| 蛋白分子可能预测肺移植排斥 | | 点击： 作者：51protocol收集 来源： 时间： 2007-06-02 本站论坛 |
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蛋白分子可能预测肺移植排斥
蛋白分子可能预测肺移植排斥
Proteins may predict lung transplant rejection
FORT LAUDERDALE, FL (Nov. 3, 2006) -- Using the latest in high tech tools, researchers have identified three proteins that were highly predictive of chronic lung rejection up to 20 months before the rejection occurred.
蛋白质有可能预测肺的移植排斥反应
劳德代尔堡，FL（2006年11月3日）－－利用新技术，研究人员鉴定出三种蛋白质，它们能够作为移植排斥反应发生前长达20个月的慢性排斥期的高度预测因子。
Lung transplant patients have the highest mortality rate of organ recipients, about 45% over five years, said lead investigator and pulmonologist Chris Wendt. Currently, there is no reliable way to predict which transplants will fail, and when signs of chronic rejection appear, it is usually too late to reverse it, she said. If doctors can predict which patients are beginning to reject the transplanted organ, they could try to head it off, she said.
主研究员，肺病学家Chris Wendt指出：肺移植患者作为器官受体，死亡率很高，五年内死亡率约45%。目前尚无有效方法预测移植手术成败及慢性排斥反应预警信号，最后导致为时已晚，无法逆转，她说。如果医生们能够预测患者何时开始器官排斥，那么它们就会试图解决此问题。
The study, "Proteomic biomarkers of chronic lung allograft rejection," was carried out by Wendt, Tereza Cervenka, Madelaine Haddican, Yan Zhang and Gary Nelsestuen, of the University of Minnesota, Minneapolis. The researchers will present the study during a poster session at the upcoming conference, "Physiological Genomics and Proteomics of Lung Disease," in Fort Lauderdale, Nov. 2-5. The American Physiological Society is presenting the conference.
明尼苏达州立大学的Wendt, Tereza Cervenka, Madelaine Haddican, Yan Zhang，Gary Nelsestuen对“慢性肺同种异体肺移植物的蛋白组学生物性标记”进行研究。于11月2－5日在劳德代尔堡即将召开的“肺病生理基因组学及蛋白组学”研讨会上，这个研究小组将发表他们的研究进展。美国生理学会将出席本次大会。
The researchers used the power of computers and new, sophisticated methods of analysis to find the proteins that form a "biosignature" or "biomarker" of organ rejection from among the thousands of proteins that exist in the lung.
研究人员利用电脑和最新的尖端分析方法在肺组织的数千个蛋白中寻找引起组织排异性蛋白，以此作为组织排异的“生物学信号”或“生物学标记”。
Disease disturbs protein function
疾病扰乱蛋白功能。
Lung transplants are a common therapy for many end-stage lung diseases such as chronic obstructive pulmonary disease, cystic fibrosis, pulmonary hypertension, idiopathic pulmonary fibrosis and other diseases.
肺移植是许多终末期肺病的普遍治疗方法，例如慢性阻塞性肺病、囊性纤维病、肺动脉高血压、特发性肺纤维化等疾病。
Patients who receive a new lung may suffer bouts of acute or chronic rejection. Acute rejection often responds to therapy. Chronic rejection, which results in scarring of the lung's airways following inflammation, is irreversible. In addition, often by the time doctors make the diagnosis, the disease is already fairly advanced, Wendt said.
刚接受肺移植的患者会出现急性或慢性排斥反应。急性排斥是对治疗的应答反应。而导致炎症期后的肺组织瘢痕化的慢性排斥是不可逆转的.Wendt说，通常医生对此做出诊断时，病情已经相当严重了。
"We want to identify people at risk of chronic rejection before they have the clinical manifestations," Wendt said. In addition to early identification, the researchers hope to eventually open the door to developing a preventative treatment and also gain insight into the physiological mechanisms of lung rejection.
“我们想在病人出现临床症状之前确定他们是否处于慢性排斥期，”Wendt说。除了进行早期诊断，研究人员希望最终找到预防性疗法，并深入理解肺排斥的生理性机制。
Lung fluid samples from '93-'96
肺液样本'93-'96
The study used 411 lavage samples obtained from 137 lung transplant recipients from 1993-1996, Wendt explained. A lavage is a liquid that doctors introduce into the lung to wash out unwanted material. When the wash is removed, it contains biological material, including proteins, that the researchers hypothesized would be able to identify those who later suffered organ rejection.
Wendt说，研究使用了93－96年间137名接受肺移植患者的411份肺液样本。灌洗液是医生用来清洗肺中不需要的物质。洗液移出后，可以在其中发现生物活性物质，如蛋白质－－研究者认为是晚期器官排斥的关键因子。
Because this study looked back at patients treated years ago, the researchers could look for differences between patients who subsequently suffered chronic lung rejection and those who did not.
这项研究回顾了数年前接受治疗的患者，研究者能够找到发生慢性肺排斥反应患者同那些不发生慢性排斥反应患者之间的差异。
The researchers combined proteomics (the study of proteins), the latest in mass spectrometry technology and the best analytical methods from the field of bioinformatics (the use of computers and statistics to analyze and find patterns in scads of data). They hypothesized that proteins would change as chronic lung rejection developed and that the new technology would make it possible to find these patterns from among the thousands of proteins at work in the lungs.
研究者将蛋白组学（研究蛋白质），最新的质谱测定技术及最好的生物信息学分析方法（应用电脑及统计学分析并检验大量数据类型）相结合。研究者认为蛋白质会随着慢性肺排斥的进展而发生改变，应用新技术将有可能从肺数以千计的蛋白质中鉴定出发生作用的类型。
Some promising results
一些预期结果
An earlier study from the laboratory had found that elevated levels of human neutrophil peptide (HNP), declining Clara cell secretory protein and some previously unidentified proteins were highly correlated with chronic lung rejection. In particular, the researchers found that HNP was three times more likely to be elevated among those who later suffered chronic rejection.
实验室早期研究发现人类嗜中性肽（HNP)水平升高，细支气管分泌性蛋白质减少及一些尚未鉴定的蛋白质同慢性肺排斥密切相关。特别是，研究者发现HNP在晚期慢性肺排斥患者中升高三倍或更多。
Later analyses identified 265 proteins that were upregulated in lung rejection up to 20 months before it happened. With yet more research, they found the following became elevated with chronic rejection:
后期分析鉴定了肺排斥开始前长达20个月内上调的265种蛋白质。更有研究发现肺排斥中下列因子水平增高：
matrix metalloprotein-9 (66 times more likely to suffer rejection)
proteinase 3 (nine times more likely)
基质金属蛋白酶－9（排斥上升66倍或更多）
蛋白水解酶3（9倍或更多）
"Preliminary evidence suggests these biomarkers will be an early sign of lung transplant rejection," the authors wrote. The research is continuing to determine which protein combinations are the best predictors and whether some biomarkers may be better than others at different points of the disease's development.
“初期实验表明上述生物标记将是肺移植排斥的早期信号，“作者写到。进一步研究哪一种蛋白制品可以作为最佳的预测因子及是否一些生物标记可能在疾病进展不同的时点发挥优势作用。
The information could offer inroads to new therapies, said Wendt. Doctors may be able to increase the dose of anti-rejection drugs when the early markers of rejection appear. Or, they may reduce anti-rejection drugs for people who do not show early signs of rejection. (Anti-rejection drugs have their own side effects, including an increased chance of developing kidney disease or malignancies.)
研究信息能够提供治疗新途径，Wendt说道。医生也许能够在早期排斥出现时增加抗排斥反应的药物剂量。或者，在无早期排斥反应信号出现时减少抗排斥药物用量。（抗排斥药物本身有其副作用，如增加肾疾病或恶性肿瘤的发生几率。）
Finally, these findings could be used to understand the physiological mechanisms that lead to lung rejection, Wendt explained. Her team has developed two mouse models to determine whether these proteins play a role in the development of chronic lung rejection or whether they are a byproduct of the disease.
总之，上述发现有助于理解肺排斥的生理机制，Wendt解释到。她的研究团队已经建立了两只鼠模型来研究是否上述蛋白在慢性肺排斥进展中起作用或仅仅是副产品。
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The American Physiological Society was founded in 1887 to foster basic and applied bioscience. The Bethesda, Maryland-based society has 10,500 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually.
美国生理学会于1887年建立，旨在进行基础及应用生物科学研究。Bethesda，马里兰学会有10,500名成员，14本同行评审类杂志，每年发表约4,000篇文章。
APS provides a wide range of research, educational and career support and programming to further the contributions of physiology to understanding the mechanisms of diseased and healthy states. In 2004, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring.
APS提供一系列研究、教育及行业支持，同时有计划的促进研究，更进一步理解疾病及健康状态下的生理学机制。2004年，APS因在科学，数学及工程管理等方面的突出贡献而受到总统嘉奖。
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