臺灣博碩士論文加值系統

眾所周知，這項運動有益於健康，降低患心血管疾病和糖尿病的風險。此外，運動可使心肌梗塞患者的心臟病死亡率降低26％。肌動蛋白是生物體中重要的細胞因子，其主要在運動後從肌肉細胞分泌。其功能可促進血管生成，修復和再生組織，維持身體的正常功能，影響免疫調節，並涉及許多全身性疾病的慢性炎症。 2012年，Boströmet發現了一種名為FNDC5的肌肉細胞因子，他們聲稱FNDC5表達引發一系列事件，裂解為最終產物為Irisin，導致白脂肪“褐變”。然而，由於當時ELISA試劑對於檢測Irisin專一性不高，因此該發現被懷疑其真實性。這疑問最終被Spiegelma的串聯質譜法驗證。此後，關於Irisin的大量論文在世界範圍內發表，其中一個研究機構被發現其對血管生成的影響及其對糖尿病和心血管疾病的可能有益作用。Fei Wu等的結果表明它可以誘導人臍靜脈內皮細胞的細胞增殖，遷移和管形成。在Tg（fli-1：EGFP）y1斑馬魚試驗中，它對血管生成具有顯著影響。然而，目前對於血管內皮生長因子（VEGF）和（缺氧誘導因子1α）HIF-1α參與Irisin功能過程的研究較少。此外，Irisin在糖尿病傷口癒合中應用的效果或減輕心肌損傷的途徑仍然不確定。因此，我們使用從大腸桿菌中表達和純化的重組FNDC5 / Irisin來驗證它們在大鼠糖尿病傷口癒合和心肌缺血性灌注模型中的功能，並闡明了我們的新發現。

It is well known that exercise is good for health and reduces the risk of cardiovascular disease and diabetes. In addition, exercise can reduce cardiac mortality by 26% among people who have experienced myocardial infarction. Myokines are important cytokines in organisms and are a major secretion from muscle cells after exercise. They can promote angiogenesis, repair and regenerate tissue, preserve normal functions of the body, affect immune modulation, and are involved in chronic inflammation in many systemic diseases. In 2012, Boström et al. found a new myokine called FNDC5, and they claimed that its expression in muscle triggers a sequence of events that lead to its trans-membrane cleavage with a final product of irisin, which causes the “browning” of fat. However, this finding has been doubted because the commercial ELISA kits used were not specified for the detection of irisin. The evidence was finally verified using tandem mass spectrometry by Spiegelman. Since then, numerous papers regarding irisin have been published worldwide, and some have found that it has an effect on angiogenesis is possibly beneficial for diabetes and cardiovascular diseases. Wu et al. showed that it can induce cell proliferation, migration, and tube formation in human umbilical vein endothelial cells. In a Tg (fli-1:EGFP)y1 zebrafish assay, it had a significant effect on angiogenesis. However, there is little study on whether vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1α (HIF-1α) are involved in the functional process of irisin. Moreover, it remains uncertain what the effects of irisin are in diabetic wound healing or the pathway to attenuate the myocardial injury. Therefore, we used recombinant FNDC5/irisin expressed and purified from E. coli to determine its function in a model of diabetic wound healing and ischemic perfusion model using rats.

論文審定書 i
摘要 ii
Abstract iv
Chapter 1. FNDC5 therapy for diabetic wound healing 1
1.1 Introduction 2
1.2 Material and methods 4
1.3 Results 7
1.4 Discussion 9
1.5 Figures and legends 12
Chapter 2. The role of irisin in proangiogenic pathways including VEGF and nitric oxide signaling in endothelial cells 16
2.1 Introduction 17
2.2 Materials and methods 20
2.3 Results 29
2.4 Discussion 34
2. 5 Figures and legends 38
Chapter 3. The role of irisin in myocardial protection 53
3.1 Introduction 54
3.2 Materials and methods 56
3.3 Results 58
3.4 Discussion 63
3. 5 Figures and legends 65
Conclusion 74
References 77
Appendix 85

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