Department of Medicine/Gastroenterology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Neurogastroenterol Motil. 2011 Apr;23(4):379-86, e164. doi: 10.1111/j.1365-2982.2011.01675.x. Epub 2011 Feb 9.
Trauma is a leading cause of death and although the gut is recognized as the 'motor' of post-traumatic systemic inflammatory response syndrome and multiple organ failure, studies on the gastrointestinal (GI) tract are few. Our objectives were to create a precisely controllable tissue injury model in which GI motility, systemic inflammation and wound fluid can be analyzed.
A non-narcotic murine trauma model was developed by the subcutaneous dorsal trans-implantation of a devitalized donor syngeneic harvested tissue-bone matrix (TBX), which was precisely adjusted to % total body weight and studied after 21 h. Gastrointestinal transit histograms were plotted after the oral administration of non-digestible FITC-dextran and geometric centers calculated. Organ bath evaluated jejunal circular muscle contractility. Multiplex electrochemiluminescence measurements of serum and TBX wound fluid inflammatory mediators were performed.
Increasing TBX amounts progressively delayed transit, whereas TBX heat denaturation or decellularization prevented ileus and death. In the TBX(17.5%) model, jejunal muscle contractility was suppressed and a systemic inflammatory response developed as significant serum elevations in IL-6, keratinocyte cytokine and IL-10 compared to sham. In addition, inflammatory responses within the wound fluid showed elevated levels of preformed IL-1β and TNF-α, whereas, 21 h after implantation IL-1β, IL-6 and keratinocyte cytokine were significantly increased in the wound.
CONCLUSIONS & INFERENCES: A novel donor tissue-bone matrix trauma model was developed that is precisely adjustable and recapitulates important clinical phenomena. The non-narcotic model demonstrated that increasing tissue injury progressively caused ileus, initiated a systemic inflammatory response and developed inflammatory changes within the wound.
创伤是导致死亡的主要原因，尽管肠道被认为是创伤后全身炎症反应综合征和多器官衰竭的“动力源”，但对胃肠道（GI）的研究却很少。我们的目的是创建一个精确可控的组织损伤模型，在该模型中可以分析 GI 蠕动、全身炎症和伤口液。
通过将非麻醉性同种异体供体组织-骨基质（TBX）的去活组织皮下背部移植，开发了一种非麻醉性的小鼠创伤模型，该模型精确调整到总体重的 %，并在 21 小时后进行研究。在口服不可消化的 FITC-右旋糖后绘制胃肠道转运直方图，并计算几何中心。器官浴评估空肠环形肌肉收缩性。通过多重电化学发光测量血清和 TBX 伤口液炎症介质。
TBX 量的增加逐渐延迟了转运，而 TBX 热变性或去细胞化可防止肠梗阻和死亡。在 TBX（17.5%）模型中，空肠肌肉收缩力受到抑制，与假手术相比，血清中白细胞介素 6、角质形成细胞细胞因子和白细胞介素 10 显著升高，出现全身炎症反应。此外，伤口液中的炎症反应显示出预先形成的白细胞介素 1β和肿瘤坏死因子-α水平升高，而在植入后 21 小时，伤口中的白细胞介素 1β、白细胞介素 6 和角质形成细胞细胞因子显著增加。
开发了一种新的供体组织-骨基质创伤模型，该模型可精确调节，并再现重要的临床现象。非麻醉模型表明，组织损伤的增加逐渐导致肠梗阻，引发全身炎症反应，并在伤口内引起炎症变化。
