Department of Pediatric Surgery, University of Texas Medical School at Houston, Houston, TX, USA.
Crit Care Med. 2010 Mar;38(3):861-70. doi: 10.1097/CCM.0b013e3181ce4aaa.
To investigate the molecular mechanisms leading to edema-induced decreases in intestinal smooth muscle myosin light-chain phosphorylation. Intestinal interstitial edema often develops during abdominal surgery and after fluid resuscitation in trauma patients. Intestinal edema causes decreased intestinal contractile activity via decreased intestinal smooth muscle myosin light-chain phosphorylation, leading to slower intestinal transit. Interstitial edema development is a complex phenomenon, resulting in many changes to the interstitial environment surrounding intestinal smooth muscle cells. Thus, the mechanism(s) by which intestinal edema development causes intestinal dysfunction are likely to be multifactorial.
Randomized animal study.
University laboratory.
Male Sprague-Dawley rats, weighing 250-350 g.
Studies were performed in a rat model in which a combination of mesenteric venous hypertension and administration of resuscitative fluids induces intestinal edema, mimicking the clinical setting of damage control resuscitation.
Microarray analysis of edematous intestinal smooth muscle combined with an in silico search for overrepresented transcription factor binding sites revealed the involvement of nuclear factor-kappaB in edema-induced intestinal dysfunction. Nuclear factor-kappaB deoxyribonucleic acid binding activity was significantly increased in edematous intestinal smooth muscle compared with controls. Inhibition of nuclear factor-kappaB activation blocked edema-induced decreases in basal intestinal contractile activity. Inhibition of nuclear factor-kappaB activation also attenuated edema-induced decreases in myosin light-chain phosphorylation.
We conclude that intestinal edema activates nuclear factor-kappaB, which, in turn, triggers a gene regulation program that eventually leads to decreased myosin light-chain phosphorylation and, thus, decreased intestinal contractile activity.
研究导致肠平滑肌肌球蛋白轻链磷酸化减少的水肿诱导机制。
肠间质水肿在腹部手术和创伤患者液体复苏后经常发生。肠水肿通过降低肠平滑肌肌球蛋白轻链磷酸化导致肠收缩活动减少，从而导致肠传输减慢。间质水肿的发展是一个复杂的现象，导致围绕肠平滑肌细胞的间质环境发生许多变化。因此，肠水肿发展导致肠功能障碍的机制可能是多因素的。
随机动物研究。
大学实验室。
雄性 Sprague-Dawley 大鼠，体重 250-350g。
在一种大鼠模型中进行了研究，该模型结合肠系膜静脉高压和复苏液的给予诱导肠水肿，模拟损伤控制性复苏的临床情况。
水肿肠平滑肌的微阵列分析结合计算机搜索转录因子结合位点的过度表达显示核因子-κB 参与水肿诱导的肠功能障碍。与对照组相比，水肿肠平滑肌中的核因子-κB 脱氧核糖核酸结合活性显著增加。核因子-κB 激活的抑制阻断了水肿诱导的基础肠收缩活动的减少。核因子-κB 激活的抑制也减轻了水肿诱导的肌球蛋白轻链磷酸化减少。
我们得出结论，肠水肿激活核因子-κB，进而触发基因调节程序，最终导致肌球蛋白轻链磷酸化减少，从而导致肠收缩活动减少。
