2012-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/659871摘要：前列腺素群是由二十個碳組成的不飽和脂質所衍生出一群具有生物活性的物質。主要分為四大項：前列腺素、環前列腺素、凝血惡烷和白三烯素。在心血管系統中以環前列腺素與凝血惡烷間的作用為主。凝血惡烷會促進血管收縮與血小板活化。環前列腺素則與凝血惡烷有相反的作用。早期研究就指出心肌梗塞後血中凝血惡烷濃度上升，與心肌梗塞區域心肌壞死及白血球的浸潤有關。抑制凝血惡烷的作用能達到降低心臟壞死區域具有保護作用。我們想利用小鼠的心肌梗塞模式來深入研究凝血惡烷與環前列腺素在心肌梗塞時的分子作用。以左前降枝冠狀動脈結紮法建立本急性心肌梗塞模式，以磁振造影分析心臟的各項功能指標變化，然後取正常與梗塞區域的心肌組織中環前列腺素與凝血惡烷受體與合成酶mRNA 與蛋白質表現以獲得心肌梗塞病理變化。並以蛋白質體學分析法與基因晶片分析，希望能發現環前列腺素與凝血惡烷在心肌梗塞時的作用與分子機制。其次、利用凝血惡烷合成酶基因踢除鼠檢驗缺乏凝血惡烷時心臟對缺血與梗塞是否具耐受性，而其他類前列腺素是否有代償性的變化。本實驗結束後可以獲得更多環前列腺素與凝血惡烷在心肌梗塞後的作用機制。期望能在未來對於心肌梗塞病人的治療用藥上可以有另外一個新的思考方向。<br> Abstract: Eicosanoids are lipid mediators with multiple biological function and they arederived from 20-carbon polyunsaturated fatty acid. Prostanoids has beenidentified into four classes; prostaglandins, prostacyclin, thromboxane andleukotrienes. Prostacyclins and thromboxanes are the major eicosanoidsinvolved in cardiovascular system. Thromboxanes enhance vasoconstriction andplatelet activation. Prostacyclins have opposite effects with thromboxans.Thromboxanes are produced abundantly during cardiac ischemia/infarction wereproposed to involve in the thrombosis and leukocyte infiltration (inflammation).Recently other studies have shown that thromboxane synthase inhibitors andthromboxane receptor antagonist have protective effects and reduce myocardialinfarct size in animal studies in vivo. Underlying molecular causes of cardiacdysfunction in myocardium infarction (MI) are still unknown but are expectedto result from causal alternation in gene and protein expression. Therefore,we want to set up an animal model for mouse acute MI to study the molecularmechanisms of the MI, focused on prostacyclin and thromboxae A2. The acutemyocardium infarction animal model will set up by surgical occluding the leftanterior descending coronary artery. Then, characterize of the structural andfunctional changes (left ventricle (LV) end-systolic (ES) volume, LV theend-diastolic volume (EDV), LV stroke volume, cardiac output (CO), and LVejection fraction (EF)) in the myocardium following ischemia- infarction injuryby cardiac magnetic resonance imaging (MRI). Using proteomic investigation (2Dgel electrophoresis) and gene chip assay to examine global alterations inprotein and gene expressions. It should result in generation of new diagnosticand therapeutic molecular markers in the MI pathology. Finally, check themyocardium ischemic resistance when antagonized the thromboxane function andother prostanoid compensatory changes by the thromboxane synthetase knock outmice. In the end of this study, we will give more MI pathophysiologic informationabout prostacyclins and thromboxanes. Hope to open an entirely new directionfor the MI therapy and new drug research in the future.