Activated protein C attenuates intestinal mucosal injury after mesenteric ischemia/reperfusion

J Surg Res. 2008 Oct;149(2):219-30. doi: 10.1016/j.jss.2007.10.011. Epub 2007 Nov 21.


Background: Activated protein C (APC) is a serine protease with anticoagulant and ant-inflammatory activities. APC has been shown to attenuate deleterious effects of ischemia/reperfusion (I/R) injury in many organs. In this study, we aimed to investigate the effects of APC on intestinal mucosal injury induced by superior mesenteric occlusion.

Materials and methods: Male Wistar-albino rats were allocated into four groups: (1) sham-operated group, laparotomy without I/R injury (n = 12); (2) sham + APC group, identical to Group 1 except for APC treatment (n = 12); (3) I/R group, 60 min of ischemia followed by 3-h of reperfusion (n = 12); and (4) I/R + APC-treated group, 100 mug/kg injection of APC intravenously, 15 min before reperfusion (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale from 0 to 5, histopathologically, and by measuring activities of oxidative and antioxidative enzymes as well as nitrate/nitrite levels, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma levels of proinflammatory cytokines and D-dimer were measured. Animal survival was observed up to 1 wk.

Results: Intestinal mucosal injury scores were significantly decreased with APC administration (P < 0.05). APC treatment significantly reduced activities of oxidative enzymes and nitrate/nitrite levels in the intestinal tissues, and plasma levels of proinflammatory cytokines and D-dimer, and also significantly increased activities of antioxidative enzymes in the intestinal tissues (P < 0.05). Intestinal edema was significantly alleviated with APC treatment (P < 0.05). The survival rate of rats in the APC-treated group were significantly higher than that of the I/R-treated group (P < 0.05).

Conclusions: This study clearly showed that APC treatment significantly attenuated intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether APC has a useful role in reperfusion injury during particular surgeries in which I/R-induced organ injury occurs.

MeSH terms

  • Animals
  • Anticoagulants / therapeutic use*
  • Edema / prevention & control
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Glutathione / metabolism
  • Glutathione Reductase / metabolism
  • Interleukin-6 / blood
  • Intestinal Mucosa / injuries*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Malondialdehyde / metabolism
  • Mesenteric Artery, Superior
  • Mesenteric Vascular Occlusion / drug therapy*
  • Nitrates / metabolism
  • Nitrites / metabolism
  • Peroxidases / metabolism
  • Protein C / therapeutic use*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Tumor Necrosis Factor-alpha / blood
  • Warm Ischemia
  • Xanthine Oxidase / metabolism


  • Anticoagulants
  • Fibrin Fibrinogen Degradation Products
  • Interleukin-6
  • Nitrates
  • Nitrites
  • Protein C
  • Tumor Necrosis Factor-alpha
  • fibrin fragment D
  • Malondialdehyde
  • Peroxidases
  • Xanthine Oxidase
  • Glutathione Reductase
  • Glutathione