在臨床上，急性冠心症(acute coronary syndrome)包括急性心肌梗塞(acute myocardial infarction)常會導致心臟收縮功能異常(systolic dysfunction)、心肌纖維化(cardiac fibrosis)及心臟衰竭(heart failure)。如何減緩急性心肌病變產生的心臟受損，是治療這類患者的重要議題。處理急性心肌病變(acute cardiomyopathy)例如急性冠心症，雖然已經有實證為基礎的指引所建議的療法，尋找更有效的藥物治療來改善心肌受損，仍然相當重要。在此論文中，我探討治療末期腎衰竭病患的維他命D活化藥物paricalcitol治療isoproterenol (ISO) (一種乙型腎上腺素受體促進劑與心臟毒劑)所誘發急性心肌病變大鼠，目前paricalcitol對急性心肌病變的作用及機轉仍未清楚。研究結果發現paricalcitol能減緩ISO所誘發急性心肌病變，改善心肌功能，減少心肌纖維化。同時更發現急性心肌病變過程中心肌內皮細胞標記會轉變為中胚纖維細胞標記的表現，細胞同時表現出兩種細胞標記。由研究結果推論paricalcitol減低ISO所誘發心肌纖維化，可能牽涉調控內皮細胞轉變為纖維母細胞表現的修復機制。期望藉此發現提供臨床上研究或治療的參考。

In clinical practice, acute coronary syndrome containing acute myocardial infarction (AMI) often leads to systolic dysfunction, cardiac fibrosis and heart failure. How to minimize acute cardiac damage is a critical issue for treating patients with AMI. Although guidelines recommend evidence-based treatments for managing patient with acute cardiomyopathy, it remains really crucial to seek effective drugs to minimize acute cardiac damage and improve outcome. In the thesis, I investigated the effect and mechanism of paricalcitol, a vitamin D activator, on cardiomyopathic rats. Paricalcitol has been utilized for treating patients with advanced renal disease. However, the effect of paricalcitol in cardiomyopathic rats induced by isoproterenol (ISO, a beta adrenergic receptor agonist and a cardiotoxin) remain unclear. The results observed in the study showed that paricalcitol attenuated the severity of ISO-induced cardiac dysfunction and fibrosis. The study also found that endothelial-to-mesenchymal cell transition (EndoMT) occurred during the period of developing acute cardiomyopathy with colocalization of two different cell markers. The findings infer that the decrease in ISO-induced cardiac fibrosis by paricalcitol injections may be partially attributed to regulation of EndoMT by paricalcitol injections. We hope these findings will be helpful to further clinical researches and treatments.

國立中山大學研究生學位論文審定書 i
致謝 ii
摘要 iv
ABSTRACT v
INDEX v
FIGURES INDEX ix
TABLE INDEX xi
ABBREVIATIONS AND ACRONYMS xii
CHAPTER 1 1
Introduction 1
1.1 Acute Coronary Syndrome (ACS) 2
1.2 Inflammation Triggered in Acute Cardiomyopathy 4
1.3 ISO Induced Acute Cardiomyopathy 5
1.4 A Vitamin D Activator Paricalcitol 6
1.5 Endothelial-to-Mesenchymal Cell Transition (EndoMT) on Acute Cardiomyopathy 7
1.6 Hypothesis and Specific Aims 9
1.7 Experimental Design 10
CHAPTER 2 11
ISO induced acute cardiomyopathy 11
2.1 Background 12
2.2 Specific Aims 13
2.3 Materials and Methods 14
2.4 Results 18
2.5 Discussion 21
2.6 Figures and Legends 22
2.7 Table 26
CHAPTER 3 28
Effects of paricalcitol in ISO-treated rats 28
3.1 Background 29
3.2 Specific Aims 32
3.3 Materials and Methods 33
3.4 Results 36
3.5 Discussion 38
3.6 Figures and Legends 40
CHAPTER 4 46
Effects of paricalcitol on EndoMT in the ISO-treated rats 46
4.1 Background 47
4.2 Specific Aims 48
4.3 Materials and Methods 49
4.4 Results 52
4.5 Discussion 53
4.6 Figures and Legends 55
CHAPTER 5 59
Conclusions 59
Limitations and Future Perspectives 61
REFERENCES 65
PUBLICATIONS 81
CONFERENCE PRESENTATIONS 85

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