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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 劉興華(Shing-Hwa Liu) | |
| dc.contributor.author | Jui Zhi Loh | en |
| dc.contributor.author | 駱瑞芝 | zh_TW |
| dc.date.accessioned | 2021-06-17T04:50:14Z | - |
| dc.date.available | 2018-08-30 | |
| dc.date.copyright | 2018-08-30 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-07-31 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71046 | - |
| dc.description.abstract | 急性腎損傷 (acute kidney injury, AKI)大多由缺血再灌流 (ischemia-reperfusion)造成, 通常發生在病人進行腎臟移植或者大型手術的時候, 還有患者敗血症併發AKI。AKI是臨床上常見問題, 特性為病人腎功能突然減少，通常在數小時至幾週內發生， AKI與病人死亡率提高有著密切的關係。大部分的AKI病人由於腎臟無法修復完整而發展成慢性腎疾病 (chronic kidney disease, CKD)，以至於病人生命受到更大的威脅。低強度脈衝超音波 (Low intensity pulsed ultrasound, LIPUS) 是運用在臨床治療骨折的儀器。LIPUS 有著加速骨頭修復過程以及幫助其他軟組織如軟骨，心臟等修復的功效，但目前LIPUS運用在幫助腎損傷的修復尚未被驗證。因此，本篇研究主要想探討LIPUS對於腎損傷所帶來的保護功用。首先，我們摘除C57BL/6J公鼠單側腎臟，一周後再對僅存的腎臟進行缺血再灌流傷害(ischemia-reperfusion injury, IRI)。我們在摘除單側腎臟後的第二天開始每天給予小鼠LIPUS預防治療直到小鼠接受IRI誘導。IRI誘導後小鼠將每天接受LIPUS持續治療直到犧牲為止。IRI誘導 24小時後犧牲小鼠作為AKI模式而IRI 誘導30天後犧牲為CKD模式。小鼠的血液、腎臟及骨頭將被收集以進行後續分析。在偵測血清生化指標時，我們發現AKI模式小鼠血清中cystatin C以及CKD模式小鼠serum creatinine（SCr）在IRI後皆提升，但在LIPUS處理情況下這些數值明顯下降。此外，透過Periodic-Acid Schiff (PAS) 染色觀察腎臟病理組織切片時發現CKD模式中IRI+LIPUS組別小鼠腎損傷的情形比IRI組別輕微。接著，western blot結果顯示，LIPUS有效降低由IRI所誘導提升的CHOP以及cleaved-caspase 3的蛋白表現量，說明腎臟內質網壓力（endoplasmic-reticulum(ER) stress）及細胞凋亡減少的趨勢。LIPUS還顯著復原由IRI誘導下降的抗氧化酶如catalase的蛋白表現量。此外，在觀察老化相關marker（p53、p21及p16）時發現IRI會大量提升這些marker的蛋白表現量，然而LIPUS處理則逆轉這些現象。再來，透過Masson’s Trichrome染色評估腎纖維化程度以及觀察纖維化marker，α-SMA時得出LIPUS有效於降低腎纖維化的結論。最後，我們還發現CKD模式中小鼠在接受IRI後血清FGF23的濃度明顯上升，但在IRI+LIPUS組別中並未得到相同結果。綜合上述結果，我們研究指出LIPUS有治療腎損傷的效果，而這些效果是透過減少腎臟內質網壓力，細胞凋亡，復原antioxidant enzymes，以及延遲腎老化及腎纖維化。因此，LIPUS有潛力作為減輕腎損傷以及延緩CKD發展的預防治療方式。 | zh_TW |
| dc.description.abstract | Ischemia/reperfusion contributed to most cases of acute kidney injury (AKI), it commonly occurs during kidney transplantation, other major surgery or sepsis. AKI is a severe clinical issue, characterized by kidney damage with a rapid decline of renal function, and strongly associated with high mortality rates. Majority of AKI patients progress to chronic kidney disease (CKD) due to incomplete recovery of AKI further increase the mortality rates in patients. Low intensity pulsed ultrasound (LIPUS) has been recognized to accelerate bone fracture repair process and help in some soft tissues healing such as cartilage and cardiac tissues. However, the effect of LIPUS on renal injury treatment is yet to be investigated. Hence, we aimed to testify the therapeutic effect of LIPUS on renal injury. First, one week before ischemia/reperfusion injury (IRI), we performed unilateral nephrectomy on C57BL/6J male mice, followed by pre-treatment of LIPUS on day 2 after unilateral nephrectomy. IRI surgery was done one week after unilateral nephrectomy, LIPUS treatment was continued started from the day after IRI, once per day until the day of euthanization. Mice sacrificed 24 hours after IRI was considered as AKI model and 30 days after IRI as CKD model. Serum, kidney and bone were harvested for further analysis. By detecting serum biochemical parameter, we observed markedly increase in cystatin C in AKI model and serum creatinine in CKD model after IRI, however, the increase was reduced with LIPUS treatment. Pathological changes of renal tissues was observed using Periodic-Acid Schiff (PAS) stain, results showed less renal injury in IRI+LIPUS group compared to IRI group in CKD model. Besides, with western blot results, we noticed the effect of LIPUS on reducing IRI-induced CHOP and cleaved-caspase 3 expression, implicating decrease in endoplasmic-reticulum(ER) stress, apoptosis and restoring antioxidant enzymes levels such as catalase in AKI and CKD model. Furthermore, the aging markers (p53, p21 and p16) were induced after IRI in CKD model, in contrast LIPUS treatment reversed the situation. We also noted delayed renal fibrosis after IRI with LIPUS treatment by evaluating the fibrosis area on Masson’s Trichrome stained tissue sections and protein expression level of fibrotic marker, α-SMA. Finally, results showed increase of serum FGF23 after IRI declined after LIPUS treatment in CKD model. In short, LIPUS treatment has been demonstrated in our study to exert protective effect on renal injury by attenuating ER stress, apoptosis, restoring antioxidant enzymes, delaying renal aging and renal fibrosis. Therefore, LIPUS could serve as early intervention to reduce renal injury and delay CKD progression. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T04:50:14Z (GMT). No. of bitstreams: 1 ntu-107-R05447012-1.pdf: 2415907 bytes, checksum: 9fc10f9931586e79dec35f9538891aea (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 誌謝 I
中文摘要 III Abstract V Abbreviation Summary VII Part I: Introduction 1 1.1 Ischemia/Reperfusion Injury (IRI)-induced Renal Injury 1 1.2 Cellular Pathophysiology of Ischemic AKI 2 1.2.1 Apoptosis 2 1.2.2 Endoplasmic Reticulum (ER) Stress 4 1.2.3 Antioxidant Enzymes 5 1.2.4 Autophagy 6 1.3 Progression of AKI to CKD 7 1.3.1 Fibrosis 7 1.3.2 Aging 8 1.4 CKD–associated Mineral and Bone Disorder (CKD–MBD) 9 1.5 Low Intensity Pulsed Ultrasound (LIPUS) as a Therapeutic Device 10 Part II: Aim 12 Part III: Materials and Methods 13 3.1 Animals 13 3.2 Design and procedures of animal experiments 13 3.3 LIPUS therapy 14 3.4 Serum biochemical parameters measurement 14 3.5 Pathological observation of the kidney 14 3.6 Histological examination of bone tissues 15 3.7 Caspase 3 activity in renal tissues 15 3.8 Western blotting 15 3.9 Statistics 16 Part IV: Results 19 4.1 LIPUS reduced IRI-induced tubular injury in CKD model 19 4.2 LIPUS diminished renal ER stress and apoptosis after IRI 19 4.3 IRI-induced decrease levels of antioxidant enzymes was rescued after LIPUS treatment 20 4.4 The beneficial effect of LIPUS on autophagy after IRI was not significant 20 4.5 LIPUS may attenuate renal aging and delay renal fibrosis 21 4.6 LIPUS reduced serum FGF23 in CKD model 22 Part V: Discussion 23 Part VI: Conclusion 28 Part VII: References 29 Part VIII: Figures and Figure Legends 40 Figure 1. The effect of LIPUS on serum biochemical parameters in mice with AKI or CKD. 40 41 Figure 2. The effect of LIPUS on IRI-induced renal tubular injury in AKI model. 41 Figure 3. The effect of LIPUS on CKD-related renal tubular injury. 42 Figure 4. The effect of LIPUS on renal ER stress and apoptosis-related signals in an AKI model. 43 44 Figure 5. The effect of LIPUS on renal ER stress and apoptosis-related signals in a CKD model. 44 Figure 6. Elevation of renal antioxidant enzymes levels after LIPUS treatment in both AKI model. 46 47 Figure 7. Elevation of renal antioxidant enzymes levels after LIPUS treatment in CKD model. 47 Figure 8. The effect of LIPUS on renal autophagy-related signals in both AKI and CKD models. 48 Figure 9. The effect of LIPUS on renal senescence-related signals in a CKD model. 50 Figure 10. LIPUS reduces renal fibrosis in a CKD model. 51 Figure 11. The effects of LIPUS on serum FGF23 levels and bone microstructure in a CKD model. 53 | |
| dc.language.iso | en | |
| dc.subject | 抗氧化? | zh_TW |
| dc.subject | 急性腎損傷 | zh_TW |
| dc.subject | 慢性腎疾病 | zh_TW |
| dc.subject | 老化 | zh_TW |
| dc.subject | 腎纖維化 | zh_TW |
| dc.subject | 低強度脈衝超音波 | zh_TW |
| dc.subject | 缺血再灌流 | zh_TW |
| dc.subject | 內質網壓力 | zh_TW |
| dc.subject | renal fibrosis | en |
| dc.subject | aging | en |
| dc.subject | antioxidant enzymes | en |
| dc.subject | endoplasmic-reticulum stress | en |
| dc.subject | low intensity pulsed ultrasound | en |
| dc.subject | chronic kidney disease | en |
| dc.subject | acute kidney injury | en |
| dc.subject | Ischemia/reperfusion | en |
| dc.title | 低強度脈衝超音波對於腎臟缺血再灌流所致傷害的保護效果 | zh_TW |
| dc.title | The Protective Effect of Low Intensity Pulsed Ultrasound on Renal Ischemia/Reperfusion Injury | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 姜至剛(Chih-Kang Chiang),楊榮森(Rong-Sen Yang),許美鈴(Meei-Ling Sheu),蕭水銀(Shoei-Yn Lin-Shiau) | |
| dc.subject.keyword | 缺血再灌流,急性腎損傷,慢性腎疾病,低強度脈衝超音波,內質網壓力,抗氧化?,老化,腎纖維化, | zh_TW |
| dc.subject.keyword | Ischemia/reperfusion,acute kidney injury,chronic kidney disease,low intensity pulsed ultrasound,endoplasmic-reticulum stress,antioxidant enzymes,aging,renal fibrosis, | en |
| dc.relation.page | 53 | |
| dc.identifier.doi | 10.6342/NTU201802244 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-07-31 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 毒理學研究所 | zh_TW |
| 顯示於系所單位： | 毒理學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-107-1.pdf 未授權公開取用 | 2.36 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。