Protective role of heme oxygenase 1 in the intestinal tissue injury in hemorrhagic shock in rats.
Heme oxygenase (HO) 1 is inducible by a variety of oxidative stress and is thought to play an important role in the protection of tissues from oxidative injuries. Because hemorrhagic shock (HS) is an oxidative stress that results in tissue injury, we examined in this study the role of HO-1 induction in intestinal tissue injuries in a rat model of HS. The levels of HO-1 were significantly increased after HS both at transcriptional and protein levels in mucosal epithelial cells in the duodenum, jejunum, and colon, whereas their expression in the ileum was hardly detectable and not increased at all by the treatment. In contrast, HS-induced mucosal inflammation and apoptotic cell death in the duodenum, jejunum, and colon were far less than those observed in ileum as judged by the levels of expression of TNF-alpha, iNOS, activated caspase 3, and Bcl-2. Of note, inhibition of HO activity by tin-mesoporphyrin resulted in an aggravation of HS-induced tissue inflammation and apoptotic cell death. These findings indicate that HO-1 expression in the intestine is regulated in a highly site-specific manner after HS, and that HO-1 induction plays a fundamental role in protecting mucosal cells of the intestine from oxidative damages induced by HS.
Inoue
Kazuyoshi
K
Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama, Japan.
Takahashi
Toru
T
Uehara
Kenji
K
Shimuzu
Hiroko
H
Ido
Kana
K
Morimatsu
Hiroshi
H
Omori
Emiko
E
Katayama
Hiroshi
H
Akagi
Reiko
R
Morita
Kiyoshi
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015152:Blotting, Northern; D015870:Gene Expression; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply / Q000187:drug effects; D008297:Male; D008665:Metalloporphyrins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008665:Metalloporphyrins; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; C055421:tin mesoporphyrin; D006418:Heme; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051547:Heme Oxygenase-1