표제지
목차
국문초록 12
제1장 서론 15
제1절 연구의 배경 및 필요성 15
제2절 연구의 목적 21
제3절 연구의 구성 및 절차 22
1. 연구의 구성 22
2. 연구의 절차 24
3. 연구의 모형 25
제4절 용어의 정의 26
1) 대식세포 26
2) Cytokine 26
3) 전염증성 cytokine 27
4) TNF-α 27
5) 염증성 효소 27
6) 일산화질소 27
7) 프로스타글란딘 28
8) 연골 28
9) 관절 28
10) 관절염 29
11) 골관절염 29
제2장 이론적 배경 30
제1절 항관절염 30
1. 항관절염 30
2. 항관절염의 치료제 31
3. 항관절염의 선행연구 35
제2절 백출(白朮)과 구기자(枸杞子) 38
1. 백출과 구기자 38
2. 백출(白朮)과 구기자(枸杞子)의 선행연구 44
제3절 항관절염 치료제의 산업화 현황 51
제4절 백출(白朮)과 구기자(枸杞子)의 산업화 현황 52
제3장 연구 재료 및 방법 56
제1절 연구 재료 및 시약 56
1. 백출 및 구기자 56
2. 실험동물 56
3. 시약 57
제2절 실험방법 57
1. 추출 및 시료 제조 57
2. 세포배양 59
3. 세포독성 59
4. Cytokine 측정 60
5. NO 측정 62
6. PGE2 측정 63
7. Western blotting 분석 63
8. 실험동물군 설정 64
9. 골관절염 유도 65
10. 관절염 지수 평가 67
11. 체중 측정 및 무릎 두께와 온도 측정 68
12. 연골 손상 육안평가 68
13. 혈청 분리 68
14. 혈청 CRP 측정 69
15. 혈청 cytokine 및 PGE2 측정 69
16. 조직병리학적 관찰 69
제3절 통계처리 및 분석 73
제4장 연구의 결과 74
1. EAL의 세포독성 74
2. RAW264.7 대식세포에서 염증성 cytokine 분비 76
3. RAW264.7 대식세포에서 NO 및 PGE2 분비 80
4. 골관절염 실험동물에서 관절염 개선 효과 84
5. 골관절염 실험동물에서 혈액 내 CRP 변화 92
6. 골관절염 실험동물에서 혈액 내 전염증성 cytokine 변화 94
7. 골관절염 실험동물에서 혈액 내 NO 및 PGE2 변화 98
제5장 결론 및 제언 101
제1절 고찰 101
제2절 결론 105
제3절 연구의 의의 및 시사점 107
참고문헌 110
ABSTRACT 125
Table 1. Causes, symptoms, and treatment of knee cartilage damage by age 33
Table 2. The origin of the Araliae Continentalis Radix in KP, CP and JP 39
Table 3. Major constituents of Atractylodis Rhiaoma Alba 40
Table 4. The origin of the Lycii Fructus in KP, CP and JP 41
Table 5. Major constituents of Lycii Fructus 43
Table 6. Previous studies on Lycii Fructus 50
Table 7. The Industrialiaztion of Anti-Arthritis Drugs 51
Table 8. The Industrialiaztion of Atractylodis rhizoma alba 53
Table 9. The Industrialiaztion of Lycii fructus 54
Table 10. Clinical evaluation of arthritis score 67
Fig. 1. Research protocol. 24
Fig. 2. Research model. 25
Fig. 3. Schematic diagram illustrating the extraction procedure for the mixture of Atractylodis rhizoma alba and Lycii fructus. 58
Fig. 4. The reduction of MTT by a reductase in a living cell. 61
Fig. 5. A method for detection of cytokine or PGE2 using a commercially available ELISA kit. 61
Fig. 6. A Griess method for determining nitrite concentration contained in culture media. 62
Fig. 7. A procedure for Western blotting analysis. 65
Fig. 8. Structural changes in the development of osteoarthritis with showing the normal joint (a) and the diseased joint (b). 66
Fig. 9. Experimental design and assessment of a model of MIA-induced osteoarthritis. 67
Fig. 10. Chemical structures of hematoxylin and eosin dyes and their binding targets in animal tissue. 71
Fig. 11. Staining procedure of animal tissue using H&E dyes. 72
Fig. 12. Effects of EAL on the viability of RAW264.7 macrophages. RAW264.7 macrophages were incubated for 24 h with vehicle... 75
Fig. 13. Effects of EAL on LPS-induced TNF-α production in RAW264.7 macrophages. RAW264.7 macrophages were... 77
Fig. 14. Effects of EAL on LPS-induced IL-1β production in RAW264.7 macrophages. RAW264.7 macrophages were... 78
Fig. 15. Effects of EAL on LPS-induced IL-6 production in RAW264.7 macrophages. RAW264.7 macrophages were... 79
Fig. 16. Effects of EAL on iNOS and COX-2 expression in RAW264.7 macrophages. RAW264.7 macrophages were incubated for 1 h... 81
Fig. 17. Effects of EAL on LPS-induced NO (nitrite) production in RAW264.7 macrophages. RAW264.7 macrophages were... 82
Fig. 18. Effects of EAL on LPS-induced PGE2 production in RAW264.7 macrophages. RAW264.7 macrophages were... 83
Fig. 19. Representative pictures showing the clinical observations on the left knees of SD rats (red arrows). Normal rats were... 85
Fig. 20. Effect of EAL on swelling of left knee in MIA-treated SD rats. Normal rats were neither injected with MIA nor treated... 86
Fig. 21. Representative pictures showing the knee skin temperature of SD rats. Normal rats were neither injected with MIA nor... 87
Fig. 22. Effect of EAL on skin temperature of left knee in MIA-treated SD rats. Normal rats were neither injected with... 88
Fig. 23. Representative pictures showing the left knee joints of SD rats. Normal rats were neither injected with MIA nor treated... 89
Fig. 24. Histopathological observation of the sections of the left knee joints of SD rats. Normal rats were neither injected with... 90
Fig. 25. Effect of EAL on arthritis progression in MIA-treated SD rats. Normal rats were neither injected with MIA nor treated... 91
Fig. 26. Effect of EAL on serum CRP in MIA-treated SD rats. Normal rats were neither injected with MIA nor treated with... 93
Fig. 27. Effect of EAL on serum TNF-α in MIA-treated SD rats. Normal rats were neither injected with MIA nor treated with... 95
Fig. 28. Effect of EAL on serum IL-1β in MIA-treated SD rats. Normal rats were neither injected with MIA nor treated with... 96
Fig. 29. Effect of EAL on serum IL-6 in MIA-treated SD rats. Normal rats were neither injected with MIA nor treated with... 97
Fig. 30. Effect of EAL on serum NO (nitrite) in MIA-treated SD rats. Normal rats were neither injected with MIA nor treated... 99
Fig. 31. Effect of EAL on serum PGE2 in MIA-treated SD rats. Normal rats were neither injected with MIA nor treated with... 100