초록 ▼

인간의 경피증 연구에 다양한 동물모델이용되고 있는데, 블레오마이신을 매일 3-4주간 피하주사하는 모델이 많이 이용되고 있다. 그러나 매일 블레오마이신을 주사하여야 하므로 시간 및 노력의 낭비가 심하다.
1차년도에서는 새로 개발된 methylcellulose gel을 drug delivery system으로 이용하여 블레오마이신을 1주일에 한번씩만 주사하여도 경피증 모델이 만들어지는 편리한 동물모델을 개발하였다. 2차년도에는 이 편리한 동물모델을 이용하여 실험실실험에서 경피증 치료에 도움이 될 것으로 알려진 경구용 플라보노이드인

인간의 경피증 연구에 다양한 동물모델이용되고 있는데, 블레오마이신을 매일 3-4주간 피하주사하는 모델이 많이 이용되고 있다. 그러나 매일 블레오마이신을 주사하여야 하므로 시간 및 노력의 낭비가 심하다.
1차년도에서는 새로 개발된 methylcellulose gel을 drug delivery system으로 이용하여 블레오마이신을 1주일에 한번씩만 주사하여도 경피증 모델이 만들어지는 편리한 동물모델을 개발하였다. 2차년도에는 이 편리한 동물모델을 이용하여 실험실실험에서 경피증 치료에 도움이 될 것으로 알려진 경구용 플라보노이드인 아피제닌의 예방 및 치료효과를 보고자 하였으나 결론적으로 효과가 없음을 증명하였다.

Abstract ▼

Systemic sclerosis is a multisystem connective tissue disease of unknown etiology. This disease is characterized by the functional and structural abnormalities of microvasculature, the fibrosis of skin and various internal organs, immune dysregulation, and autoimmunity. There are several animal mode

Systemic sclerosis is a multisystem connective tissue disease of unknown etiology. This disease is characterized by the functional and structural abnormalities of microvasculature, the fibrosis of skin and various internal organs, immune dysregulation, and autoimmunity. There are several animal models for research on the pathogenesis of systemic sclerosis and on potential therapeutic agents.
In particular a bleomycin (BLM)-induced SSc model involving daily subcutaneous injection of BLM into the back skin of susceptible strains of mice has been developed and is widely used. However, daily injection is time-consuming and inconvenient. The objective of the 1st year study was to develop the convenient animal model of scleroderma, which is induced by weekly injection of BLM with methylcellulose(MC ) gelas adrug delivery system. We have recent lydeveloped thermo-reversible combination gels that can be injected subcutaneously and into joint cavities, and are generated in aqueous solution by forming a complex coacervate with a substance of interest and cationic macromolecules, followed by co-formulation with MC as a negative thermosensitive polysaccharide. In vitro release test of bleomycin, BLM was released relatively slowly with an initial burst. By 4 days, more than 80% of the BLM had been released from the MC gel. Dermal thickness was significantly increased in the MC-BLM injection group compared to the MC-PBS injection group. The MC-BLM injection group had a greater fibrosis score than the MC-PBS group. The number of a-SMA-positive cells was larger in the MC-BLM group than the MC-PBS group but with marginal significance. Taken together, our observations demonstrate that weekly injections of BLM incorporated in an MC gel can induce dermal fibrosis in susceptible mice, and that this conveniently modified model of SSc may facilitate research on the pathogenesis and treatment of systemic sclerosis.
The objective of the 2nd year study was to investigate the therapeutic role of the physiologic concentration of dietary flavonoid apigenin in modified BLM-induced systemic sclerosis animal model. Non-toxic and non-mutagenic apigenin plays role in many cellular processes. Apigenin inhibited cell proliferation of myofibroblast and gene expression of alpha 1(1) collagen and smooth muscle actin. The physiologic concentration of apigenin inhibited endothelin-1-induced contraction of collgen gel, in vitro model of extracellular matrix remodeling. BLM-induced animal model of scleroderma was successfully developed in terms of dermal thickness, semi-quantitative analysis of fibrosis, and collagen content of lung tissue. However, intraperitoneal injection of apigenin (1.0mg/kg/day or 2.5mg/kg/day) did not show any therapeutic efficacy on scleroderma phenotypes. Conclusively, although in vitro data suggested that dietary concentration of apigenin might modulate myofibroast activity in vivo, we failed to show the therapeutic efficacy in animal model of scleroderma.

목차 Contents

• 표 지 ... 1
• 제출문 ... 3
• 보고서 요약서 ... 4
• 요 약 문 ... 5
• SUMMARY ... 6
• 6. 연구 성과 실적 및 향후 계획 ... 7
• 6.1 총괄연구개발과제의 연구성과 실적 및 향후 계획 ... 7
• 6.2 연구성과 유형별 세부 내역 ... 8
• 7. 참여연구원 현황표 ... 11
• II. 총괄연구과제 연구결과 ... 12
• 1. 연구개발과제의 배경 및 필요성 ... 13
• 2. 국내외 기술개발 현황 ... 18
• 3. 연구개발과제의 추진체계 ... 18
• 4. 연구개발수행 내용 및 결과 ... 19
• 5. 목표달성도 및 관련분야 기여도 ... 32
• 6. 향후 연구성과 추진 계획 ... 33
• 7. 연구개발결과의 파급효과 ... 33
• 8. 연구개발결과의 활용계획 ... 34
• 9. 연구개발과정에서 수집한 해외과학기술정보 ... 34
• 10. 참고문헌 ... 34
• IV. 첨부서류 ... 36
• 끝페이지 ... 37