Comparison of Intestinal Warm Ischemic Injury in PACAP Knockout and Wild-Type Mice |
| |
Authors: | Andrea Ferencz Peter Kiss Gyorgy Weber Zsuzsanna Helyes Norihito Shintani Akemichi Baba Dora Reglodi |
| |
Institution: | (1) Department of Surgical Research and Techniques, University of Pecs Medical School, Kodaly Zoltan Street 20, 7624 Pecs, Hungary;(2) Department of Anatomy, University of Pecs Medical School, Kodaly Zoltan Street 20, 7624 Pecs, Hungary;(3) Department of Pharmacology and Pharmacotherapy, University of Pecs Medical School, Kodaly Zoltan Street 20, 7624 Pecs, Hungary;(4) Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan |
| |
Abstract: | Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in the gastrointestinal tract and plays a central role
in the intestinal physiology, mainly in the secretion and motility. The aim of our study was to compare the ischemic injury
in wild-type and PACAP-38 knockout mice following warm mesenteric small bowel ischemia. Warm ischemia groups were designed
with occlusion of superior mesenteric artery for 1, 3, and 6 h in wild-type (n = 10 in each group) and PACAP-38 knockout (n = 10 in each group) mice. Small bowel biopsies were collected after laparotomy (control) and at the end of the ischemia periods.
To determine oxidative stress parameters, malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD)
were measured. Tissue damage was analyzed by qualitative and quantitative methods on hematoxylin/eosin-stained sections. In
PACAP-38 knockout animals, tissue MDA increased significantly after 3 and 6 h ischemia (133.97 ± 6,2; 141.86 ± 5,8) compared
to sham-operated (100.92 ± 3,6) and compared to wild-type results (112.8 ± 2,1; 118.4 ± 1.03 μmol/g, p < 0.05). Meanwhile, tissue concentration of GSH and activity of SOD decreased significantly in knockout mice compared to
wild-type form (GSH, 795.97 ± 10.4; 665.1 ± 8,8 vs. 893.23 ± μmol/g; SOD, 94.4 ± 1.4; 81.2 ± 3.9 vs. 208.09 ± 3,7 IU/g). Qualitative
and quantitative histological results showed destruction of the mucous, submucous layers, and crypts in knockout mice compared
to wild-type tissues. These processes correlated with the warm ischemia periods. Our present results propose an important
protective effect of endogenous PACAP-38 against intestinal warm ischemia, which provides basis for further investigation
to elucidate the mechanism of this protective effect. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|