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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/24486完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 王淑美 | |
| dc.contributor.author | Meng-Ho Sung | en |
| dc.contributor.author | 宋孟河 | zh_TW |
| dc.date.accessioned | 2021-06-08T05:27:54Z | - |
| dc.date.copyright | 2011-10-07 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-07-28 | |
| dc.identifier.citation | United States Renal Data Systems. USRDS 2007 Annual Data Report: Atlas of End-
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/24486 | - |
| dc.description.abstract | 硫酸吲哚酚(Indoxyl sulfate)是屬於眾多尿毒素(Uremic toxin)其中一種。在人體中主要的來源是從飲食中所涉取的色氨酸(Tryptophan)在經由腸道細菌酵素代謝後經由血液運輸到肝臟成為硫酸吲哚酚。在血液中大約有90% 硫酸吲哚酚會與白蛋白結合形成較大的分子，因此在於慢性腎臟病變的病患，由於腎絲球過濾率的惡化造成硫酸吲哚酚無法被順利排出。高濃度的硫酸吲哚酚不僅會促進在慢性腎臟病變的惡化，更會透過血液系統去影響其他器官。比如說，目前有被指出在晚期慢性腎臟病變的病患大約有40-50%會因心臟方面的疾病而導致死亡。雖然有觀察到此現象，但並無太多的研究去探討硫酸吲哚酚對於心肌所造成的影響與其可能機制。因此本研究由觀察新生大鼠心肌細胞間隙接合去探討硫酸吲哚酚對於心肌的影響。在加入不同濃度硫酸吲哚酚處理後發現心肌並沒有任何凋亡或壞死。另外在正常組別心肌的connexin 43在細胞接合處的分佈多且大形成gap junction plaque。然而在硫酸吲哚酚處理後會使connexin 43在於心肌接合處染色分佈減少並gap junction plaque變小。硫酸吲哚酚對connexin 43所造成的影響也可在除藥後的24小時後回復，顯現出硫酸吲哚酚對於心肌影響具可逆性。在功能上使用scrape loading/dye transfer去評估細胞間隙接合溝通(GJIC)，發現硫酸吲哚酚會降低其細胞之間的溝通。而這個現象也反映在減緩的心肌跳動速率。其結果在使用免疫螢光染色中發後得到部分的解釋。在使用西方墨點分析法以及RT-PCR後也觀察到connexin 43整體蛋白與mRNA的表現下降。而這個現象卻可被(protein kinase C) PKC alpha和(c-jun NH¬2-terminal kinase) JNK的抑制劑所阻止，證明這兩個激酶在調控硫酸吲哚酚所造成connexin 43 影響上扮演著非常重要的角色。總結，硫酸吲哚酚會對心肌造成可逆性的功能下降,而其原因乃是因connexin 43會經由PKC alpha - JNK 訊息途徑活化後所造成的蛋白質和mRNA表現下降。進而導致細胞間隙接合缺陷無法形成具有功能性的通道。 | zh_TW |
| dc.description.abstract | Indoxyl sulfate is one of the numerous uremic toxins. Since 90% of indoxyl sulfate in the serum is bound to albumin, it is difficult for chronic kidney disease (CKD) patients to excrete it in urine. The difficulty is due to the deteriorated glomerular filtration rate in kidney of CKD patients. Accumulation of high concentration of indoxyl sulfate has not only been found to accelerate the progression of CKD, but also found to affect other organs via circulation system. For example, it has been suggested that 40-50% of death in end stage CKD patients are related cardiovascular diseases. However, despite the conspicuous awareness of this phenomenon, current knowledge on the correlation between CKD and CVD is still limited. Therefore, in order to elucidate the underlying effects of indoxyl sulfate on cardiomyocytes, this study was designed to investigate the molecular change of gap junction under indoxyl sulfate treatment. No cell death has been observed after indoxyl sulfate treatment, implying indoxyl sulfate does not affect cardiomyocyte survival. In addition, indoxyl sulfate induced reduction in total connexin43 level and the effects are reversible. Gap junction intercellular communication (GJIC) of cardiomyocyte was assessed with scrape loading and was found with reduced communication. Immunofluorescence staining showed the expression pattern and morphology of Cx43 was altered in indoxyl sulfate treated cardiomyocytes, which appeared to correlate with reduced Cx43 protein and mRNA expression. Inhibition of PKC alpha and JNK blocked indoxyl sulfate -induced down-regulation of Cx43 protein and mRNA expression. Furthermore, PKC alpha inhibition prevented the indoxyl sulfate induced JNK activation. Thus, the down regulation of Cx43 protein induced by indoxyl sulfate was mediated by the PKC alpha-JNK signaling cascade. The present study provides, for the first time, the effects of indoxyl sulfate on gap junction connexin43 in neonatal rat cardiomyocytes. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T05:27:54Z (GMT). No. of bitstreams: 1 ntu-100-R98446012-1.pdf: 2776485 bytes, checksum: 305c12526de78b2fd2ee23169b2905f2 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 誌謝……………………………………………………………………………………i
中文摘要………………………………………………………………………………ii ABSTRACT…………………………………………………………………………..iv CONTENTS………………………………………………………………………….vi LIST OF FIGURES………………………………………………………………….vii Chapter 1 Introduction…………………………………………………………...1 Chapter 2 Materials and Methods……………………………………………14 2.1 Primary cell culture of neonatal rat cardiomyocytes…………...………14 2.2 Measurement of cardiomyocytes contraction rate………………………15 2.3 DAPI and PI staining……………………………………………………16 2.4 MTT survival assay……………………………………………...………16 2.5 Antibodies and drugs……………………………………………………17 2.6 Drug Treatment…………………………………………………………..19 2.7 Immunofluorescence staining……………………………………………19 2.8 Scrape Loading/dye transfer (SL/DT)………………………………….19 2.9 Flow Cytometry analysis………………………………………………..20 2.10 Western blot analysis……………………………………………………..21 2.11 RNA extraction and RT-PCR…………………………………………23 2.12 Statistical analysis…………………………………….………………..25 Chapter 3 Results………………………………………………………………..26 Chapter 4 Discussion…………………………………………………………….35 REFERENCES…………………………………………………………………….41 Chapter 5 Figures and Tables…………………………………………………...47 Supplement ……………………………………………………………………….66 LIST OF FIGURES Fig 5.1……….………………………………………………………………………..47 Fig 5.2…….…………………………………………………………………………..48 Fig 5.3….……………………………………………………………………………..49 Fig 5.4…….…………………………………………………………………………..50 Fig 5.5……….………………………………………………………………………..51 Fig 5.6.………………………………………………………………………………..52 Fig 5.7.………………………………………………………………………………..53 Fig 5.8.………………………………………………………………………………..54 Fig 5.9………………………………………………………………………………...55 Fig 5.10……………………………………………………………………………….56 Fig 5.11……………………………………………………………………………….57 Fig 5.12……………………………………………………………………………….58 Fig 5.13……………………………………………………………………………….59 Fig 5.14……………………………………………………………………………….60 Fig 5.15……………………………………………………………………………….61 Fig 5.16……………………………………………………………………………….62 Fig 5.17……………………………………………………………………………….63 Fig 5.18……………………………………………………………………………….64 Fig 5.19……………………………………………………………………………….65 | |
| dc.language.iso | en | |
| dc.title | 硫酸吲哚酚對新生大鼠心肌細胞間隙接合的影響 | zh_TW |
| dc.title | Effects of Indoxyl Sulfate on Gap Junction in Neonatal Rat Ventricular Cardiomyocytes | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳建春,鄭瓊娟,陳玉怜 | |
| dc.subject.keyword | 硫酸吲,哚,酚,尿毒素,心肌細胞,細胞間隙接合,細胞間隙接合溝通,蛋白激酶,C,氨基末端激酶, | zh_TW |
| dc.subject.keyword | Indoxyl sulfate,Uremic toxin,Cardiomyocytes,Gap junction,Gap junction intercellular communication,PKC alpha,JNK, | en |
| dc.relation.page | 67 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2011-07-28 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 解剖學暨生物細胞學研究所 | zh_TW |
| 顯示於系所單位： | 解剖學暨細胞生物學科所 | |
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