DC 欄位 | 值 | 語言 |
dc.contributor | 吳寬墩 | zh-TW |
dc.contributor | Wu, Kwan-Dun | en |
dc.contributor | 臺灣大學:臨床醫學研究所 | zh-TW |
dc.contributor.author | 楊豐榮 | zh-TW |
dc.contributor.author | Yang, Feng-Jung | en |
dc.creator | 楊豐榮 | zh-TW |
dc.creator | Yang, Feng-Jung | en |
dc.date | 2008 | en |
dc.date.accessioned | 2010-05-10T09:57:51Z | - |
dc.date.accessioned | 2018-07-06T07:15:52Z | - |
dc.date.available | 2010-05-10T09:57:51Z | - |
dc.date.available | 2018-07-06T07:15:52Z | - |
dc.date.issued | 2008 | - |
dc.identifier.other | U0001-2807200802371100 | en |
dc.identifier.uri | http://ntur.lib.ntu.edu.tw//handle/246246/181639 | - |
dc.description.abstract | A. 背景臨床上觀察,腎臟對體液的調節可以改變電解質以及代謝物的排泄。譬如,體液減少時,腎臟對於尿酸的排泄減少,導致血中尿酸升高;此外,體液減少時也會發生高血鈣症,其主要原因也是腎臟對鈣離子的排泄減少。相反的,體液擴張的時候,尿酸和鈣離子的排泄都增加。 這些現象的機轉過去研究很多,通常是以生理的技術和觀點解釋,但在分子層次的研究則很少。以尿酸為例,其在腎小管的再吸收(reabsorption),其中牽涉和陰離子的主動交換體(active anion excahnger),而其所需的運轉能量則是靠著鈉離子落差(Na gradient)產生的力量。排尿酸藥物(uricosuric agent)可以阻斷這樣的交換體作用。液的變化會影響腎素–血管張力素系統,使全身性和腎臟局部的血管張力素II(angiotensin II, AII)增加。AII增加可以增加近端腎小管的鈉離子再吸收,近年來發現,阻斷第一型血管張力素受體(angiotensin type I receptor, AT1R)的藥物(AT1R blockade, ARB),特別是losartan,可以降低尿酸。這類藥物是如何降低尿酸的再吸收,仍不完全清楚。近年,有關尿酸運轉的分子被發現,稱之為第一型尿酸運轉體(URAT1),這個分子如何被調控仍不很清楚。液減少影響的鈣離子的排泄,主要發生在近端和遠端腎小管,但是維生素D(vitamin D)的作用在過去的研究顯示,只有在遠端腎小管。然而,研究顯示vitamin D受體(vitamin D receptor, VDR)除了遠端腎小管外,也分布在近端腎小管;果如此,此分布在近端腎小管的VDR是否參與鈣離子的排泄,其調控是否受到AII的影響,是值得研究的主題。研究吾人擬在細胞培養層次上,探討AII是否可能經由 AT1R,調節URAT1和VDR的表現,以此作為探討尿酸和鈣離子在近端腎小管的運送機轉模式。. 研究設計與方法臟中VDR和URAT-1大多存在近端小管細胞中。以近端小管細胞為主軸,以Angiotensin II作剌激,測定URAT-1/VDR的mRNA and protein 所可能產生的變化。再以Ang II 的拮抗劑,來看是否可以拮抗Ang II所帶來的效果。. 結果ng II 會增加VDR/URAT-1的表現, Valsartan可部份壓抑VDR/URAT-1 mRNA 及Protein的量的趨勢,PD123319可部份增加VDR/URAT-1 mRNA 及Protein的量的趨勢。. 討論ng II 可能經由 AT-1的受器,進而調節VDR/URAT-1的反應,可以部份解釋對AT1受器拮抗劑產生預防心血管的效果及產生降尿酸的效果,提供可能的機轉。 | zh-TW |
dc.description.abstract | Background: olume status is linked with the function of our kidney. The body volume decreased with increasing serum uric acid level and serum calcium level due to decreasing the clearance of both. Angiotensin II increased proximal tubule sodium reabsorption. Losartan, a kind of angiotensin type I receptor, AT1R blocker has hypouricemia effect. vitamin D receptor has the effect on the renal distal tubule of calcium metabolism. Reports relating hyperuricemia and hypertension have been filed for many decades. Nevertheless, controversy remains concerning serum uric acid concentration as an independent risk factor underlying coronary heart disease (CHD) and essential hypertension or as an indirect marker of renovascular involvement.Recent studies showed VDR and uric acid are prognostic factors in chronic kidney disease. Renal renin-angiotensin system may play a role in hyperuricemia and cardiovascular negative factor. his study is designed to clarify the interaction among Ang II, Vitamin D receptor, uric acid transporter. The immortalized human kidney (HK-2) cell line used during this work is of proximal tubule origin and was originally isolated from a normal human kidney.ethods: uman proximal tubular cells were cultured in hormonally defined medium. Cells at 80% confluency were exposed to Angiotensin II for 1-24 hours. Activity and expression of URAT-1 was examined by PCR and Western blot analysis. Activity and expression of VDR was examined by PCR and Western blot analysis also.esults:ngiotensin II resulted in a dose-dependent increase in the expression of VDR/URAT-1. AT1 antagonist provided the suppression but showed without significant suppression of Ang II effect. AT2 antagonist provided the augmentation but showed without significant ehancement of Ang II effectonclusion: he effects of rennin-angiotension system on proximal tubular URAT-1/VDR expression are mediated through the pathway of Angiotensin II. Angiotensin II can up-regulate the URAT-1/VDR and be suppressed with Angiotension II receptor type I blocker. To These findings may provide new insights into the role of RAS system in the development and possible therapeutic intervention in hyperuricemia and CKD. | en |
dc.description.tableofcontents | 序言 7文摘要 9. 背景 9. 研究設計與方法 9. 結果 10. 討論 10文摘要 11I. 縮寫表 13II. 圖目錄 15. 實驗藥物示意圖 15一1 Angiotensin II 15一-2 Valsartan 16一-3 PD123319 17. 本實驗所採用的cDNA序列(標底線為primer辨識處) 18二-1 Uric acid transportor transcript variant 1序列 18二-2 Uric acid transportor transcript variant 2序列 21二-3 VDR transcript variant 1序列 23二-4 VDR transcript variant 2序列 27三Concentrations and sources of proximal tubule and interstitial angiotensinogen, angiotensin I and angiotensin II levels 31四 Immunocytochemistry確定URAT-1存在於本細胞中(A/B) 32五Ang II 對URAT-1 Protein的影響 33六AT1/AT2 拮抗劑對URAT-1的影響 34七Ang II 對VDR mRNA的影響 36八Ang II 對VDR protein的影響-劑量與時間的效應 37九AT1/AT2 拮抗劑對VDR的影響 38V. 表目錄 39一人體尿酸的衡定 39二Four compartment theory 40三Proposed membrane topology model of the urate/anion exchanger URAT1 (SLC22A12) 41四Urate transport in the human renal proximal tubule 42五AT1拮抗劑的比較 43六維生素D的身體中的代謝路徑及維生素D在腎臟中的角色 44七維生素D受器(VDR)存在的組織 45八VDR活化產生調控的蛋白質 46. 論文正文 47. 研究背景 47. 維生素D和renin-angiotensin system的關係 48. 尿酸的角色和renin-angiotensin system的關係 48. 實驗假說 50. 實驗目的 51. 研究方法與材料 51. 實驗材料 51. 細胞培養 54. Immunocytochemistry確定URAT-1的存在 55. Angiotensin II對HK2 細胞的URAT-1和VDR影響-劑量與時間的效應 55. AT1與AT2拮抗劑對URAT-1和VDR調控的影響 56. 以反轉錄聚合酵素連鎖反應(RT-PCR)測定URAT-1 mRNA的表現 56. 以西方墨點法(Western blot)測定URAT-1蛋白質表現 57. 統計方法 58. 結果 59. 細胞培養和基本的技術的培養: 59. Immunocytochemistry確定URAT-1存在於本細胞中。 59. Ang II 對URAT-1 mRNA/Protein的影響-劑量與時間的效應 59. Ang II 對 VDR mRNA/Protein的影響-劑量與時間的效應 60. AT1拮抗劑(Valsartan)對URAT-1 mRNA/Protein的影響 60. AT2拮抗劑(PD123319)對URAT-1 mRNA/Protein的影響 60. AT1拮抗劑(Valsartan)和AT2拮抗劑(PD123319)對URAT-1 mRNA/Protein的影響 60. AT1拮抗劑(Valsartan)對VDR mRNA/Protein的影響 61. AT2拮抗劑(PD123319)對VDR mRNA/Protein的影響 610. AT1拮抗劑(Valsartan)和AT2拮抗劑(PD123319)對VDR Mrna/ Protein的影響--------------------------------------------------------------------61. 討論及展望 62I. 參考文獻 66目錄. 實驗藥物示意圖 15一1 Angiotensin II 15一-2 Valsartan 16一-3 PD123319 17. 本實驗所採用的cDNA序列(標底線為primer辨識處) 18二-1 Uric acid transportor transcript variant 1序列 18二-2 Uric acid transportor transcript variant 2序列 21二-3 VDR transcript variant 1序列 23二-4 VDR transcript variant 2序列 27三Concentrations and sources of proximal tubule and interstitial angiotensinogen, angiotensin I and angiotensin II levels 31四 Immunocytochemistry確定URAT-1存在於本細胞中(A/B) 32五Ang II 對URAT-1 Protein的影響 33六AT1/AT2 拮抗劑對URAT-1的影響 34七Ang II 對VDR mRNA的影響 36八Ang II 對VDR protein的影響-劑量與時間的效應 37九AT1/AT2 拮抗劑對VDR的影響 38目錄一人體尿酸的衡定 39二:Four compartment theory 40三Proposed membrane topology model of the urate/anion exchanger URAT1 (SLC22A12) 41四Urate transport in the human renal proximal tubule 42五AT1拮抗劑的比較 43六維生素D的身體中的代謝路徑及維生素D在腎臟中的角色 44七維生素D受器(VDR)存在的組織 45八VDR活化產生調控的蛋白質 46 | en |
dc.format | application/pdf | en |
dc.format.extent | 1881710 bytes | - |
dc.format.mimetype | application/pdf | - |
dc.language | zh-TW | en |
dc.language.iso | en_US | - |
dc.subject | 維生素 D受器 | zh-TW |
dc.subject | 尿酸 | zh-TW |
dc.subject | 第二型血管加壓素 | zh-TW |
dc.subject | 近端小管細胞 | zh-TW |
dc.subject | URAT-1 | en |
dc.subject | uric acid | en |
dc.subject | Vit D | en |
dc.subject | Vit D receptor | en |
dc.subject | CKD | en |
dc.subject | Angiotensin II | en |
dc.subject | renal proximal tubule cel | en |
dc.subject.classification | [SDGs]SDG3 | - |
dc.title | 腎臟近端腎小管中維生素D、尿酸代謝與第二型血管加壓素之關係探討 | zh-TW |
dc.title | The relationship between Vitamin D, Urate metabolism and Angiotensin II in renal proximal tubule | en |
dc.identifier.uri.fulltext | http://ntur.lib.ntu.edu.tw/bitstream/246246/181639/1/ntu-97-P93421009-1.pdf | - |
item.fulltext | with fulltext | - |
item.languageiso639-1 | en_US | - |
item.grantfulltext | open | - |
顯示於: | 臨床醫學研究所
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