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Updated: Aug 23, 2026

Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Protective effect of endogenous PPARgamma against acute gastric mucosal lesions associated with ischemia-reperfusion
Koichiro Wada1, Atsushi Nakajima, Hirokazu Takahashi
1Gastroenterology Division, Thorn 1419, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St., Boston, MA 02115, USA.
Abstract:
Acute gastric mucosal lesions (AGMLs) are an important cause of gastrointestinal bleeding. Herein, we demonstrate that peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of a nuclear receptor family, functions as an endogenous anti-inflammatory pathway in a murine model of AGML induced by ischemia-reperfusion (I/R). Treatment with specific PPARgamma ligands such as BRL-49653, pioglitazone, or troglitazone was examined in a model of AGML induced by I/R. PPARgamma-deficient and wild-type mice were also examined for their response to I/R in stomach. Specific PPARgamma ligands exhibited dramatic and rapid protection against AGML formation associated with I/R in mice in a dose-dependent manner. In contrast, the AGML induced by I/R in PPARgamma-deficient mice was more severe than that observed in wild-type mice. Administration of the PPARgamma ligand significantly inhibited the upregulation of TNF-alpha, ICAM-1, inducible nitric oxide synthase, apoptosis, and nitrotyrosine formation induced by I/R in the stomach. These data indicate that an endogenous pathway associated with PPARgamma plays an important role in the pathogenesis of I/R-associated injury in the stomach.
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