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出血性休克后肠系膜淋巴的蛋白质组学分析。

Proteomic analysis of post-hemorrhagic shock mesenteric lymph.

机构信息

Department of Orthopedics, Chang-Gung Memorial Hospital, Chang-Gung University, Taoyuan, Taiwan.

出版信息

Shock. 2010 Sep;34(3):291-8. doi: 10.1097/SHK.0b013e3181ceef5e.

Abstract

Recent studies have documented the association of mesenteric lymphatic route with adult respiratory distress syndrome and multiple organ failure after hemorrhagic shock. However, the mediators and mechanisms of the toxic effects of mesenteric lymph remain unclear. This study aimed to identify mediators or biomarkers in the mesenteric lymph through comparative proteomic analysis. Fourteen mature male Sprague-Dawley rats were randomly divided and subjected to trauma (laparotomy) plus hemorrhagic shock or trauma plus sham shock. Mesenteric lymph samples were collected before shock and at 3 h after resuscitation from hemorrhagic shock (or sham shock). To investigate changes in proteome profiles between preshock and 3-h postshock (or 3-h post-sham shock) mesenteric lymph samples, two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were performed. We found a more than 2-fold change in abundance of 31 protein spots in the lymph samples. Mass spectrometry analyses identified 12 distinct proteins. Four proteins were consistently upregulated in the 3-h postshock lymph samples, including serum albumin precursor, two isoforms of cytoplasmic actin, complement C3 precursor, and major urinary protein precursor. Two proteins, including haptoglobin and one unidentified protein, were consistently downregulated. The deregulation of these proteins was confirmed by Western blots. Most of these altered proteins are functionally implicated in tissue inflammation. The findings of this study provide a starting point for investigating the functions of these proteins in hemorrhagic shock-induced lung injury and hold great promise for the development of potential therapeutic interventions.

摘要

最近的研究记录了肠系膜淋巴途径与成人呼吸窘迫综合征和出血性休克后多器官衰竭的关联。然而,肠系膜淋巴的毒性作用的介质和机制仍不清楚。本研究旨在通过比较蛋白质组分析来确定肠系膜淋巴中的介质或生物标志物。14 只成熟雄性 Sprague-Dawley 大鼠随机分为创伤(剖腹术)加失血性休克组或创伤加假休克组。肠系膜淋巴样本在休克前和失血性休克复苏后 3 小时(或假休克)采集。为了研究肠系膜淋巴样本在休克前和休克后 3 小时(或假休克后 3 小时)之间的蛋白质组图谱变化,进行了二维凝胶电泳和基质辅助激光解吸电离飞行时间质谱分析。我们发现,在淋巴样本中,有 31 个蛋白质斑点的丰度增加了 2 倍以上。质谱分析鉴定出 12 种不同的蛋白质。在休克后 3 小时的淋巴样本中,有 4 种蛋白质持续上调,包括血清白蛋白前体、两种细胞质肌动蛋白同工型、补体 C3 前体和主要尿蛋白前体。两种蛋白质,包括触珠蛋白和一种未识别的蛋白质,持续下调。Western blot 证实了这些蛋白质的失调。这些改变的蛋白质大多数在功能上与组织炎症有关。本研究的发现为研究这些蛋白质在出血性休克引起的肺损伤中的功能提供了一个起点,并为开发潜在的治疗干预措施提供了很大的希望。

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