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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 劉興華 | zh_TW |
| dc.contributor.advisor | Shing-Hwa Liu | en |
| dc.contributor.author | 林振宇 | zh_TW |
| dc.contributor.author | Chen-Yu Lin | en |
| dc.date.accessioned | 2024-02-22T16:53:07Z | - |
| dc.date.available | 2024-02-23 | - |
| dc.date.copyright | 2024-02-22 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-02-01 | - |
| dc.identifier.citation | Asada, N., M. Takase, J. Nakamura, A. Oguchi, M. Asada, N. Suzuki, K. Yamamura, N. Nagoshi, S. Shibata, T. N. Rao, H. J. Fehling, A. Fukatsu, N. Minegishi, T. Kita, T. Kimura, H. Okano, M. Yamamoto, and M. Yanagita. 2011. ''Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice'', J Clin Invest, 121: 3981-90.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/91823 | - |
| dc.description.abstract | 低強度脈衝超音波（Low-intensity pulsed ultrasound, LIPUS）是一種治療超音波，可以幫助改善骨折修復及使組織癒合。在本研究中，我們分別使用單側腎缺血/再灌流損傷（ischemia/reperfusion injury, IRI）、對側腎切除術和腺嘌呤(adenine)給藥等兩種小鼠模式來誘導慢性腎病變(chronic kidney disease, CKD)。接著使用LIPUS以3MHz、100mW/cm2、20分鐘/天的條件自第1天治療CKD小鼠的左腎，並在IRI後14天或腺嘌呤每日給藥(50mg/kg)後28天對小鼠進行安樂死。由實驗結果可知，LIPUS治療顯著降低了兩種CKD模式小鼠的血清BUN/肌酸酐水平，也減緩體重、握力、肌肉重量、白蛋白/球蛋白比值、肌纖維橫截面積的下降。而且經由CKD小鼠的免疫組織化學(immunohistochemistry)與西方墨點法(Western blot)分析結果可知肌肉磷酸化Akt蛋白表達下降、肌肉萎縮基因(atrogenes)相關蛋白(Atrogin-1和MuRF1)表達增加、纖維母細胞生長因子23 (FGF23)、腎臟病理變化和腎纖維化的蛋白表達增加。此外LIPUS治療顯著減輕了CKD小鼠腎臟內的上皮間質轉化(epithelial-mesenchymal transition, EMT)參數、衰老相關信號誘導以及α-Klotho和內源性抗氧化酶蛋白表達的抑制。以上結果證實LIPUS能透過抑制EMT和老化相關訊號來減緩CKD，並改善肌肉力量減弱、肌肉質量損失、肌肉萎縮相關蛋白表達和Akt失活。 | zh_TW |
| dc.description.abstract | Low-intensity pulsed ultrasound (LIPUS) is a type of therapeutic ultrasound that can help improve fracture repair and tissue healing. In this study, we used two mouse models: unilateral renal ischemia/reperfusion injury (IRI) with contralateral nephrectomy, and adenine administration to induce chronic kidney disease (CKD). Then LIPUS was used to treat the left kidney of CKD mice from day 1 at 3MHz, 100mW/cm2, 20 minutes/day, and the mice were euthanized 14 days after IRI or 28 days after daily administration of adenine (50mg/kg). It can be seen from the experimental results that LIPUS treatment significantly reduced the serum BUN/creatinine levels of two CKD model mice, and also slowed the decrease in body weight, grip strength, muscle weight, albumin/globulin ratio, and muscle fiber cross-sectional area. Moreover, the results of immunohistochemistry and Western blot analysis of CKD mice showed that the expression of muscle phosphorylated Akt protein decreased, the expression of muscle atrophy gene (atrogenes)-related proteins (Atrogin-1 and MuRF1) increased, and the expression of muscle fiber increased protein expression of blast growth factor 23 (FGF23), renal pathological changes, and renal fibrosis. In addition, LIPUS treatment significantly alleviated epithelial-mesenchymal transition (EMT) parameters, induction of aging-related signals, and inhibition of α-Klotho and endogenous antioxidant enzyme protein expression in the kidneys of CKD mice. The above results show that LIPUS can slow down CKD by inhibiting EMT and aging-related signals, and improve muscle strength weakening, muscle mass loss, muscle atrophy-related protein expression and Akt inactivation. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-02-22T16:53:06Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-02-22T16:53:07Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 誌謝 I
中文摘要 II Abstract III 縮寫清單 XI 第壹章 緒論 1 第一節 慢性腎臟病(CKD)目前的發展與影響 1 第二節 慢性腎臟病造成的肌肉減少症(Sarcopenia) 5 第三節 低強度脈衝超音波(LIPUS)治療 8 第四節 缺血/再灌流損傷(IRI) 8 第五節 餵食腺嘌呤(Adenine)誘導CKD 9 第六節 研究目標 11 第貳章 材料與方法 12 第一節 動物和實驗方案 12 第二節 IRI誘導的CKD模型 12 第三節 腺嘌呤誘導的CKD模型 13 第四節 LIPUS治療 13 第五節 血清生化分析 14 第六節 血清硫酸吲哚酚(IS)的檢測 14 第七節 握力測試 14 第八節 組織學分析 15 第九節 免疫印跡(Immunoblotting) 15 第十節 即時定量PCR (qPCR) 16 第十一節 統計分析 17 第參章 結果與討論 18 第一節 LIPUS治療能減輕IRI或腺嘌呤誘導的CKD小鼠模型的體重、血清生化值和腎損傷的變化 18 (一) 結果 18 1. LIPUS減輕IRI誘導的CKD小鼠模型的體重、血清生化值和腎損傷的變化 18 2. LIPUS減輕腺嘌呤誘導的CKD小鼠模型的體重、血清生化值和腎損傷的變化 19 (二) 討論 20 第二節 LIPUS治療能減緩IRI或腺嘌呤誘導的CKD小鼠模型的肌肉流失、肌肉膠原沉積和肌肉萎縮的變化 25 (一) 結果 25 1. LIPUS對兩種CKD小鼠模型的體重、腎功能標記、握力和肌肉重量的影響 25 2. LIPUS對兩種CKD小鼠模型中肌纖維橫截面積(CSA)和分佈以及肌肉膠原沉積的影響 25 3. LIPUS對兩種CKD小鼠模型中肌肉消耗/萎縮相關訊號分子Akt和atrogen的影響 26 (二) 討論 26 第肆章 結論與未來展望 29 結果圖 30 參考文獻 64 附錄 75 | - |
| dc.language.iso | zh_TW | - |
| dc.title | 探討治療性超音波治療慢性腎病及肌肉萎縮透過調節腎上皮間質轉化和老化相關蛋白的機制 | zh_TW |
| dc.title | Explore the mechanism of therapeutic ultrasound to treatment chronic kidney disease and muscle atrophy by regulating related proteins from renal epithelial to mesenchymal transition and senescence. | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-1 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 許美玲;姜至剛;藍國徵;吳鎮天 | zh_TW |
| dc.contributor.oralexamcommittee | Meei-Ling Sheu;Chih-Kang Chiang;Kuo-Cheng Lan;Cheng-Tien Wu | en |
| dc.subject.keyword | 低強度脈衝超音波,缺血/再灌流損傷,腺嘌呤,慢性腎病變,腎纖維化,上皮間質轉化,老化,肌肉減少症, | zh_TW |
| dc.subject.keyword | Low-intensity pulsed ultrasound,Ischemia/reperfusion injury,Adenine,Chronic kidney disease,Renal fibrosis,Epithelial-mesenchymal transition,Senescence,Sarcopenia, | en |
| dc.relation.page | 75 | - |
| dc.identifier.doi | 10.6342/NTU202400377 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2024-02-01 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 毒理學研究所 | - |
| 顯示於系所單位： | 毒理學研究所 | |
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