Histochemistry and Cell Biology

, Volume 123, Issue 3, pp 249–261 | Cite as

Induction of cell death in rat small intestine by ischemia reperfusion: differential roles of Fas/Fas ligand and Bcl-2/Bax systems depending upon cell types

  • Shucai An
  • Yoshitaka Hishikawa
  • Takehiko KojiEmail author
Original Paper


Although ischemia reperfusion (I/R) induces apoptotic damage of mammalian small intestine, the molecular mechanism is largely unknown. We investigated the appearance of apoptosis at various time-points (0–24 h) of reperfusion after 1-h ischemia and the expression of various apoptosis-related proteins, such as Bcl-2, Bax, Fas, Fas ligand (FasL), activated caspase-3, and cytochrome c, immunohistochemically in rat small intestine. As assessed by TUNEL and electron microscopy, apoptotic cells were increased at 3 h of reperfusion in all intestinal parts (villous epithelium, crypt epithelium, and stroma of intestine). Moreover, the TUNEL-positive cells in the stroma were later identified as T cells. The expression of Fas and FasL as well as activated caspase-3 was markedly increased at 3 h of reperfusion in the stroma. In the villous epithelium, a transient decrease in Bcl-2 expression was found while in the crypt epithelium, Fas expression was induced. Finally, intraperitoneal injection of leupeptin (an SH-protease inhibitor) after I/R resulted in a significant inhibition of the induction of apoptosis in the stroma and crypt epithelium. Our results indicate that the triggering molecules of apoptosis in the I/R rat small intestine may vary depending on cell type and that the use of a broad-spectrum protease inhibitor may reduce intestinal damage.


Ischemia-reperfusion injury Apoptosis Apoptosis-related proteins Leupeptin Rat small intestine 



This study was supported in part by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Science, Sports, and Culture (no. 15390058 to T.K.). The authors thank Mr. Takashi Suematsu for this excellent ME techniques assistance.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Division of Histology and Cell Biology, Department of Developmental and Reconstructive MedicineNagasaki University Graduate School of Biomedical SciencesSakamoto, NagasakiJapan

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