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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 游偉絢(Wei-Hsuan Yu) | |
| dc.contributor.author | Ya-Ting Yang | en |
| dc.contributor.author | 楊雅婷 | zh_TW |
| dc.date.accessioned | 2021-06-08T00:45:03Z | - |
| dc.date.copyright | 2020-08-27 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-17 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17866 | - |
| dc.description.abstract | 腸道發炎是潰瘍性結腸炎 (ulcerative colitis) 一個典型的病徵，臨床上潰瘍性結腸 炎的治療常以抑制腸道內異常發炎反應作為治療方針。白頭翁湯 (Pulsatilla decoction) 為一傳統中藥，也是亞洲國家中醫師用以治療潰瘍性結腸炎的處方之一， 然而目前尚不清楚白頭翁湯是透過何種機制抑制腸道發炎。因此，本篇論文中， 我們將葡萄糖硫酸鈉 (dextran sulfate sodium) 添加至小鼠的飲用水誘發潰瘍性結腸 炎，並且餵予小鼠白頭翁湯，探討其在潰瘍性結腸炎小鼠模型中的分子機制。我 們發現在餵予小鼠白頭翁湯後，會有較少的先天免疫細胞浸潤到大腸，使得腸道 發炎的現象較為趨緩。並且，在潰瘍性結腸炎小鼠模型中，嗜中性白血球與巨噬 細胞浸潤的程度與促發炎細胞激素介白素-1β 與腫瘤壞死因子-α 的量呈現正相關。 在免疫螢光染色實驗中，我們進一步觀察到腸道中浸潤的白血球與巨噬細胞會表 現基質金屬蛋白酶-7 (matrix metalloproteinase-7, MMP-7) 。有趣的是，當白頭翁湯 減少腸道中嗜中性白血球與巨噬細胞的浸潤時，活化型 MMP-7 的蛋白表現量也會 隨之下降，顯示在潰瘍性結腸炎小鼠模型中，白頭翁湯由 MMP-7 調控免疫細胞聚 集的重要性。整體來說，我們的研究提供白頭翁湯在抑制人類潰瘍性結腸炎中可 能參與的一種分子機制，並且指出抑制 MMP-7 可能可以作為潰瘍性結腸炎一有效 的治療方針。 | zh_TW |
| dc.description.abstract | Intestinal inflammation is considered to be an important characteristic of ulcerative colitis (UC) and the current medical treatments of UC are usually proposed to suppress abnormal intestinal immune responses. Pulsatilla decoction (PD), a traditional Chinese medicine, is frequently used in UC treatments in Asian countries; however, the mechanism of the action of PD remains unclear. In the present study, the mechanism of the action of PD is elucidated in dextran sulfate sodium (DSS)-induced colitis mouse model. In DSS-induced colitis mouse model, the administration of PD attenuates the intestinal inflammation through suppression of colonic infiltration of innate immune cells. In addition, the level of neutrophil and macrophage infiltration is consistent with the level of pro-inflammatory cytokines, interleukin-1β and tumor necrosis factor-α, in colonic tissues in DSS-induced colitis mouse model. The immunofluorescence double staining further reveals that matrix metalloproteinase-7 (MMP-7) is expressed by the infiltrating leukocytes, including macrophages. Noticeably, the reduced neutrophil and macrophage infiltration is accompanied by a downregulation of the protein level of active MMP-7 in PD treatments, which identifies MMP-7 as an important regulator of leukocyte recruitment in intestinal inflammation underlying PD in DSS-induced colitis mouse model. In conclusion, these findings provide a potential molecular mechanism underlying PD in UC and indicate MMP-7 inhibition as a promising therapeutic approach in UC therapy. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T00:45:03Z (GMT). No. of bitstreams: 1 U0001-1408202000195400.pdf: 4306051 bytes, checksum: 7a91c2d332ed5e827eee34a7cf1c6165 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 致謝 .............................................................................i 中文摘要 .........................................................................ii Abstract .........................................................................iii Table of Contents ................................................................iv List of Figures...................................................................vii List of Tables ...................................................................ix Chapter 1. Introduction ..........................................................1 1.1 Inflammatory bowel disease ...................................................1 1.2. Dextran sulfate sodium-induced colitis mouse model ..........................1 1.2.1. Molecular mechanism in DSS-induced colitis mouse model ....................2 1.3. Matrix metalloproteinases-7..................................................3 1.3.1. Matrix metalloproteinase-7 in immunity ....................................4 1.3.2. Matrix metalloproteinase-7 in ulcerative colitis...........................4 1.4. Treatments for ulcerative colitis ...........................................5 1.4.1. Pulsatilla decoction in traditional Chinese medicine ......................6 Chapter 2. Specific Aims..........................................................7 2.1. To investigate the role of matrix metalloproteinase-7 (MMP-7) upon dextran sulfate sodium (DSS) exposure in vitro and in vivo .....7 2.1.1. To address whether DSS induce MMP-7 expression and activation in HT-29, Caco-2, and Raw 264.7 cells .............................7 2.1.2. To address whether DSS induce MMP-7 expression and activation in DSS-induced colitis mouse model ................................7 2.2. To investigate the therapeutic effects of Pulsatilla decoction (PD) on DSS- induced colitis mouse model ...........................8 2.2.1. To address whether PD ameliorates DSS-induced murine colitis ..............8 2.2.2. To address whether PD suppresses intestinal inflammation in DSS- induced colitis mouse model ....................................9 2.2.3. To address whether PD suppresses changes in intestinal architecture in DSS-induced colitis mouse model ..........................10 Chapter 3. Materials and Methods..................................................11 3.1. Mice ........................................................................11 3.2. Cell lines and cell culture..................................................11 3.3. Cell viability assay ........................................................12 3.4. DSS-induced colitis mouse models.............................................12 3.4.1. Preparation of Pulsatilla decoction........................................13 3.5. Assessment of colitis .......................................................13 3.6. Histopathological analysis ..................................................14 3.7. Immunohistochemical (IHC) analysis ..........................................16 3.8. Immunoblot analysis .........................................................17 3.9. Multi-Plex immunoassay ......................................................18 3.10. Immunofluorescence staining.................................................18 3.11. Statistical analysis .......................................................19 Chapter 4. Results ...............................................................20 4.1. DSS exhibits cytotoxic effects on Caco-2 and Raw 264.7 cells and induces MMP-7 activation in vitro..................................20 4.2. Pulsatilla decoction (PD) ameliorates DSS-induced colitis mouse model ......20 4.3. PD reduces the infiltration of Ly6G+ neutrophils and F4/80+ macrophages in colonic inflammation.....................................22 4.4. PD increases the cytokine level of IL-6 in colonic tissues in DSS-induced colitis mouse model.......................................23 4.5. PD does not significantly increase the epithelial proliferation in DSS-induced colitis mouse model..................................24 4.6. DSS alters the localization of MMP-7 from intestinal epithelial cells to infiltrating immune cells..................................25 4.7. PD decreases the activation of MMP-7 and suppresses MMP-7+ infiltrating immune cells in DSS-induced colitis mouse model.............26 4.8. DSS increases the activation of MMP-7 in the proximal colon with a time dependency in DSS-induced colitis mouse model by western blot analysis .........27 4.9. MMP-7 regulates the colonic infiltration of neutrophils and macrophages through increasing cytokine levels of IL-1β and TNF-α while PD inhibits MMP- 7-mediated neutrophil and macrophage infiltration in DSS-induced colitis mouse model.....28 Chapter 5. Discussion.............................................................30 Chapter 6. Reference..............................................................35 Chapter 7. Figures................................................................44 | |
| dc.language.iso | en | |
| dc.title | 在潰瘍性結腸炎小鼠模型中探討白頭翁湯的分子機制 | zh_TW |
| dc.title | Investigation of the molecular mechanism underlying the Pulsatilla decoction in dextran sulfate sodium-induced colitis mouse model | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳煥源(Huan-Yuan Chen),俞松良(Sung-Liang Yu) | |
| dc.subject.keyword | 基質金屬蛋白酶-7,白頭翁湯,免疫細胞聚集,腸道發炎,潰瘍性結腸炎, | zh_TW |
| dc.subject.keyword | Matrix metalloproteinase-7,Pulsatilla decoction,leukocyte recruitment,intestinal inflammation,ulcerative colitis, | en |
| dc.relation.page | 64 | |
| dc.identifier.doi | 10.6342/NTU202003348 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2020-08-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
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