請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/91823
標題: | 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 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. |
作者: | 林振宇 Chen-Yu Lin |
指導教授: | 劉興華 Shing-Hwa Liu |
關鍵字: | 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, Low-intensity pulsed ultrasound,Ischemia/reperfusion injury,Adenine,Chronic kidney disease,Renal fibrosis,Epithelial-mesenchymal transition,Senescence,Sarcopenia, |
出版年 : | 2024 |
學位: | 博士 |
摘要: | 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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/91823 |
DOI: | 10.6342/NTU202400377 |
全文授權: | 未授權 |
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-112-1.pdf 目前未授權公開取用 | 5.07 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。