2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649314摘要：據統計全球每年有數以百萬的人死於創傷，而嚴重創傷會導致三分之一的患者發生出血性休克，併導致高達30-50%患者死亡，大量出血或間接地多重器官衰竭是造成死亡主要的原因。即使能成功存活下來的病患，他們常因嚴重發炎反應導致胃腸道、腎、肝和肺功能的喪失，甚至功能衰竭。在過去幾年，我們的團隊一直熱衷於改進輸液復甦法來治療創傷病患。感謝2005 年、2007 年和2009 年NSC 計劃(94-2314-B-002-138、96-2314-B-002-042MY2、98-2314-B-002-052-MY2)的補助,讓我們發現：限制輸液的復甦策略有更有利於病患的急救;最佳輸液復甦的血壓；升壓劑(vasopressors)與輸液復甦一起使用的好處;以及在心肺復甦術急救時使用超音波檢查的好處。這些努力讓我們在近五年發表了11 篇關於創傷和33 篇關於急診醫學的論文，也建立了創傷研究的基礎。骨髓含有幹細胞和前驅細胞(progenitorcells)可以幫助各種缺血和發炎的組織愈合。一些臨床研究發現在急性心肌梗塞(AMI)和急性血管損傷後後,骨髓會釋放這些內皮前驅細胞（EPCs）在周邊血液中，研究中還發現內皮前驅細胞的增加能夠改善左心室收縮功能。出血性休克與急性心肌梗塞的病患有很多共同特性，兩者都是由於缺乏含氧血造成器官持續的損傷。因此，我們認為急性心肌梗塞幹細胞相關的研究也可以應用在缺血性休克上。據文獻報導已經有一個實驗室成功的使用骨髓來源的幹細胞減輕大鼠失血性休克的內臟器官損傷。雖然直接用骨髓裏的幹細胞研究失血性休克是可行的，但我們還不知道多少幹細胞會在失血性休克的時候會被骨髓釋放到周邊血液裏。因此，我們的首要目標是在創傷出血性休克的動物模型分離並鑑別出循環幹細胞。我們將用一個新的白血球去除系統叫PowerMag。PowerMag 是一個裝了anti-CD45 磁選柱(magneticseparationcolumn),可以吸掉白血球又同時不讓液體的容量增加。這個去蕪存菁的方法已被驗證可以在1CC 的血液裏分離出少量的循環腫瘤細胞。所以我們相信該技術可以配合immunofluorescence 來分離並鑑別出同樣罕見的循環幹細胞。次要目標是在失血性休克的創傷病患分離並鑑定出周邊循環幹細胞。第一年的動物實驗我們將分離並鑑別循環幹細胞，以協助我們在第二年更有效率的從病患分離出循環幹細胞。第三年，我們將探討使用體循環幹細胞作為出血性休克的預測性生物指標(prognosticBiomarker)的可行性。我們將用損傷嚴重程度評估（TraumaandInjurySeverityScore,TRISS）創傷病患再跟循環幹細胞的數目做比較存活分析。TRISS 是利用患者的年齡，損傷類型，修訂創傷評分（RevisedTraumaScore）和外傷嚴重度評分（InjurySeverityScore），來估計生存的概率。目前我們已發表了3篇生物指標相關的文獻，有很多統計和醫療經驗可以協助完成這個研究並達成目標。<br> Abstract: Millions of people died from traumatic injuries every year. It has been estimated that aboutone-third of those with severe traumatic injuries suffer from trauma-associated hemorrhagic shock(HS). Mortality can result directly from the massive blood loss or indirectly due to multiple organfailure.In the last decade, our group has been interested to make improvement to the standard fluidresuscitation therapy for trauma-associated HS. Using our 2005, 2007 and 2009 NSC project(94-2314-B-002-138, 96-2314-B-002-042MY2, 98-2314-B-002-052-MY2), our group has betterdefined the method for resuscitation by finding out: restricted fluid resuscitation strategy has morefavorable patient outcome; the target blood pressure for resuscitation; the benefit of usingvasopressors together with fluid resuscitation; and the benefit of using ultrasonography incardiopulmonary resuscitation. All together, 11 SCI manuscripts related to HS, and 33 SCImanuscripts related to emergency medicine have been published in the last 5 years.The bone marrow contains stem and progenitor cells capable of generating neovessels in responseto ischemia and inflammation. Clinical studies have shown these endothelial progenitor cells canbe released into the peripheral blood shortly after acute myocardial infarction (AMI) and acutevascular insult. In AMI, the increased percentage of endothelial progenitor cells (EPCs) have evenbeen found to correlate with improved LV systolic function. Patients undergoing HS share manycommon properties to patients with AMI. In which, both patient sustain damages to organs due tolack of oxygenated blood. Thus, we believe that many of the stem cell related advances in acutemyocardial infarction (AMI) could be applied in HS. In fact, one animal study has successfully usebone marrow derived stem cells to attenuate the organ injury associated with hemorrhagic shock.However, it is still unclear when and how many stem cells can be released into the peripheral bloodduring HS. In year one, we will isolate and enumerate circulating stem cells in animals undergoingtrauma-associated HS. A new leukocyte depletion technique called PowerMag system that has beenused to identify as few as 3 circulating tumor cells, will be used to enrich the stem cell population.The PowerMag system is a magnetic column packed with anti-CD45 antibody. This column can beused to remove mature white blood cells with little volume dilution. The filtrate of the PowerMagsystem can then be stained for stem cell specific antibody.In the second year, the aim is to isolate and enumerate different types of circulating stem cells inhuman patients with trauma-associated HS. We will be using results from our animal modelexperiment to help us accomplish our second aim. Finally, in the third year, the possibility of usingcirculating stem cells as a prognostic biomarker for HS patients will be investigated. Patients willbe classified using the Trauma and Injury Severity Score (TRISS), and the number of circulatingstem cells will be compared. TRISS utilizes the patient’s age, type of injury, Revised Trauma Scoreand the Injury Severity Score to estimate the probability of survival. We have the statistical andmedical experience for this aim and have published 3 recent papers on prognostic biomarkerresearch.幹細胞再生細胞創傷損傷出血性休克預測性生物指標Stem cellsregenerative cellstraumainjuryhemorrhagic shock and prognostic biomarker