Department of Pediatric Surgery, University of Texas Medical School at Houston, Houston, TX, USA.
Surgery. 2010 Jun;147(6):772-9. doi: 10.1016/j.surg.2009.11.014. Epub 2010 Jan 25.
Hydrostatic intestinal edema initiates a signal transduction cascade that results in smooth muscle contractile dysfunction. Given the rapid and concurrent alterations in the mechanical properties of edematous intestine observed with the development of edema, we hypothesize that mechanical forces may serve as a stimulus for the activation of certain signaling cascades. We sought to examine whether isolated similar magnitude mechanical forces induced the same signal transduction cascades associated with edema.
The distal intestine from adult male Sprague Dawley rats was stretched longitudinally for 2 h to 123% its original length, which correlates with the interstitial stress found with edema. We compared wet-to-dry ratios, myeloperoxidase activity, nuclear signal transduction and activator of transcription (STAT)-3 and nuclear factor (NF)-kappa B DNA binding, STAT-3 phosphorylation, myosin light chain phosphorylation, baseline and maximally stimulated intestinal contractile strength, and inducible nitric oxide synthase (iNOS) and sodium hydrogen exchanger 1-3 messenger RNA (mRNA) in stretched and adjacent control segments of intestine.
Mechanical stretch did not induce intestinal edema or an increase in myeloperoxidase activity. Nuclear STAT-3 DNA binding, STAT-3 phosphorylation, and nuclear NF-kappa B DNA binding were significantly increased in stretched seromuscular samples. Increased expression of sodium hydrogen exchanger 1 was found but not an increase in iNOS expression. Myosin light chain phosphorylation was significantly decreased in stretched intestine as was baseline and maximally stimulated intestinal contractile strength.
Intestinal stretch, in the absence of edema/inflammatory/ischemic changes, leads to the activation of signaling pathways known to be altered in intestinal edema. Edema may initiate a mechanotransductive cascade that is responsible for the subsequent activation of various signaling cascades known to induce contractile dysfunction.
静水压力性肠水肿引发信号转导级联反应，导致平滑肌收缩功能障碍。鉴于水肿发展过程中观察到的水肿肠机械特性的快速和同时改变，我们假设机械力可能作为某些信号级联激活的刺激。我们试图研究是否类似幅度的机械力会诱导与水肿相关的相同信号转导级联。
将成年雄性 Sprague Dawley 大鼠的远端肠纵向拉伸 2 小时至其原始长度的 123%，这与水肿时发现的间质压力相关。我们比较了湿干比、髓过氧化物酶活性、核信号转导和转录激活因子（STAT）-3 和核因子（NF）-κB DNA 结合、STAT-3 磷酸化、肌球蛋白轻链磷酸化、基线和最大刺激肠收缩强度，以及诱导型一氧化氮合酶（iNOS）和钠氢交换器 1-3 信使 RNA（mRNA）在拉伸和相邻对照肠段中的表达。
机械拉伸不会引起肠水肿或髓过氧化物酶活性增加。核 STAT-3 DNA 结合、STAT-3 磷酸化和核 NF-κB DNA 结合在拉伸的肌层样本中显著增加。发现钠氢交换器 1 的表达增加，但 iNOS 的表达没有增加。肌球蛋白轻链磷酸化在拉伸肠中显著降低，基线和最大刺激肠收缩强度也降低。
在没有水肿/炎症/缺血变化的情况下，肠拉伸会导致已知在肠水肿中改变的信号通路的激活。水肿可能引发机械转导级联反应，负责随后激活各种已知导致收缩功能障碍的信号级联。
