The effect of necrosis inhibitor on dextran sulfate sodium induced chronic colitis model in mice
- 주제(키워드) Necrosis inhibitor , Chronic colitis
- 발행기관 고려대학교 대학원
- 지도교수 정성우
- 발행년도 2020
- 학위수여년월 2020. 8
- 학위구분 박사
- 학과 대학원 의학과
- 세부전공 내과학 전공
- 원문페이지 38 p
- UCI I804:11009-000000232374
- DOI 10.23186/korea.000000232374.11009.0001176
- 본문언어 영어
- 제출원본 000046046224
초록/요약
Background: Uncontrolled chronic inflammation is characteristic of inflammatory bowel disease (IBD). Necrosis is thought to be related with IBD. There are few studies about necrosis inhibition in IBD. The aim of this study is to investigate the effect of necrosis inhibitor (NI, NecroX-7) in dextran sulfate sodium (DSS) induced chronic colitis model of mice. Method: DSS induced chronic colitis mice model was used. Necrosis inhibitor (NI, NecroX-7) was administered intraperitoneal (3mg/kg, 30mg/kg) for every other day in first 5 days of three-week cycle. Three cycle of administration was done. The severity of colitis was evaluated by disease activity index (DAI), colon length, and histologic score. Pro-inflammatory cytokine mRNA expression was measured by real time PCR, Western blot assay and immunohistochemical staining. Result: Body weight change is reduced in DSS+NI3 group compared to DSS group. DAI was significantly low and in both NI treated groups (DSS+NI3 and DSS+NI30 group) than DSS group. The length of colon was longer and histologic score is lower in NI treated group. NI treated groups showed the reduced expression of pro-inflammatory cytokines in real time PCR; particularly TNF-α was significant lower (DSS+NI3 vs DSS; p = 0.013, DSS+NI30 vs DSS; p = 0.003). In Western blot assay, there was no difference in NF-κB, p-NF-κB were significantly decreased in NI treated group. iNOS was also reduced in NI treated group. iNOS and HMGB1 was decreased in immunohistochemical staining. Conclusion: Necrosis inhibitor improved DSS induced chronic colitis by decreasing mRNA expression of pro-inflammatory cytokines such as TNF-α. Necrosis inhibitor can be a novel treatment approach in IBD.
more목차
I. Introduction..............................................1
II. Materials and Methods.............................3
III. Results.....................................................8
IV. Discussion and Conclusion......................11
V. Figures and Tables...................................14
VI. References.............................................27
VII. Abstract................................................33
