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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張以承(Yi-Cheng Chang) | |
| dc.contributor.author | Tung-Yuan Lee | en |
| dc.contributor.author | 李東原 | zh_TW |
| dc.date.accessioned | 2022-11-25T03:03:28Z | - |
| dc.date.available | 2026-08-25 | |
| dc.date.copyright | 2021-09-16 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-25 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81781 | - |
| dc.description.abstract | 急性腎損傷，是常見疾病，全世界每年約有1300萬的病患，其中甚至有170萬導致死亡，致病原因有失血、大量缺血、敗血症、尿路阻塞、腎毒性物質。順鉑（cisplatin），為一種常用癌症化學治療藥物，但卻具腎毒性。 在腎臟中，順鉑透過進入腎小管上皮細胞，與核酸的鹼基結合，導致細胞下游的凋亡機制啟動，腎小管上皮細胞也可釋放TNF-ɑ引發發炎反應，最終都將導致細胞死亡，腎絲球過濾率下降，引發急性腎損傷。過去文獻中發現順鉑誘發之急性腎損傷，也會導致腎小管上皮細胞的氧化壓力提高，包含細胞膜脂肪酸過氧化生成的有毒醛類4-hydroxynonenal （4-HNE）含量上升，4-HNE具有高生物反應活性，可以和核酸結合導致雙股斷裂，也可以和蛋白質結合修飾造成功能缺損。此外，在急性腎損傷的腎小管上皮細胞也發現有粒線體機能與能量代謝能力受損的情況。 Acetaldehyde dehydrogenase 2 （ALDH2）是位於粒線體中負責代謝醛類的酵素。AD-9308，是一個具有高度專一性新型水溶性ALDH2促進劑，可以改善原先酵素活性的缺損，降低4-HNE含量，並促進能量代謝。本篇研究建立順鉑誘發之急性腎損傷小鼠模式，發現給予AD-9308可以減緩腎臟損傷，改善腎功能與提高小鼠存活率，提高ALDH2酵素活性並降低4-HNE含量與氧化壓力、減少細胞凋亡路徑的活化、改善粒線體的缺損。急性腎損傷目前的治療主要是支持性治療，無有效治療，本研究利用活化ALDH2減緩急性腎損傷，提供順鉑誘發之急性腎損傷治療上的契機。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T03:03:28Z (GMT). No. of bitstreams: 1 U0001-2108202123492000.pdf: 15011026 bytes, checksum: 908ce16b446daa8ec1878483a4a937f8 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 口試委員審定書 i 誌謝 ii 中文摘要 iii ABSTRACT iv CONTENTS vi List of Figures viii List of Tables ix Chapter I ― Introduction 1 1. Pathophysiology of cisplatin-induced acute kidney injury (AKI) 1 2. Characteristics of Aldehyde dehydrogenase 2 (ALDH2) and application of its agonist 5 3. Properties of 4-Hydroxynonenal (4-HNE) 7 4. Renoprotective approaches and current treatments of cisplatin-induced AKI 8 5. Rationale of this study 9 Chapter II ― Materials and Methods 11 1. Animal model 11 2. Western blot analysis 11 3. IHC and HE stain 12 4. ALDH2 enzymatic activity assay 13 5. Mitochondria isolation 14 6. Mitochondrial respiratory chain complexes enzymatic activity assay 15 7. Serum biochemical parameters 15 8. 4-HNE measurement 15 9. Kidney injury markers measurement 16 10. Transmission electron microscopy (TEM) scanning 16 11. Cell culture and treatments 17 12. Statistics 17 Chapter III ― Results 18 1. Therapeutic effect of ALDH2 agonist AD-9308 on kidney-related phenotypes in cisplatin-AKI mice 18 2. AD-9308 alleviates renal tubule injury in cisplatin-AKI model 18 3. AD-9308 reduces apoptosis pathway activation in cisplatin-AKI model 19 4. AD-9308 enhances ALDH2 enzymatic activity and reduces the levels of 4-HNE in cisplatin-AKI mice 20 5. AD-9308 enhances mitochondrial functions in cisplatin-AKI mice 21 Chapter IV ― Discussion 23 FIGURES 27 REFERENCES 47 APPENDIX 53 | |
| dc.language.iso | en | |
| dc.subject | 粒線體 | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | 4-羥基壬烯醛 | zh_TW |
| dc.subject | 乙醛脫氫酶 | zh_TW |
| dc.subject | 急性腎損傷 | zh_TW |
| dc.subject | 順鉑 | zh_TW |
| dc.subject | apoptosis | en |
| dc.subject | mitochondria | en |
| dc.subject | ALDH2 | en |
| dc.subject | acute kidney injury | en |
| dc.subject | cisplatin | en |
| dc.subject | 4-HNE | en |
| dc.title | ALDH2促進劑AD-9308減緩順鉑誘發之小鼠急性腎損傷模式 | zh_TW |
| dc.title | "AD-9308, an ALDH2 agonist alleviates cisplatin-induced acute kidney injury in mice" | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.advisor-orcid | 張以承(0000-0002-8077-5011) | |
| dc.contributor.oralexamcommittee | 莊立民(Hsin-Tsai Liu),姜文智(Chih-Yang Tseng),黃祥博 | |
| dc.subject.keyword | 順鉑,急性腎損傷,乙醛脫氫酶,4-羥基壬烯醛,細胞凋亡,粒線體, | zh_TW |
| dc.subject.keyword | cisplatin,acute kidney injury,ALDH2,4-HNE,apoptosis,mitochondria, | en |
| dc.relation.page | 55 | |
| dc.identifier.doi | 10.6342/NTU202102576 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-08-25 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 基因體暨蛋白體醫學研究所 | zh_TW |
| dc.date.embargo-lift | 2026-08-25 | - |
| 顯示於系所單位： | 基因體暨蛋白體醫學研究所 | |
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