Pyrrolidine dithiocarbamate protects the small bowel from warm ischaemia/reperfusion injury of the intestine: the role of haem oxygenase

被引:14
作者
Mallick, Ismail H.
Winslet, Marc C.
Seifalian, Alexander M.
机构
[1] UCL, Acad Div Surg & Intervent Sci, Gastrointestinal & Hepatobiliary Res Unit, London NW3 2PF, England
[2] Royal Free Hampstead NHS Trust Hosp, Dept Surg, London NW3 2PF, England
关键词
haem oxygenase; intestine; ischaemia/reperfusion injury; microcirculation; multiple organ failure; pyrrolidine dithiocarbamate (PDTC);
D O I
10.1042/CS20060119
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
IR (ischaemia/reperfusion) injury of the intestine occurs commonly during abdominal surgery. We have previously shown that PDTC (pyrrolidine dithiocarbamate), an HO-1 (haem oxygenase-1) donor, improves intestinal microvascular perfusion. In the present study, we have investigated the effects of PDTC on the intestinal microcirculation following IR (ischaemia/reperfusion) injury of the intestine. Male Sprague-Dawley rats (n = 72) were randomly assigned to four groups (n = 18/group): (i) sham-operated group, who underwent laparotomy without induction of IR of the intestine; (ii) IR group, who were subjected to 30 min of superior mesenteric artery occlusion and 2 h of reperfusion; (iii) PDTC + IR group, who received PDTC prior to IR; and (iv) ZnPP group, who received the HO-I inhibitor ZnPP (zinc protoporphyrin) followed by procedures as in group (iii). The ileum was evaluated for changes in tissue cytochrome c oxidase redox status, RBC (red blood cell) dynamics and leucocyte-endothelial interactions. The expression of HO-1 in the ileal tissue was examined at the end of the reperfusion. PDTC significantly improved the intestinal tissue oxygenation, mucosal perfusion index and RBC velocity compared with the IR and ZnPP groups. PDTC also decreased the leucocyte-endothelial interactions (P < 0.05 compared with the IR and ZnPP groups). PDTC induced the expression of HO-1, whereas ZnPP abolished this effect.
引用
收藏
页码:373 / 380
页数:8
相关论文
共 32 条
[1]   Ischemia-reperfusion injury following superior mesenteric artery occlusion and strangulation obstruction [J].
Akcakaya, A ;
Alimoglu, O ;
Sahin, M ;
Abbasoglu, SD .
JOURNAL OF SURGICAL RESEARCH, 2002, 108 (01) :39-43
[2]  
[Anonymous], FREE RADICALS BIOL M
[3]  
BALLA G, 1992, J BIOL CHEM, V267, P18148
[4]   Heme oxygenase-1: Redox regulation and role in the hepatic response to oxidative stress [J].
Bauer, M ;
Bauer, I .
ANTIOXIDANTS & REDOX SIGNALING, 2002, 4 (05) :749-758
[5]  
BRUNE B, 1987, MOL PHARMACOL, V32, P497
[6]  
Chien S, 1982, Adv Shock Res, V8, P71
[7]  
CHIU CJ, 1970, ARCH SURG-CHICAGO, V101, P478
[8]  
CLASTER S, 1984, BLOOD, V64, P1079
[9]   Functional studies of the kidney of living animals using multicolor two-photon microscopy [J].
Dunn, KW ;
Sandoval, RM ;
Kelly, KJ ;
Dagher, PC ;
Tanner, GA ;
Atkinson, SJ ;
Bacallao, RL ;
Molitoris, BA .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2002, 283 (03) :C905-C916
[10]   Endotoxin related early neutrophil activation is associated with outcome after thoracoabdominal aortic aneurysm repair [J].
Foulds, S ;
Cheshire, NJ ;
Schachter, M ;
Wolfe, JH ;
Mansfield, AO .
BRITISH JOURNAL OF SURGERY, 1997, 84 (02) :172-177