- 作者：Takeshi Takano ; M.D.&lowast ; ; Yoshikazu Yonemitsu ; M.D. ; F.A.H.A.&dagger ; ; yonemitu@med.kyushu-u.ac.jp ; Satoru Saito ; Ph.D.&dagger ; ; Hiroyuki Itoh ; M.D. ; Ph.D.&lowast ; ; Toshihiro Onohara ; M.D. ; Ph.D.&lowast ; ; Atsushi Fukuda ; M.D. ; Ph.D.&lowast ; ; Maki Takai ; M.D.&lowast ; ; Yoshihiko Maehara ; M.D. ; Ph.D. ; F.A.C.S.&lowast ;
- 关键词：ischemia-reperfusion injury ; somatostatin analogue ; free-radical scavenger ; heme oxygenase-1
- 刊名：Journal of Surgical Research
- 出版年：2012
- 期刊代码：299_00224804
- 类别：med
- 出版时间：15 June, 2012
- 卷：175
- 期：2
- 页码：350-358
- 文件大小：1054 K
Background
Intestinal damage after ischemia followed by revascularization, referred to as 鈥渋schemia-reperfusion (I/R) injury,鈥?is a devastating complication that can occur after acute superior mesenteric obstruction, or after both elective and emergent abdominal aortic surgery. Once an entire layer of intestine is involved in severe ischemia, the mortality rate reaches 90%; no effective medical treatment has been reported to date. Here, we demonstrate that a somatostatin analogue, octreotide, but not a free-radical scavenger, MCI-186, prevented death due to surgically induced intestinal I/R injury in rats.Methods
Superior mesenteric artery (SMA) of Male Sprague-Dawley rats, that received MCI-186聽or octreotide, was surgically clamped, and then the clips were removed and SMA blood flow restored. Survival was assessed, and blood and small intestine were subjected to cell count, enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry.
Results
Of interest, pretreatment with octreotide, but not with MCI-186, just before induced intestinal ischemia prompted the early expression of heme oxygenase-1 (HO-1) protein-associated accumulation of CD68-positive cells, a possible cellular source of HO-1. Inversely, the administration of tin protoporphyrin IX (SnPPN), a specific inhibitor of HO-1, completely abolished the therapeutic effects of octreotide, indicating that the favorable effects of octreotide against intestinal I/R injury is predominantly dependent on the early induction of HO-1.
Conclusions
These results suggest that a somatostatin analogue may be useful in leading to an improvement of the prognosis of patients with intestinal I/R injury in the clinical setting.