Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/reperfusion injury to the rat intestinal epithelium

Background and aims—Injuries caused by ischaemia and ischaemia/reperfusion in the small intestine have been widely accepted as resulting in necrosis. The aim of this study was to ascertain whether apoptosis also occurs. Methods—Intestinal epithelium from rats subjected to ischaemia (15-90 minutes) and ischaemia/reperfusion (15 minutes ischaemia followed by 15-75 minutes of reperfusion) was studied using histological, immunohistochemical, and molecular biological methods as well as FACS. Results—Mucosal injury was induced by both ischaemia and ischaemia/reperfusion. Detachment of epithelial cells from the villous stroma was an early morphological change indicating mucosal injury. More than 80% of the detached cells exhibited characteristic morphological features of apoptosis (condensation of chromatin and nuclear fragmentation). The remainder demonstrated necrotic features. The apoptotic cells eventually underwent spontaneous degeneration with membrane rupture, a process morphologically identical to necrosis. DNA fragmentation was also confirmed by immunohistochemical methods and agarose gel electrophoresis. Conclusion—Apoptosis is a major mode of cell death in the destruction of rat small intestinal epithelial cells induced by ischaemia and ischaemia/reperfusion injury. Disruption of epithelial cell-matrix interactions ("anoikis") may play an important part in induction of apoptosis in detached enterocytes. Keywords: ischaemia; reperfusion; apoptosis; necrosis; enterocyte; rat