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研究生:池惠民
研究生(外文):Chih-Hui Min
論文名稱:第二環氧化酶抑制劑止痛藥對心血管疾病危險因子相關生化指標之研究
論文名稱(外文):Effect of Cox-II inhibitor on biochemical markers in cardiovascular-related adverse effects
指導教授:蔣恩沛
指導教授(外文):En-Pei Chiang
學位類別:碩士
校院名稱:國立中興大學
系所名稱:食品暨應用生物科技學系所
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:107
中文關鍵詞:第二環氧酶抑制劑心血管疾病危險因子臨床生化指標動物模式
外文關鍵詞:COX-2 Inhibitorscardiovascular disease riskbiochemical markeranimal model
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第二環氧酶抑制劑 (Cyclooxygenase II inhibitor, Cox-II inhibitor) 屬於非類固醇類抗發炎藥物的一種,其主要是抑制調控發炎作用和造成疼痛的前列腺素之合成。目前在台灣臨床上使用Cox-II 抑制劑止痛藥之最大族群之一是慢性關節炎病患,主要用於緩解發炎與疼痛。然而在2004年美國一項為期三年的的隨機對照臨床研究中卻發現服用 rofecoxib的患者其產生心血管不良反應的危險性明顯高於對照組,因而造成此藥全球性下市。至於另一被普遍使用之 Cox-II 抑制劑止痛藥 Celebrex是否確實會直接增加心血管副作用的危險性仍未有定論。國內外多項研究顯示Cox-II 抑制劑對不同心血管副作用的相關危險因子所產生之影響有顯著不同。本研究收錄使用及未使用Cox-II 抑制劑Celebrex之病患為臨床研究對象,檢測其血中各脂質代謝相關生化值及心血管病變相關之危險因子。同時也進行動物研究探討正常及高血脂之動物,投予 Celebrex 及非Cox-II抑制劑 Naproxan前後,其血中各脂質代謝相關生化值及心血管病變相關危險因子之變化情形。
動物研究發現餵食正常飲食與高油脂飲食大鼠,血脂無明顯的影響;但投予Celebrex會使血中Hs-CRP濃度下降。臨床觀察發現受測者血中同半胱胺酸濃度與有無使用疾病修飾型抗風濕藥物無明顯相關;服用Celebrex受測者會降低血中三酸甘油脂的濃度;Celebrex合併Prednisolone使用會使受測者血中的HDL濃度增加;Celebrex合併Hydroxychlorquine使用,會降低受測者血中LDL、TC濃度;Celebrex合併MTX及Prednisolone會使受測者血中的HDL濃度增加,但Celebrex隨著疾病修飾型抗風濕藥物種類的多樣性,血脂濃度無顯著上的差異。
第二環氧化酶抑制劑止痛藥對心血管疾病危險因子相關生化指標仍無法綜合判定。
The selective cyclooxygenase-2 (COX-2) inhibitors have been associated with increased cardiovascular risk. The goal of the present study was to investigate the impacts of COX-2 inhibitors on biochemical indices in cardiovascular disease. We studied the effects of Cox-II inhibitor using experimentally induced hyperlipidemic rats. Plasma total cholesterol, LDL and triglyceride concentrations will be determined before and after animals treated with cyclooxygenase-2 (COX-2) inhibitors. Biochemical markers related to cardiovascular events including prostaglandin I2, thromboxaneA2 and others will also be investigated. We also investigated these biochemical markers in patients taking Celebrex and NSAIDs. We hope these studies will reveal clinically useful biochemical markers for cardiovascular events in patients taking Cox-II inhibitor.
Study found that animals fed a normal diet and high fat diet rats, the blood will vote for Celebrex in the Hs-CRP concentrations decreased. Clinical trials found that subjects with serum homocysteine concentration and whether or not the use of Methotrexate, Prednisolone, Sulfasalazin and Hydroxychlorquine on blood homocysteine no significant impact. Subjects taking Celebrex would reduce the concentration of blood triglyceride; Celebrex combined Prednisolone measured by the use of lead in blood to increase HDL concentration; Celebrex combined Hydroxychlorquine use, will be reduced by the measured blood LDL, TC concentrations; Celebrex Prednisolone combined MTX and blood will be tested in the concentration of HDL increased, Celebrex as disease modifying anti-rheumatic drug type of diversity, no significant lipid concentration differences.
We hope these studies will reveal clinically useful biochemical markers for cardiovascular events in patients taking Cox-II inhibitor.
目 次
中文摘要 ----------------------------------------------Ⅰ
英文摘要 ----------------------------------------------Ⅱ
目次 --------------------------------------------------Ⅲ
圖目次 ------------------------------------------------Ⅷ
表目次 ------------------------------------------------Ⅸ
第一章、 研究動機與目的---------------------------------- 1
1.1 研究動機-------------------------------------------- 1
1.2 研究目的---------------------------------------------2
第二章、文獻回顧----------------------------------------- 4
2.1環氧化酶抑制劑止痛藥與心血管的研究------------------- 4
2.2常見的心血管疾病相關危險因子------------------ --------8
2.3 血脂濃度與心血管疾病之關係 --------------------------10
2.4 血中同半胱胺酸濃度的升高為心血管疾病的獨立危險因子---12
第三章、研究內容與方法-----------------------------------15
3.1動物實驗--------------------------------------------- 15
3.1.1血中心血管相關危險因子之測定------------------------16
3.1.2血中脂質代謝相關生化值之測定------------------------17
3.1.3內臟器官重量之測定--------------------------------- 18
3.1.4血漿同半胱胺酸之測定------------------------------- 18
3.1.5血漿磷酸比哆醛之測定------------------------------- 18
3.2 臨床研究-------------------------------------------- 19
3.2.1受測者臨床基本資料收集------------------------------20
3.2.2 藥物服用情形---------------------------------------20
3.2.3 受測者飲食攝取之頻率-------------------------------20
3.2.4 臨床檢體血液生化指標之測定------------------------ 21
3.2.5 血中脂質代謝相關生化值脂測定-----------------------21
3.2.6 反轉錄聚合酶反應之測定-----------------------------21
3.3統計分析----------------------------------------------22
第四章、研究結果-----------------------------------------23
4.1 動物實驗結果-----------------------------------------23
4.1.1 探討血中心血管副作用相關危險因子---------------23 4.1.2 探討內臟器官重量之影響-----------------------------23
4.1.3 探討血中脂質代謝相關生化值之影響------------------ 23
4.1.4 探討同半胱胺酸濃度之影響---------------------------24
4.1.5探討環氧化酶對主動脈弓之影響------------------------24
4.2臨床研究結果------------------------------------------25
4.2.1 受測者人口變數分佈---------------------------------25
4.2.2 藥物劑量與持續時間---------------------------------26
4.2.3環氧化酶抑制劑止痛藥對膽固醇代謝基因之影響----------27
4.2.4 環氧化酶抑制劑止痛藥對血脂之影響-------------------27
4.2.5環氧化酶抑制劑止痛藥對同半胱胺酸與C-反應蛋白之影響28
4.2.6 血中同半胱胺酸單一變量分析-------------------------28
4.2.7 Celebrex 對血中同半胱氨酸多變數分析----------------29
4.2.8 MTX、Prednisolone、Salazopyrin對血中同半胱氨酸濃度
、三酸甘油脂濃度之影響-----------------------------------30
4.2.9環氧化酶抑制劑止痛藥與疾病修飾型抗風濕藥物合併使用對血脂的影響-------------------------------------------------30
4.2.10環氧化酶抑制劑止痛藥對營養素攝取量的影響-----------31
第五章、討論---------------------------------------------32
5.1 環氧化酶抑制劑影響前列腺素I2(6-keto Prostaglandin F1α)、前列凝素A2(Thromboxane B2)及纖維素原(Fibrinogen)之探討---------------------------------------------------- 32
5.2 環氧化酶抑制劑對血中脂質、肝臟中脂質代謝相關生化分析---------------------------------------------------------- 33
5.3 環氧化酶抑制劑止痛藥與血中同半胱胺酸及C反應蛋白指數之探討---------------------------------------------------- 35
5.4 血中維生數B6、血漿葉酸、飲食葉酸之探討--------------37
5.5 類風濕性關節炎發生率分析----------------------------37
5.6 疾病修飾型抗風濕藥物對血中同半胱胺酸之探討----------38
5.7環氧化酶抑制劑止痛藥與疾病修飾型抗風濕藥物合併使用對
血脂的影響-----------------------------------------------38
第六章、結論 -------------------------------------------41
圖 --------------------------------------------------- 44
表 --------------------------------------------------- 49
參考文獻------------------------------------------------ 93
附錄1 名詞縮寫對照表-----------------------------------102
附錄2 成人血中總膽固醇及三酸甘油酯濃度之界定範圍-------103
附錄3 組織病理送檢樣品及編號---------------------------104
附錄4 病理評估標準------------------------------------105
附錄5 大鼠病理評估結果標準-----------------------------106
附錄6 常用環氧化酶抑制劑種類與藥物--------------------107
參考文獻
(一) 參考來源之機關及網址
行政院衛生署食品衛生處食品資訊網:http://food.doh.gov.tw/
世界衛生組織;World Health Organization (WHO):http://www.who.int/en/
美國心臟協會;American Heart Association (AHA):http://www.americanheart.org/presenter.jhtml?identifier=1200000
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