Venous congestion induces mucosal apoptosis via tumor necrosis factor-alpha-mediated cell death in the rat small intestine

Tissue and organic venous congestion is a common pathophysiologic phenomenon. However, it is unclear whether venous congestion induces small-intestinal mucosal apoptosis. The aim of this study was to investigate whether venous congestion, or congestion followed by re-outflow, induced small-intestinal mucosal apoptosis, and whether tumor necrosis factor-alpha is involved in this apoptosis. Small-intestinal venous congestion was induced in rats by occlusion of the superior mesenteric vein with a micro-bulldog clamp. At the end of the congestive period, the clamp was released to facilitate congestion followed by re-outflow. The rats were injected with a neutral anti-tumor necrosis factor-alpha antibody (0.15 mg/kg) via the jugular vein for 30 min before venous congestion or congestion followed by re-outflow. Intestinal mucosal apoptosis was evaluated and tumor necrosis factor-alpha was assayed. The amounts of caspase-8, caspase-3, and cytochrome c were determined by Western blot analysis. Our results showed that venous congestion and congestion followed by re-outflow significantly increased mucosal apoptosis, the amount of mucosal tumor necrosis factor-alpha, and the levels of caspase-8 cleavage and caspase-3 activation, but did not induce cytochrome c release from mitochondria to the cytosol. Pretreatment with an anti-tumor necrosis factor-alpha antibody significantly reduced mucosal apoptosis after intestinal congestion or congestion followed by re-outflow. The present results support the view that venous congestion and congestion followed by re-outflow induce mucosal apoptosis in the rat small intestine, and show that the apoptosis occurs partly via tumor necrosis factor-alpha-mediated cell death.