. RA was induced in the mice via injection of $50{\mu}{\ell}$ C II mixed CFA. The Cervus elaphus sibiricus herbal acupuncture solution was applied on $GB_{35}$(陽陵泉) for 26 days from the 3rd day of RA inducement. The concentration of the solution was determined via a MTT assay. To research the effect on the expression of MIF, $TNF-{\alpha}$ and MMP-9 mRNA, RT-PCR was performed on synovial membrane cells from the knee joint of CIA mice. C II induced RA knee joint's histo-chemical synovial membrane was observed using a specimen model via the Hematoxilin and Eosin dying technique. Results : The expression of mRNA of RA-related cytokines such as MIF, $TNF-{\alpha}$, and MMP-9 dosedependently decreased in the cell from the synovial membranes of the joint, which is treated with Cervus elaphus sibiricus herbal acupuncture solution. In mice treated with Cervus elaphus sibiricusherbal acupuncture, the damage of synovial membranes of the joint was lessened, and differentiation of Th 1 cells was suppressed. The activation of RA-related cytokines such as MIF was suppressed, and the generation of $TNF-{\alpha}$ and MMP-9 showed a statistically significant decreas. Conclusions : It is speculated that Cervus elaphus sibiricus herbal acupuncture has the therapeutic effect of palliating the damage of the tissue impaired by RA by inhibition of the initial RA progression and by regulating excessive differentiation of Th 1 cell as it suppresses the generation of RA-related cytokines during the highest stage of RA by acting on pro-inflammatory enzymes.

足三里 桑枝藥鍼이 Collagen-induced arthritis에 미치는 영향

정영돈,임윤경,이현진 대한침구의학회 2006 대한침구의학회지 Vol.23 No.6

Objectives : The purpose of this study is to observe the effects of Mori Ramulus herbal-acupuncture solution(MR-HAS) on arthritis of mice induced by Collagen Ⅱ at Joksamni(St36). Methods : The author performed several experimental items. First, it is the cell survival rate of mice lung fibroblasts. Second, it is the incidence rate of arthritis and arthritis index of CIA. Third, it is the levels of IL-6, TNF-α, IFN-γ, IL-1β, IgG, IgM and anti-collagen Ⅱ in serum and the level of IFN-γ, IFN-γ/IL-4 ratio in CIA mouse spleen cell culture. Fourth, it is histological analysis of the mice joint. Fifth, it is expression ratio of CD3e+ to CD19+ cell, CD4+ to CD8+ cell, CD69+/CD3e+ cells, CD11a+/CD19+ cells and CD11b+/Gr-1+ cells and CD4+/CD25+ cells.Results : 1. In the MR-HA, the incidence of arthritis and the arthritis index were significantly decreased.2. In MR-HA, the levels of IL-6, IFN-γ, TNF-α, IL-1β, IgG, IgM and anti-collagen Ⅱ in serum of CIA mice and the level of IFN-γ, IL-4, IFN-γ/IL-4 ratio in CIA mouse spleen cell culture were significantly decreased.3. In histology, the cartilage destruction and synovial cell proliferation were decreased in the MR-HA, and the collagen fiber expressions in the MR-HA were similar with that of the Normal group.4. In the MR-HA, the expression ratio of CD3e+ to CD19+ cell and CD4+ to CD8+ cell were similarly maintained as Normal group in lymph nodes, and CD69+/CD3e+ cells and CD11a+/CD19+ cells were decreased in lymph nodes, and CD11b+/Gr-1+ cells and CD4+/CD25+ cells were decreased in synovium.Conclusion : These results suggest that MR-HA at St36 has an effect to control synovial cell proliferation and cartilage destruction in rheumatoid arthritis, as well as prophylaxis is important to treat rheumatoid arthritis in clinic.

海桐皮藥鍼이 Collagen-induced Arthritis 억제 및 면역조절에 미치는 영향

김영화,이현 대한침구의학회 2007 대한침구의학회지 Vol.24 No.5

Objectives : The purpose of this study was to analyze the effects of Erythrinae Cortex herbal- acupuncture solution(EC-HAS) at the Joksamni(ST36) of mice with collagen II-induced arthritis(CIA). Methods : The author performed several experimental procedures to observe the effects of the EC-HAS at the arthritis. The severity of arthritis, changes of cytokine level and antibody level, histological changes of the CIA mouse joint were analyzed. Results : 1. The incidence of arthritis and arthritis index were significantly decreased in the cases which were treated with the EC-HA. 2. Cartilage destruction and synovial cell proliferation were reduced, and the expression of the collagen fibers was similar with that of the normal group. 3. The levels of IL-6, IFN-γ, TNF-α, IL-1β in serum of the CIA mice which were treated with the EC-HA were significantly decreased compared with those of the normal group. 4. The levels of IgG, IgM and anti-collagen Ⅱ in serum of CIA mice when they treated with the EC-HA were significantly decreased compared with those of the normal group. 5. The expression ratio of CD4+ to CD8+ cells in the EC-HA treated mice were maintained as much as the normal group of the lymph nodes in the CIA mice. 6. The CD3e+CD69+ and CD11b+Gr-1+ cell populations in the knee joint were significantly decreased in the EC-HA treated group. Conclusions : These results suggest that the EC-HA at the ST36 may be responsible roles to control on the synovial cell proliferation and to prevent the cartilage destruction in rheumatoid arthritis. These results will be important supporting evidence for the practical use of the EC-HA at rheumatoid arthritis clinic in the future. Objectives : The purpose of this study was to analyze the effects of Erythrinae Cortex herbal- acupuncture solution(EC-HAS) at the Joksamni(ST36) of mice with collagen II-induced arthritis(CIA). Methods : The author performed several experimental procedures to observe the effects of the EC-HAS at the arthritis. The severity of arthritis, changes of cytokine level and antibody level, histological changes of the CIA mouse joint were analyzed. Results : 1. The incidence of arthritis and arthritis index were significantly decreased in the cases which were treated with the EC-HA. 2. Cartilage destruction and synovial cell proliferation were reduced, and the expression of the collagen fibers was similar with that of the normal group. 3. The levels of IL-6, IFN-γ, TNF-α, IL-1β in serum of the CIA mice which were treated with the EC-HA were significantly decreased compared with those of the normal group. 4. The levels of IgG, IgM and anti-collagen Ⅱ in serum of CIA mice when they treated with the EC-HA were significantly decreased compared with those of the normal group. 5. The expression ratio of CD4+ to CD8+ cells in the EC-HA treated mice were maintained as much as the normal group of the lymph nodes in the CIA mice. 6. The CD3e+CD69+ and CD11b+Gr-1+ cell populations in the knee joint were significantly decreased in the EC-HA treated group. Conclusions : These results suggest that the EC-HA at the ST36 may be responsible roles to control on the synovial cell proliferation and to prevent the cartilage destruction in rheumatoid arthritis. These results will be important supporting evidence for the practical use of the EC-HA at rheumatoid arthritis clinic in the future.

The Effect of Human Placental Extract on Rheumatoid Arthritis in an Animal Model

Jeong Dong Park,신희석,Sang-Il Lee,A Ram Kim,Jong Moon Park,Sang-Yeop Shin,Jun Hwa Shin,Seung Won Moon,Hyun Park,오민균 대한재활의학회 2012 Annals of Rehabilitation Medicine Vol.36 No.2

Objective To assess the effi cacy of human placental extract (HPE) in an animal model of rheumatoid arthritis (RA). Method We used (i) KRN C57BL/6 TCR transgenic x NOD mice (KBx/N) serum transfer arthritis and (ii) collageninduced arthritis (CIA) mice to evaluate the effi cacy of HPE (1 ul or 100 ul, intra-peritoneal, three times per week)on RA. Incidence, severity of arthritis, and hind-paw thickness were quantifi ed. Joint destruction was analyzed using modifi ed mammographic imaging. Histopathological analysis for infl ammation, cartilage, and osteoclasts was performed using Hematoxylin-eosin (H-E), safranin-O, and tartrate-resistant acidic phosphatase (TRAP). ELISAs were used for detection of various cytokines in serum and joint tissue. Results Th ere were no signifi cant diff erences in incidence of arthritis, clinical scores of arthritis, and hind-paw thickness between HPE-treated and vehicle-treated groups for up to 2 weeks in the KBx/N serum transfer arthritis model. Histopathological analysis also showed no diff erences 2 weeks after treatment. Levels of TNF-α, IL-1β, IL-6, IL-10, and RANKL in serum and joint tissues were similar in all groups. Furthermore, there were no diff erences in clinical, radiological, and histological parameters between HPE-treated and vehicle-treated group for 3 weeks in the CIA model. Conclusion Systemic treatment with HPE has no benefi cial eff ects on arthritis in animal models of RA. Th erefore,indiscreet use of HPE in RA should be forbidden.

류마티스 관절염 환자에서의 soluble transferrin receptor측정의 유용성

전래희,김신규,이혜림,이웅수 대한임상병리학회 1998 대한임상병리학회지 Vol.18 No.3

류마티스 관절염 환자에서의 soluble transferrin receptor측정의 유용성

전래희,김신규,이혜림,이웅수 대한임상병리학회 1998 대한임상병리학회지 Vol.21 No.3

류머티스 관절염과 골관절염 환자에서 Transforming growth factor β의 발현 양상

김채기,윤원찬,송용호,김상경,최정윤,Kim, Chae-Gi,Yoon, Wern Chan,Song, Yong-Ho,Kim, Sang-Gyung,Choe, Jung-Yoon 대한면역학회 2001 Immune Network Vol.1 No.3

The transforming growth $factor-{\beta}$ ($TGF-{\beta}$) is a multifunctional cytokine modulating the onset and course of autoimmune disease as shown in experimental models. In synovial inflammation, there is a potential role for $TGF-{\beta}$ in repairment, the inhibition of cartilage and bone destruction, and the down-regulation of immune response. The biologic effects of $TGF-{\beta}$ depend on the cell type, the isoform and the availability of active $TGF-{\beta}$. We investigated $TGF-{\beta}$ expression in patients with rheumatoid arthritis (RA) and compared to those of osteoarthritis (OA). And we determined a correlation between $TGF-{\beta}1$ and $TGF-{\beta}2$, and also the relationships between each $TGF-{\beta}$ isoform and the parameters for disease activity of RA. Methods: The study population consisted of 20 patients with RA and 20 patients with OA. The commercial ELISA kit was used to study $TGF-{\beta}1$ and $TGF-{\beta}2$ levels in peripheral blood (PB) and synovial fluids (SF). Results: 1) While PB $TGF-{\beta}1$ level was of no difference between RA and OA patient groups, SF $TGF-{\beta}1$ level was higher in RA group than OA group. Similarly, PB $TGF-{\beta}2$ levels of RA and OA groups was not different, but SF $TGF-{\beta}2$ levels was higher in RA group than OA group. 2) In patients with RA, the $TGF-{\beta}1$ levels were higher than $TGF-{\beta}2$ in both the PB and SF, while in patients with OA, there showed higher readings for $TGF-{\beta}1$ than $TGF-{\beta}2$ in SF but no difference between $TGF-{\beta}1$ and $TGF-{\beta}2$ levels in PB. 3) In patients with RA, there were no correlations between PB $TGF-{\beta}1$ and PB $TGF-{\beta}2$ levels, nor between SF $TGF-{\beta}1$ and SF $TGF-{\beta}2$ levels. At the same way, there was no correlation between PB $TGF-{\beta}1$ and SF $TGF-{\beta}1$ levels, nor between each levels of $TGF-{\beta}2$ in patients with RA. 4) There was also no correlation between each $TGF-{\beta}$ isoform and the parameters for disease activity such as ESR, CRP, tender joint count, swollen joint count, rheumatoid factor, and the duration of morning stiffness except between in PB $TGF-{\beta}1$ and disease duration of RA (r=0.637, p<0.01). Conclusion: Each $TGF-{\beta}$ isoforms were higher in synovial fluid of patients with RA than that of patients with OA. The data from the RA patients demonstrated different patterns of expressions of the isoforms depending on which compartment (PB or SF) was investigated. The quantification of different $TGF-{\beta}$ isoform is thought to be important when $TGF-{\beta}$ is measured under disease conditions of RA.

류마티스 관절염환자와 골관절염환자의 요중 Hydroxypyridinium Crosslinks 의 측정과 임상적 유용성에 관하 연구

정성광(Sung Kwang Jung),이윤우(Yun Woo Lee),신보문(Bo Moon Shin),김종원(Jong Won Kim) 대한내과학회 1997 대한내과학회지 Vol.53 No.2

N/A Objectives: To evaluate the urinary concentrations of hydroxyridinium crosslinks of collagen in patients with osteoarthritis(OA) or rheumatoid arthritis(RA), and to compare its clinical correlation with the classic indices of the disease activity of RA. Methods: Concentrations of urinary pyridinoline (Pyd) and deoxypyridinoline(Dpd) were measured in urinary samples collected from 18 control patients, 35 patients with OA, 45 patients with RA by competitive enzyme immunoassay using microplate coated with monoclonal antibody. Results: 1) Mean urinary concentrations of Pyd in OA patients were 33.5nmol/mmol creatinine, in RA patients were 50.0nmol/mmol creatinine which were higher than the values in controls (25.1 nmol/mmol creatinine). Also, mean concentrations of Dpd in OA patients were 9.2nmol/mmol creatinine, in RA patients were 10.1nmol/mmol creatinine which were higher than the values in controls(5.6nmol/mmol creatinine)(p<0.01). 2) Mean urinary concentration of Pyd was 50.0 nmol/mmol creatinine in RA patients, which was significantly higher than the values in OA(33.5 nnmol/mmol creatinine)(p<0.05), but the mean Dpd concentratians were not significantly different between the two groups. 3) The concentrations of urinary Pyd in RA patients was significantly correlated with the biologic markers indicating inflammatory activity such as ESR(r=0.68, p<0.001), CRP(r=0.72, p<0.001) and the number of tender joint(r=0.66, p<0.01) Conclusion : Urinary concentrations of Pyd and Dpd were significantly higher in OA and RA patients than in controls, Especially urinary Pyd concentrations were significantly increased in RA patients than in OA patients, and strongly correlated with disease activity index of rheumatoid arthritis. The mean Dpd concentration, bone specific analogue, in RA patients was not significantly different from that of OA patients and it was not correlated with disease activity index Thus measurement of urinary Pyd might provide a sensitive, noninvasive biochemical marker for studying activity of RA.

Evidence from a Multidimensional Health Assessment Questionnaire (MDHAQ) of the Value of a Biopsychosocial Model to Complement a Traditional Biomedical Model in Care of Patients with Rheumatoid Arthritis

( Theodore Pincus ),( Jacquelin R Chua ),( Kathryn A Gibson ) 대한류마티스학회 2016 대한류마티스학회지 Vol.23 No.4

Patient self-report questionnaires such as a multidimensional health assessment questionnaire (MDHAQ) have advanced knowledge concerning prognosis, care, course and outcomes of rheumatoid arthritis (RA). The MDHAQ may overcome some limitations of a “biomedical model,” the dominant paradigm of contemporary medical services, including limitations of laboratory tests, radiographs, joint counts, and clinical trials, to predict and depict the long-term course and outcomes of RA. A complementary “biopsychosocial model” captures components of a patient medical history on patient questionnaires as quantitative, standard, “scientific” scores for physical function, pain, fatigue, and other problems, rather than as “subjective” narrative descriptions. A rationale for a biopsychosocial model in RA includes the importance of a patient history in diagnosis and management compared to biomarkers in many chronic diseases such as hypertension and diabetes. Some important observations which support a biopsychosocial model in RA based on patient questionnaires include that MDHAQ physical function scores are far more significant than radiographs or laboratory tests to predict severe RA outcomes such as work disability and premature death; patient self-report measures are more efficient than tender joint counts and laboratory tests to distinguish active from control treatments in RA clinical trials involving biological agents; and MDHAQ scores are more likely than laboratory tests to be abnormal at presentation and to document incomplete responses to methotrexate at initiation of biological agents. Patient questionnaires can save time for doctors and patients, and improve doctor-patient communication. A standardized database of MDHAQ scores consecutive patients over long periods might be considered by all rheumatologists in routine clinical care. (J Rheum Dis 2016;23:212-233)

足三里 秦?藥鍼이 생쥐의 Collagen-induced Arthritis 에 미치는 影響

박정현,이현,임윤경 경락경혈학회 2007 Korean Journal of Acupuncture Vol.24 No.3

Objectives & Methods : The purpose of this study is to observe the effects of Gentianae macrophyllase Radix herbal-acupuncture solution(GR-HAS) at Joksamni(ST36) on Collagen-induced arthritis(CIA) in DBA/1J mice. The author performed several experimental items to analyze arthritis evaluation, change of weight, spleen size and adhesion rate, change of cytokine level, IgG, IgM and anti-collagen Ⅱ, change of immunocyte count, histological change of CIA mouse joint related with RA.