표제지
감사의 글
목차
초록 6
머리말 9
방법 13
1. 맥락막신생혈관 모델 13
2. 약물 주입 14
3. 형광안저혈관 조영 15
4. 조직학적 분석 16
5. 면역조직화학 염색 17
6. RT-PCR과 real-time quantitative RT-PCR 18
7. 통계적 분석 20
결과 21
1. 실험동물의 무게 및 활동성 21
2. 소라페닙의 맥락막신생혈관 형광 누출 억제 효과 22
3. 소라페닙의 맥락막신생혈관 생성 억제 효과 25
4. 소라페닙의 혈관내피성장인자 및 혈소판 유래성장인자 발현 억제 효과 28
고찰 30
참고문헌 39
ABSTRACT 54
Table 1. List of Primers used in this study and their sequences 20
Table 2. Comparison of body weights between control rats and sorafenib-treated rats 21
Table 3. Comparison of activities between control rats and sorafenib-treated rats 22
Fig. 1. Fundus photographs and fluorescein angiograms of the retinal lesions of sorafenib-treated groups and control group 14 day after laser-induced CNV in rat retina. (A, B) control group (C,D) sorafenib 10mg/kg-treated group (E,F) sorafenib 30 mg/kg-treated group. Signal intensities were presented from 0(darkest) to 1... 23
Fig. 2. Effect of sorafenib on CNV fluorescein leakage 14 days after laser-induced CNV in rat retina. The average fluorescein intensity score of the eyes treated with vehicle only, sorafenib 10, 30mg/kg were 0.925±0.074 and 0.763±0.176, 0.658±0.147 respectively. The error bars indicate standard error of the mean. *, P<0.05 compared to control. 24
Fig. 3. Effect of sorafenib on CNV thickness 14 days after laser-induced CNV in rat retina. Light micrographs of Hematoxylin and Eosin stained sections of the CNV lesions in vehicle-treated rat 26
Fig. 4. Effect of sorafenib on CNV thickness 14 days after laser-induced CNV in rat retina. The average CNV thickness of the eyes treated with vehicle only, sorafenib 10, 30mg/kg were 81.731±11.597 μm. 60.036±21.052 μm. and 38.314±17.203 μm respectively. The bars indicate standard error of the mean. *P<0.05 compared to control. 26
Fig. 5. The volume of CNV 14 days after laser-induced CNV in rat retina. Light micrographs of Hematoxylin and Eosin (Left column) and Masson trichrome (Right) stained sections of the CNV lesions in vehicle-treated rat. 27
Fig. 6. Photomicrographs of immunofluorescence staining for VEGF 28
Fig. 7. Effect of sorafenib on expression of VEGF, PDGF, ICAM-1, and MCP-1 mRNA 3 days after laser-induced CNV. Real-time quantitaitve RT-PCR analysis revealed that VEGF, PDGF, ICAM-1, and MCP-1 mRNA expression in sorafenib-treated rats were lower than those in vehicle-treated(control) rats. But only VEGF and ICAM-1 mRNA levels in sorafenib(30mg/kg)-treated rats were significantly dereased than those in vehicle treated rats. * P<0.05 compared with control group. 29