표제지
목차
국문 요약문 13
Ⅰ. 서론 15
Ⅱ. 문헌 고찰 19
1. 폐암 발생 현황과 암 악액질 19
1) 폐암 발생 현황 19
2) 암 악액질(cancer cachexia) 21
2. 시스플라틴과 근위축 22
1) 시스플라틴의 구성 및 작용기전 22
2) 시스플라틴 치료의 부작용 27
3) 시스플라틴에 의한 근위축 기전 27
3. 나리루틴의 구성 및 생리활성 35
Ⅲ. 연구 내용 및 방법 39
1. 동물실험 연구 디자인 39
2. Grip strength and hanging wire test 42
3. Hematoxylin & eosin staining 42
4. Real-time quantitative polymerase chain reaction 42
5. Western blot analysis 43
6. 통계 분석 44
Ⅳ. 결과 46
1. 체중 변화 46
2. 종양 조직 크기 49
3. 식이 섭취량 52
4. 나리루틴의 근력 증진 효과 55
1) Grip strength change 55
2) Hanging wire test 58
5. 나리루틴이 근육 무게 및 근섬유 감소에 미치는 영향 61
1) 근육 조직 무게 61
2) 근육 조직 병리학적 분석 64
6. 나리루틴의 단백질 분해 기전 억제 효과 68
1) 단백질 분해 기전 관련 지표 IL-6, JAK2, STAT3의 mRNA 발현 68
2) 단백질 분해 기전 관련 지표 TNFα, NF-κB 및 p38MAPK의 mRNA 및 단백질 발현 71
3) 단백질 분해 기전 관련 지표 MuRF1, MAFbx의 단백질 발현 74
7. 나리루틴의 단백질 분화 기전 촉진 효과 77
1) 단백질 합성 관련 지표 IGF-1R, PI3K, Akt, mTOR의 mRNA 및 단백질 발현 77
2) 근육분화 관련 지표 MyHC의 mRNA 발현 80
3) 근육분화 관련 지표 MyHC isoforms의 단백질 발현 83
8. 나리루틴의 미토콘드리아 생합성 증진 효과 86
9. 나리루틴이 미토콘드리아 다이나믹스에 미치는 영향 89
Ⅴ. 고찰 92
Ⅵ. 요약 및 결론 100
Ⅶ. 참고문헌 103
ABSTRACT 114
Table 1. Primer sequences used for the qRT-PCR analysis 45
Table 2. Final body weight and carcass weight 47
Table 3. Final tumor volume 50
Table 4. The effect of narirutin on food intake 53
Table 5. The effect of narirutin on grip strength 56
Table 6. The effect of narirutin on four-limb hanging 59
Table 7. The effects of narirutin on skeletal muscle tissues weight 62
Table 8. The effect of narirutin on the CSA of quadriceps muscle fiber 66
Table 9. The effects of narirutin on IL-6/JAK2/STAT3 pathway 69
Table 10. The effects of narirutin on TNFα/NF-κB and p38MAPK pathway 72
Table 11. The effects of narirutin on the expression of MuRF1 and MAFbx 75
Table 12. The effects of narirutin on IGF-1R/PI3K/Akt/mTOR pathway 78
Table 13. The effects of narirutin on the expression of myogenesis genes 81
Table 14. The effects of narirutin on the expression of myosin heavy chain isoforms 84
Table 15. The effects of narirutin on mitochondrial biogenesis 87
Table 16. The effects of narirutin on mitochondrial dynamics 90
Figure 1. Distribution of Cases and Deaths for the Top 10 Most Common Cancers in 2020 20
Figure 2. Cisplatin activation and DNA damage induction 24
Figure 3. Mechanism of action of cisplatin 26
Figure 4. Overview of the potential mechanisms leading to skeletal muscle wasting and weakness 30
Figure 5. Mitochondrial life cycle 34
Figure 6. The chemical structure of narirutin 36
Figure 7. Experimental design of study 41
Figure 8. Body weight changes during the experimental period 48
Figure 9. Tumor volumes during the experimental period 51
Figure 10. The effect of narirutin on food intake 54
Figure 11. The effect of narirutin on grip strength 57
Figure 12. The effect of narirutin on four-limb hanging 60
Figure 13. The effects of narirutin on skeletal muscle tissues weight 63
Figure 14. Representative H&E staining of the quadriceps muscle 65
Figure 15. The effect of narirutin on the CSA of quadriceps muscle fiber 67
Figure 16. The effects of narirutin on IL-6/JAK2/STAT3 pathway 70
Figure 17. The effects of narirutin on TNFα/NF-κB and p38MAPK pathway during muscle atrophy 73
Figure 18. The effects of narirutin on the expression of MuRF1 and MAFbx 76
Figure 19. The effects of narirutin on IGF-1R/PI3K/Akt/mTOR pathway 79
Figure 20. The effects of narirutin on the expression of myogenesis genes 82
Figure 21. The effects of narirutin on the expression of myosin heavy chain isoforms 85
Figure 22. The effects of narirutin on mitochondrial biogenesis 88
Figure 23. The effects of narirutin on mitochondrial dynamics 91
Figure 24. The effects of narirutin on cisplatin-induced muscle atrophy 102