國立臺灣大學醫學院外科許榮彬2006-07-262018-07-112006-07-262018-07-112003-07-31http://ntur.lib.ntu.edu.tw//handle/246246/24490心臟衰竭的原因，或是因為心臟本身功能不足，或是由於其他身體組織需求過高。前者 之主因有冠狀動脈疾病、心臟瓣膜疾病、高血壓，後者則主要肇因於不明原因的心肌病 變。心臟衰竭病人的治療費用，佔整個醫療資源的比例，有逐漸增加的趨勢。不當的治 療，勢將導致死亡率與致病率的上升，形成社會沉重的負擔。 然而心臟衰竭的基本生理學，至今仍不甚瞭解。經由分生實驗顯示，似乎有各種機轉參 與其中。近來更有實驗顯示，心肌內細胞骨骼之變化，可能與心臟衰竭病程之演變有關。 以往，確有許多實驗研究細胞之骨骼蛋白修飾基之變化，並試圖了解這些修飾基與骨骼 蛋白系統功能的關聯。然而，這些實驗使用的材料範圍甚廣，包括許多不同的細胞與組 織，至於心肌內細胞骨骼蛋白修飾基的研究，目前仍未有任何有系統的探討。本計劃運 用動物實驗之模式，以創新之蛋白質分析技術來探究心臟衰竭的病程當中、心肌細胞內 細胞骨骼蛋白結構之變化。我們在二維電泳的實驗中發現，某些心肌蛋白質的表現會增 加，而某些會受到抑制。而受到抑制的蛋白質中，有兩個是蛋白酶的抑制蛋白，似乎意 味著蛋白酶的活性增加與心肌衰竭的發生有關。而這些初步的成果也證明我們的實驗系 統已完備，可以用來研究細胞骨骼蛋白的結構性變化。Heart failure is defined as the pathologic state of impaired cardiac function rendering the heart unable to maintain an output sufficient for the metabolic requirements of the body’s tissues and organs. Heart failure refractory to medical treatment consumes an ever increasing amount of health care resources. Heart failure is a major public health issue. It is a major source of morbidity and mortality, is expensive to treat and is frequently treated inappropriately. Although progress has been made in our understanding of the basic pathophysiology of heart failure, many mechanisms involved remain unclear. Applications of the techniques of molecular and cell biology to the study of heart failure are providing new insights into the mechanisms responsible for this important clinical problems. The basic mechanisms involved include beta-adrenergic recepters, cytokines, nitric oxide, and apotosis. There is some evidence indicating that cytoskeletal proteins like tubulin and desmin are also crucial for development of pathologic processed leading to heart failure. Here, using an animal model of LV pressure overload, we would like to investigate the in vivo structural changes of cytoskeletal proteins during the evolution to heart failure. The two-dimensional gel electrophoresis revealed that a small group of proteins are differentially expressed between normal rats and those with one-month cardiac pressure overload. Thus far, we found that the expression of two proteinase inhibitors was severely reduced. It should be intriguing to explore whether enhanced proteinase activity might be involved in functional changes related to heart failure. Nevertheless, these preliminary data showed that this model system should be of great use in the studies about the cytoskeletal changes during the disease process.application/pdf151510 bytesapplication/pdfzh-TW國立臺灣大學醫學院外科細胞骨骼心肌衰竭蛋白質修飾基液相層析-串聯式質譜儀術cytoskeletonheart failurepost-translational modificationLC/MS/MS[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/24490/1/912314B002225.pdf