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研究生:戴任恭
研究生(外文):Zen-Kong Dai
論文名稱:肺動脈血流及壓力增加對肺臟內皮性一氧化氮生成酶與內皮素基因表現之研究
論文名稱(外文):The effects of increased pulmonary arterial flow and pressure on the gene expression of endothelial nitric oxide synthase and endothelin-1 in lungs
指導教授:吳俊仁
指導教授(外文):Jiunn-Ren Wu
學位類別:博士
校院名稱:高雄醫學大學
系所名稱:醫學研究所博士班
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:112
中文關鍵詞:一氧化氮生成脢內皮素-1前內皮素-1心衰竭反轉聚合酶連鎖反應放射免疫分析法免疫組織化學染色法西方點墨分析法主動脈縮窄主動脈下腔靜脈分流肺血管再模化高血壓一氧化氮變形應力先天性心臟病肺血流左至右分流
外文關鍵詞:Reverse transcriptase Polymerase Chain ReactionHeart failureEndothelial Nitric Oxide Synthase (eNOS)Endothelin-1Prepro ET-1Pulmonary flowNitric Oxide (NO)Shear stressCongenital heart diseaseAortic bandingLeft to right shuntAortocaval shuntPulmonary vascular remodelingPulmonary hypertension(RT-PCR)Western blottingRadioimmonoassay (RIA)Immunohistochemical staining
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當肺動脈血流或壓力增加,可見肺血管再模化現象,最後演變為肺高血壓,其嚴重度與可逆性與否,已成為治療先天性心臟病之重要指標。其中一氧化氮生成脢(eNOS)及內皮素(ET-1)分別是影響血管張力的主要介質。在缺氧或monocrotaline肺高血壓實驗,常見兩者基因表現有所改變;但是,模擬先天性心臟病,探究肺血管血行動力學與兩者基因表現改變之研究,則相當少見。本研究即分別以兩種模型:一、藉主動脈上腔靜脈分流術,來增加肺動脈血流。二、藉升主動脈縮綁術,造成因心衰竭的逆行性肺高血壓。經不同時間,先審視肺臟再模化現象,再研究兩者基因表現之改變及其分佈位置。結果顯示:肺血流增加,並未見肺動脈血壓及全身壓力改變。4週後可見血管再模化,在8週後可見eNOS的mRNA及蛋白質表現上升、肺微小動脈的內皮細胞層亦有較多分佈; ET-1則僅於12週後有mRNA亢進。經主動脈縮綁,造成肺高血壓及全身動脈壓力下降,可見eNOS與ET-1在mRNA及蛋白質表現均有上升,且在肺微小動脈的內皮層含量增加。總之,因肺血流動增加所造成之再模化肺臟,未形成肺高血壓以前,eNOS與ET-1的 mRNA亢進會有時間先後,但其ET-1蛋白質並未上升。因心衰竭所致之肺高血壓,亢進的ET-1及eNOS基因表現,與缺氧性肺高血壓相似。
While the pulmonary flow or pulmonary arterial pressure increases, the pulmonary vascular remodeling and altered pulmonary vascular reactivity will be noted, subsequently pulmonary hypertension develops. On the strategy for treating the children with congenital heart disease, it is crucial to evaluate the severity or irreversibility of the pulmonary hypertension. Accordingly, endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1), the major vasomediators in the lung, of which gene expression are frequently altered in hypoxia or monocrotalin induced pulmonary hypertension models. But there were few models mimicking congenital heart diseases. In the study, there were two Wistar models created: An abdominal aortocaval shunt for increasing pulmonary flow, and an ascending aortic banding for heart failure accompanied with pulmonary hypertension. The pulmonary gene expression of both by Western blotting, competitive RT-PCR, RIA and immuno- histological staining were studied. Results: 1) There was no change in pulmonary arterial pressure at 4 wks, 8 wks and 12 wks after aortocaval shunt. The medial hypertrophy of pulmonary arterioles began at 4 wks after shunt. The eNOS gene expression was up-regulated at 8 wks after shunt, and 4 wks prior to that of ET-1, at the transcriptional level. At 12 wks, the ET-1 mRNA increased while the ET-1 protein was not altered. 2) At 12 wks after aortic banding, the pulmonary arterial pressure significantly increased, and increased eNOS and ET-1 gene expression were noted. In conclusion, a chronic increased pulmonary flow could up-regulate eNOS expression followed by an increased expression of preproET-1 mRNA before the development of PH. And, the increased gene expression eNOS and ET-1 in the mediation of pulmonary hypertension in aortic banding, similar to the hypoxia-induced pulmonary hypertension
目 錄
中文摘要……………………………………………………..1
關鍵詞………………………………………………………..2
英文摘要……………………………………………………..3
第一章 緒論………………………….……………………...5

第二章 肺血流增加所造成肺臟內皮性一氧化氮
生成酶與內皮素基因表現改變
前 言…………………………………………….…..13
材料與方法………………………………………….15
結果………………………………………………….22
圖 表………………………………………………...24
討論………………………………………………….29
第三章 慢性肺血流增加,在不同時期造成
肺臟內皮素-1及內皮性一氧化氮生成
酶基因表現變化之研究
前 言………………………………………………..33
材料與方法…………………………………………34
結 果………………………………………………..39
圖 表………………………………………………..42
討 論…………………………………………………49
第四章 心臟衰竭導致肺高血壓,其對肺臟內皮性
一氧化氮生成酶與內皮素基因表現之
影響作用
前 言…………………………………………………53
材料與方法…………………………………………..54
結 果…………………………………………………58
圖 表……………………………………………….…61
討 論………………………………………………….69
第五章 總 結……………………………….………..73
圖 表………………………………………….……….79
參考文獻……………………………………………………..81
已發表論文目錄……………………………………………95
參考文獻

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