Abstract
Background Chelerythrine (CHE) is a benzophenanthridine alkaloid that is a potent, selective,
and cell-permeable protein kinase C inhibitor. The purpose of the present study was
to examine the effect of CHE on intestinal recovery and enterocyte turnover after
intestinal ischemia-reperfusion (IR) injury in rats.
Methods Male Sprague-Dawley rats were divided into four experimental groups: (1) sham rats
underwent laparotomy, (2) sham-CHE rats underwent laparotomy and were treated with
intraperitoneal CHE; (3) IR-rats underwent occlusion of both superior mesenteric artery
and portal vein for 30 minutes followed by 48 hours of reperfusion, and (4) IR-CHE
rats underwent IR and were treated with intraperitoneal CHE immediately before abdominal
closure. Intestinal structural changes, Park injury score, enterocyte proliferation,
and enterocyte apoptosis were determined 24 hours following IR. The expression of
Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real
Western blot and immunohistochemistry.
Results Treatment with CHE resulted in a significant decrease in Park injury score in jejunum
(threefold decrease) and ileum (twofold decrease), and parallel increase in mucosal
weight in jejunum and ileum, villus height in jejunum and ileum, and crypt depth in
ileum compared with IR animals. IR-CHE rats also experienced a significantly lower
apoptotic index in jejunum and ileum, which was accompanied by a lower Bax/Bcl2 ratio
compared with IR animals.
Conclusions Treatment with CHE inhibits programmed cell death and prevents intestinal mucosal
damage following intestinal IR in a rat.
Keywords
ischemia-reperfusion - intestine - chelerythrine - apoptosis
