표제지
목차
국문 초록 13
Ⅰ. 서론 15
Ⅱ. 재료 및 방법 20
A. 시험동물 20
B. 전립선 비대증 모델 및 치료모델 제작 21
C. 체중 및 장기무게 측정 23
D. 혈청 분리 및 혈액 생화학 분석 24
E. 조직 병리 관찰 25
F. 전립선 조직에서 DNA fragmentation 변화 관찰 26
G. 혈청 및 조직 내 전립선 비대증 바이오마커 변화 확인 27
H. Transcriptome 분석 28
I. 장내 마이크로바이옴 분석 30
J. 통계 분석 32
Ⅲ. 결과 33
A. 전립선 비대증 유도와 finasteride 처치로 인한 체중 및 장기 무게와 간 및 신장 기능의 변화 33
B. 전립선 비대증 유도와 finasteride 처치로 인한 전립선 변화 35
C. 전립선 비대증 유도와 finasteride 처치로 인한 호르몬 마커 및 PSA 수치 변화 37
D. 전립선 비대증 유도와 finasteride 처치로 인한 전립선 apoptosis 변화 39
E. 전립선 비대증 유도와 finasteride 처치로 인한 염증 마커 변화 41
F. 전립선 비대증 유도와 finasteride 처치가 장내 마이크로바이옴 다양성 및 구성에 미치는 영향 43
G. 전립선 비대증 유도와 finasteride 처치로 인한 주요 장내 마이크로바이옴의 변화 48
H. 전립선 비대증 유도로 인한 장내 마이크로바이옴의 변화 53
I. Finasteride 처치로 인한 장내 마이크로바이옴의 변화 57
J. 전립선 비대증 유도로 인해 변화한 바이오마커 사이의 상관관계 61
K. 전립선 비대증 유도로 인해 변화한 장내 마이로바이옴과 바이오마커 사이의 상관관계 63
L. 전립선 비대증 모델과 치료모델에서의 Lactobacillus spp. 변화 68
Ⅳ. 고찰 70
Ⅴ. 참고 문헌 77
ABSTRACT 83
Table 1. Primer sequence for real-time PCR analysis (5'-3') 29
Figure 1. Effect of BPH induction or finasteride treatment on Body and Organ weight and the function of liver and kidney. The change of Body... 34
Figure 2. The change of prostate profiles after BPH induction and finasteride treatment. Prostate weight (A), prostate volume (B) and prostate... 36
Figure 3. The change of BPH biomarkers after BPH induction and finasteride treatment. The levels of 5α-reductase (A) and DHT (B) in serum,... 38
Figure 4. The change of apoptosis in prostate tissue after BPH induction and finasteride treatment. DNA fragmentation in prostate were measured by... 40
Figure 5. The change of transcriptome in prostate tissue after BPH induction and finasteride treatment. The transcriptomes of inflammatory... 42
Figure 6. Microbial diversity in bacterial community after BPH induction and finasteride treatment. Observed OTUs (A) and Shannon index (B) in... 45
Figure 7. Bacterial composition after BPH induction and finasteride treatment. Top microbes at the phylum (A, B), the family (C, D) and the... 46
Figure 8. Hierarchical clustering of most abundant bacteria. Bacterial family (A) and genera (B) are labeled in the heat map using Spearman's... 47
Figure 9. Alteration of relative bacterial abundance after BPH induction and finasteride treatment. Significant differences were identified by LEfSe... 49
Figure 10. The abundant microbes in control group. Abundant microbes at the family and genus levels in control group selected based on LEfSe... 50
Figure 11. The abundant microbes by BPH induction. Abundant microbes at the family and genus levels in BPH group selected based on LEfSe... 51
Figure 12. The abundant microbes by finasteride treatment. Abundant microbes at the family and genus levels selected in BPH+Fina group based... 52
Figure 13. Alteration of relative bacterial abundance by BPH induction. Significant differences were identified by LEfSe analyses as p〈0.05, using... 54
Figure 14. Decreased bacterial genera by BPH induction. Decreased microbes selected based on LEfSe analyses in BPH group (A, B). Statistical... 55
Figure 15. Increased bacterial genera by BPH induction. Increased microbes selected based on LEfSe analyses in BPH group (A-G). Statistical... 56
Figure 16. Alteration of relative bacterial abundance by finasteride treatment. Significant differences were identified by LEfSe analyses as... 58
Figure 17. Decreased bacterial genera by finasteride treatment. Decreased microbes selected based on LEfSe analyses in BPH+Fina group (A-C).... 59
Figure 18. Increased bacterial genera by finasteride treatment. Increased microbes selected based on LEfSe analyses in BPH+Fina group (A-G).... 60
Figure 19. The correlation between BPH biomarkers. The correlation were conducted between prostate profiles (A-C) and hormonal markers (D-E) with... 62
Figure 20. The correlation between bacterial genera and hormonal markers. Spearman's rank correlation was used to analyze the correlation... 65
Figure 21. The correlation between bacterial genera and apoptosis markers. Spearman's rank correlation was used to analyze the correlation... 67
Figure 22. Alteration of relative bacterial abundance in spices level after BPH induction and finasteride treatment. Significant differences were... 69
Scheme 1. The procedure of BPH induction and finasteride treatment, and gut microbiome analysis 22