Nuclear factor-kappa B activation by edema inhibits intestinal contractile activity

作者：Uray Karen S^*; Wright Zachary; Kislitsyna Karina; Xue Hasen; Cox Charles S Jr

来源：Critical Care Medicine, 2010, 38(3): 861-870.

DOI：10.1097/CCM.0b013e3181ce4aaa

• edema
• intestinal contractile activity
• smooth muscle
• nuclear factor-kappa B
• ileus

Objective: 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.
Design: Randomized animal study.
Setting: University laboratory.
Subjects: Male Sprague-Dawley rats, weighing 250-350 g.
Intervention: 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.
Measurements and Main Results: 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-kappa B in edema-induced intestinal dysfunction. Nuclear factor-kappa B deoxyribonucleic acid binding activity was significantly increased in edematous intestinal smooth muscle compared with controls. Inhibition of nuclear factor-kappa B activation blocked edema-induced decreases in basal intestinal contractile activity. Inhibition of nuclear factor-kappa B activation also attenuated edema-induced decreases in myosin light-chain phosphorylation.
Conclusions: We conclude that intestinal edema activates nuclear factor-kappa B, which, in turn, triggers a gene regulation program that eventually leads to decreased myosin light-chain phosphorylation and, thus, decreased intestinal contractile activity. (Crit Care Med 2010; 38: 861-870)

• 出版日期2010-3