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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Wu
Bin
B
Department of Internal Medicine, Saga Medical School, 5-1-1 Nabeshima, 849-8501, Saga, Japan.
Fujise
Takehiro
T
Iwakiri
Ryuichi
R
Ootani
Akifumi
A
Amemori
Sadahiro
S
Tsunada
Seiji
S
Toda
Shuji
S
Fujimoto
Kazuma
K
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D004792:Enzyme Precursors; D014409:Tumor Necrosis Factor-alpha; D045304:Cytochromes c; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases