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系統識別號 U0026-1810201318075900
論文名稱(中文) 內皮細胞對於透析過程血壓的調控角色
論文名稱(英文) Role of endothelial cells in the regulation of blood pressure during hemodialysis
校院名稱 成功大學
系所名稱(中) 臨床醫學研究所
系所名稱(英) Institute of Clinical Medicine
學年度 102
學期 1
出版年 102
研究生(中文) 張懷民
研究生(英文) Huei-Min Chang
電子信箱 s97001132@mail.ncku.edu.tw
學號 s97001132
學位類別 碩士
語文別 英文
論文頁數 126頁
口試委員 指導教授-邱元佑
口試委員-曾進忠
召集委員-林聖翔
中文關鍵字 內皮細胞激素  ㄧ氧化氮  肱動脈血管擴張  脫水量  乾體重 
英文關鍵字 FMD: flow-mediated vessel dilation  endothelin-1  NO: nitric oxide  UF:ultrafiltration volume  Dry weight 
學科別分類
中文摘要 血液透析目前是台灣在末期腎衰竭的主要治療方式, 血液透析每次持續四小時, 這中間可能會產生血壓的不正常變化 ( 低血壓或是高血壓 ) , 不僅會導致病患抽筋、頭痛等不舒服, 甚至透析必須暫時停止, 造成透析不足。長期以後會影響病患日後的預後 , 並造成醫療費用的增加。
內皮細胞所分泌的 endothelin-1是人體內目前已知最強的血管收縮物質 ; 相對而NO ( ㄧ氧化氮) 則是血管舒張物質, 在正常人的血管中, 兩者可以得到很好的調控, 可是如果內皮細胞功能異常 , 大量分泌的endothelin-1會造成血管的異常收縮就有可能導致高血壓或是血管的粥狀硬化 , 造成進一步心血管疾病。
本研究主要探討透析過程中血壓變動時,內皮細胞所扮演的角色, 收集地區透析中心透析血液透析病人61人, 根據最近一個月的透析血壓變動, 分成三組:血壓變動下降≧10mmHg (下降組) ; 血壓變動下降<10mmHg (對照組) 以及血壓上升≧0mmHg (上升組) 三組。同時記錄每位病患於透析前後生化數值及血液檢驗, 經由ELISA kit 分析endothelin-1, NO (nitrate+nitrite) 血清變化, 並分析三組間之變化, 其中發現:透析後的endothelin-1上升在血壓上升這一組呈現顯著性上升 (3.75 ±3.2pg/ml , P=0.0003)。以邏輯迴歸進行危險因子分析則發現:當endothelin-1上升1單位 (pg/ml) 時, 表示透析後的血壓下降>10mmHg的危險度相對於對照組而言是 1.3倍 ( P<0.05) , 另外透析後的血壓上升相對於對照組而言是1.4倍 ( P<0.005)。 這也同時表示血壓上升≧0mmHg及血壓下降≧10mmHg時, 內皮細胞的△endothelin-1會異常上升, 而在肱動脈擴張程度方面 : 當肱動脈擴張每增加1% , 透析後血壓下降危險度相對於對照組而言是0.8倍 (P<0.005) ; 而透析後血壓上升危險度相對於對照組而言 是 0.75倍 (P=0.001) , 這些結果顯示出內皮細胞異常反應者的血壓變動會有顯著性差異。而於多元線性迴歸分析中endothelin-1上升對血壓的變動也呈現顯著線性相關 ( regression coefficient =2.07 , P < 0.005 ) , 且此變化亦與脫水量具有顯著的交互作用( P<0.005 )。
進而我們以立體圖形及ROC curve來整合呈現分析中的整體現象 , 吾人可發現影響透析過程中之血壓變動因素 , 其中內皮細胞之功能扮演了很重要的角色 ; 我們預期可藉由改善內皮細胞功能在未來對透析病人的血壓變化, 將能得到更好的控制。
英文摘要 Blood pressure changes during hemodialysis are very common and make patients uncomfortable by causing muscle cramps or headaches and may affect survival if this change becomes severe to induce hypotension or hypertension for previous studies. However, in regard to the etiology of dialysis, induced hypotension or hypertension remains speculative. This study hypothesizes that this endothelial cell dysfunction may be related to abnormal blood pressure changes after hemodialysis.
In this study, 61 hemodialysis patients in Tainan City, Taiwan were divided into three groups: Control group: hemodynamically stable: BP decrease <10mmHg; Low group : BP decrease ≧10mmHg, and High group: BP increase ≧ 0mmHg. ELISA for serum endothelin-1, NO (nitrite+ nitrate) before and after hemodialysis were also collected from the 61 patients, and statistical analysis was used to determine the differences in the three groups.
Among the three groups, post-dialysis endothelin-1 was higher in both the Low group and High group compared with the Control group (P=0.03). Endothelin-1 changes after hemodialysis was higher in the High group as compared to either the Low group or the Control group. (3.75±3.2 pg/ml, P<0.0005). The odds ratio in polytomas logistic regression in regard to △endothelin-1 for the Low group/Control group was 1.3 (P<0.005), and for the High group/Control group, it was 1.4 (P=0.001). In the multiple linear regression, endothelin-1 changes indicated significance for blood pressure changes after H/D (regression coefficient=2.07, P<0.005) and had strong interactions with UF/Dry BW (%) (P<0.005). A three-dimensional graph was constructed to observe and reflect the changes among the three groups. Therefore we can see that in the case of hemodialysis unstable blood pressure groups, not only did UF play important role in our study, but endothelial function (including FMD or △NO /△endothelin-1) also became important. Maybe in the near future, we can use exercise, diet or even drugs to improve endothelial cell function for these patients in order to make blood pressure more stable during hemodialysis.
論文目次 中文摘要----I
Abstract---III
Acknowledgement-----V
Table of contents---VII
List of tables---IX
List of figures-----XI
Abbreviations----XIII
Experimental materials----XV
Chapter 1 Introduction--1
1.1 Background-1
1.2 Endothelial cell and blood pressure changes in hemodialysis---4
1.3 Our Hypothesis and Study Design-7
Chapter 2 Materials and methods--9
2.1 Patients selection and study procedure---9
2.2 Study for endothelin-1 level11--11
2.3 Study for Nitrate/Nitrite level-12
2.4 Flow-mediated vasodilation testing for the brachial artery---12
2.5 Statistical analysis---13
Chapter 3 Results-16
3.1 Baseline characteristics of 61 study populations--16
3.2 Plasma endothelin-1 before and after hemodialysis-18
3.3 Plasma NO (nitrate+nitrite) level before and after hemodialysis---18
3.4 Plasma NO/endothelin-1 changes before and after hemodialysis and Doppler FMD testing---19
3.5 Correlation for FMD with △NO&△endothelin-1---20
3.6 Risk factors analysis involving BP changes during hemodialysis---20
3.7 △endothelin-1&UF/Dry BW interactions during hemodialysis---21
3.8 Analysis of significant factors using a three- dimensional graphical form and an ROC curve--22
Chapter 4 Discussion-23
4.1 UF with blood pressure changes during hemodialysis24
4.2 Endothelin-1 with blood pressure changes during hemodialysis---25
4.3 NO changes with blood pressure changes during hemodialysis---26
4.4 NO/endothelin-1 changes with blood pressure changes during hemodialysis--27
4.5 FMD with endothelin-1&NO correlation during hemodialysis-28
4.6 Comparison with other papers using different subgroup methods--33
Chapter 5 Conclusions---35
References--37
Table-49
Figure---64
Curriculum vitae--76
Appendix-77
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