Coniferyl aldehyde protects against radiation enteropathy by enhancing endothelial cell survival
- 주제(키워드) Coniferyl aldehyde , Radiation enteropathy , Endothelial cell , small intestine
- 발행기관 고려대학교 대학원
- 지도교수 고영규
- 지도교수 이해준
- 발행년도 2015
- 학위수여년월 2015. 2
- 학위구분 석사
- 학과 일반대학원 생명과학과
- 세부전공 세포생물학
- 원문페이지 57 p
- 실제URI http://www.dcollection.net/handler/korea/000000058284
- 본문언어 영어
- 제출원본 000045827698
초록/요약
Radiation enteropathy is a common complication in cancer patients. The aim of this study was to investigate whether radiation-induced intestinal injury could be alleviated by coniferyl aldehyde (CA), an HSF1-inducing agent that increases cellular HSP70. We administered CA systemically to mice with radiation enteropathy following abdominal irradiation, a model mimicking the clinical situation of cancer patients. The data showed that CA clearly alleviated radiation-induced intestinal damage early, as reflected by survival and histopathology data, as well as attenuated delayed enteritis. Furthermore, CA prevented microvascular death in the lamina propria during the acute phase and preserved the endothelial cell population during the delayed phase. In vitro, CA protected against not only radiation-induced apoptosis of both endothelial and epithelial cells, but also angiogenesis in endothelial cells during irradiation, indicating that its beneficial effects are largely due to its protection of endothelial cells in the intestine. Our results provide novel insight into the effects of CA and suggest its role as a therapeutic candidate for radiation-induced enteropathy, offering protection against angiogenic activity and helping rescue the intestinal microenvironment for re-proliferation of the intestinal epithelium.
more목차
List of Contents..........................................................................i
List of Figures .........................................................................iii
Abstract ...................................................................................iv
Introduction
1. Radiation Enteropathy...........................................................1
2. Endothelial Injury..................................................................2
3. Coniferyl Aldehyde.................................................................3
Materials and Methods
1. Reagent....................................................................................4
2. Animals....................................................................................4
3. Irradiation...............................................................................4
4. Tissue Collection.....................................................................5
5. Immunohistochemistry .........................................................5
6. TUNEL (Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling) assay.......................................................6
7. Masson’s Trichrome staining.................................................6
8. Hematoxylin and Eosin Staining...........................................7
9. Cells..........................................................................................7
10. Western Blotting.....................................................................7
11. Fluorescence-activated Cell Sorting.....................................8
12. MTT assay..............................................................................9
13. Tumor Bearing Mice...............................................................9
14. Statistics...................................................................................9
Results
1. CA prolonged survival against total body irradiation......10
2. Abdominal irradiation model..............................................13
3. CA inhibits apoptotic epithelial and endothelial cell death after irradiation....................................................................16
4. CA protects against acute radiation-induced intestinal injury......................................................................................19
5. CA attenuates delayed radiation enteropathy....................23
6. CA is more protective of endothelial cells than epithelial cells.........................................................................................29
7. CA did not contribute to cancer cell protection against radiation................................................................................35
Discussion ..............................................................................................39
References .............................................................................................44
Abstract in Korean ............................................................................49
Acknowledgements ............................................................................50
