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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 黃德富(Tur-Fu Huang) | |
dc.contributor.author | Jian-Bang Lin | en |
dc.contributor.author | 林健邦 | zh_TW |
dc.date.accessioned | 2021-06-13T15:23:37Z | - |
dc.date.available | 2008-08-08 | |
dc.date.copyright | 2008-08-08 | |
dc.date.issued | 2008 | |
dc.date.submitted | 2008-07-22 | |
dc.identifier.citation | Andrews, R.K. and M.C. Berndt, 2004, Platelet physiology and thrombosis, Thromb Res 114, 447.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37294 | - |
dc.description.abstract | 利用 CM-Sephadex C-50 柱層層析與高效液相層析法分離純化出眼鏡蛇蛇毒 (Naja naja atra venom,NNAV) 中的心臟毒素 A3 (cardiotoxin A3,CTX A3),本實驗探討其在血小板凝集以及血管新生方面的作用。
單獨地使用 CTX A3 無法引發血小板凝集 (14.84 μM),然而可以依照濃度相關性地促進 collagen 所誘發的血小板凝集反應 (0.74 ~ 3 μM),並且在該濃度下隨濃度增加有促進 thromboxane A2 生合成的作用。 在流式細胞儀的分析下,CTX A3 不會影響人類臍靜脈內皮細胞與單株抗體 anti-β1、αv、αvβ3、αvβ5、α6、α5β1、7E3 結合,而外加 heparin 則會減少 CTX A3 與細胞結合。CTX A3 隨著濃度增加會使內皮細胞 sub-G1 相、annexin V 染色增加,並在 TUNEL 實驗中觀察到其對細胞造成的凋亡現象。CTX A3 可依濃度相關性顯著地抑制內皮細胞移行 (0.74 ~ 3 μM);而且在免疫螢光染色下可觀察到 CTX A3 會抑制細胞應力纖維 (stress fiber) 的形成,但 CTX A3 只輕微抑制細胞與細胞外基質 fibronectin、fibrinogen 和 collagen 結合。CTX A3 也會抑制內皮細胞在 matrigel 所誘發的管狀生成,於 0.74 μM 即達到最大抑制效果 (約 20%,濃度在 0.74 ~ 3 μM 之間)。 綜合來說,CTX A3 可以促進 collagen 所引發 thromboxane A2 生合成和血小板凝集,並且依濃度相關性地誘發人類臍靜脈內皮細胞凋亡,在功能上,CTX A3 會抑制應力纖維形成、細胞移行以及內皮細胞管狀生成;然而,在抗血管新生之範疇中,CTX A3的應用性可能會受其細胞毒性所限制。 | zh_TW |
dc.description.abstract | By using column chromatography of CM-Sephadex C-50 and high performance liquid chromatography, cardiotoxin A3 (CTX A3) was purified from Naja naja atra venom. In this paper, we investigated the effects of CTX A3 on platelet aggregation and angiogenesis in HUVECs.
CTX A3 potentiated collagen-triggered platelet aggregation of washed human platelets in a concentration-dependent manner (0.74 ~ 3 μM) accompanied with the enhancement of thromboxane A2 biosynthesis. However, CTX A3 did not induce platelet aggregation by itself (14.84 μM). On the other hand, it did not affect the binding of anti-β1, αv, αvβ3, αvβ5, α6, α5β1 or 7E3 monoclonal antibody to HUVECs, however its binding to HUVECs was decreased upon heparin treatment. CTX A3 induced apoptosis in a concentration-dependent manner as evidenced by the increased sub-G1 phase, annexin V staining and TUNEL assay. CTX A3 significantly inhibited HUVECs migration in a concentration-dependent manner (0.74 ~ 3 μM). Furthermore, the stress fiber formation of endothelial cells was also significantly impaired by CTX A3. CTX A3 only slightly inhibited adhesion of HUVECs to extracellular matrics (ECM), e.g. fibronectin, fibrinogen and collagen. It also inhibited matrigel-induced HUVECs tube formation with maximal inhibition (20%) at 0.74 μM. In conclusion, CTX A3 potentiates collagen-triggered platelet aggregation accompanied with enhancement of thromboxane A2 biosynthesis. It induces apoptosis of HUVECs in a concentration-denpendent manner. Functionally, it impairs stress fiber formation, migration and also capillary tube formation. However, its cytotoxic activity may limit its application in the field of anti-angiogenesis therapy. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T15:23:37Z (GMT). No. of bitstreams: 1 ntu-97-R95443007-1.pdf: 3592862 bytes, checksum: f5c1e7a979067ffb8b6512d7dc3e6f9b (MD5) Previous issue date: 2008 | en |
dc.description.tableofcontents | 口試委員會審定書 i
致謝 ii 中文摘要 iii 英文摘要 v 縮寫表 vii 第一章 緒論 1 1.1 血管新生 1 1.2 細胞凋亡 3 1.3 血小板凝集 4 1.4 心臟毒素 5 第二章 實驗材料 15 第三章 實驗方法 17 第四章 結果 32 4.1 眼鏡蛇心臟蛇毒蛋白的純化與篩選 32 4.2 蛇毒蛋白 CTX A3 的純度與鑑定 33 4.3 蛇毒蛋白 CTX A3 對人類血小板懸浮液凝集作用的影響 34 4.4 蛇毒蛋白 CTX A3 對 thromboxane B2 生成的影響 34 4.5 蛇毒蛋白 CTX A3 與人類臍靜脈內皮細胞之結合試驗 35 4.6 蛇毒蛋白 CTX A3 抑制內皮細胞附著到胞外基質 (ECM) 36 4.7 蛇毒蛋白 CTX A3 影響內皮細胞的存活 37 4.8 蛇毒蛋白 CTX A3 抑制內皮細胞的移行作用 39 4.9 蛇毒蛋白 CTX A3 抑制 matrigel 引發 HUVEC 管狀結構生成40 第五章 討論 69 第六章 結論與未來展望 76 參考文獻 77 | |
dc.language.iso | zh-TW | |
dc.title | 蛇毒蛋白cardiotoxin A3影響血小板凝集與血管新生的探討 | zh_TW |
dc.title | The effects of cardiotoxin A3 on platelet aggregation and angiogenesis | en |
dc.type | Thesis | |
dc.date.schoolyear | 96-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 鄧哲明(Che-Ming Teng),顏茂雄(Mao-Hsiung Yen),楊春茂(Chuen-Mao Yang) | |
dc.subject.keyword | 心臟毒素,血小板凝集,內皮細胞凋亡,移行,血管新生, | zh_TW |
dc.subject.keyword | cardiotoxin,platelet aggregation,apoptosis of endothelial cells,migration,angiogenesis, | en |
dc.relation.page | 81 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2008-07-22 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥理學研究所 | zh_TW |
顯示於系所單位: | 藥理學科所 |
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