Bacterial translocation in rats treated with simvastatin undergoing intestinal ischemia and reperfusion

Abstract

Purpose: To evaluate the anti-inflammatory effect of simvastatin in an experimental model of intestinal ischemia/reperfusion, as well as in the prevention of bacterial translocation.  Methods: We used Wistar rats, randomly allocated in 5 groups:  C (n=10) controls; S (N=10) Shan-operated; I/R (n=10) intestinal ischemia and reperfusion; S+Sim (n=7) sham treated with simvastatin and I/R+Sim (n=7) ischemia/reperfusion treated with simvastatin.   In the group S, a laparotomy and manipulation of intestinal loops were performed. In the groups I/R and I/R+Sim, the superior mesenteric artery was occluded with a vascular microclamp, the laparotomy was closed and reopened 60 minutes after for pull back the clamp. The reperfusion was confirmed by the return of the pulsation of the mesenteric arcade. The animals were sacrificed after 120 minutes of reperfusion. Simvastatin microemulsion (10mg/kg) was administered (gavage) 18 hs and 2 hours before the surgical procedure.  Blood was collected by cardiac puncture for measurement of TNF-?, IL-1?, IL-6 and IL-10. One gram of spleen, liver and mesenteric lymph nodes was harvested for culture in selective means for Gram (-) and Gram (+) bacteria. A sample of terminal ileum of each animal was harvested, fixed in formalin 10% and included in paraffin. Slices were stained with hematoxilin-eosin for morphometric measurement. The damages of the intestinal samples were examined in a blind way by an experienced pathologist, in agreement with microscopic criteria for levels of aggressions based previously on a grade system. ANOVA and the post-hoc Tukey test were used, considering  p<0,05 as significant. Results: We observed bacterial translocation to mesenteric lymph nodes, spleen, liver and blood in all animals submitted to I/R, being smaller in the group I/R treated with simvastatin than in controls. In the I/R group rats the values of pro-inflammatory cytokines were significantly higher, when compared to the I/R+Sim group rats. The I/R+Sim group rats showed higher levels of IL-10, when compared with the other groups (p<0.05). The ileal segments presented macroscopic dilation and intramural hemorrhage. The microscopy revealed intense mucosa lesion in the group I/R compared to the other groups. The  histopathologic findings of the I/R+Sim group rats were similar to that found in the groups C and S. Conclusion: The simvastatin contributed to reduce the bacterial translocation, the values of pro-inflammatory cytokine and to increase the levels of anti-inflammatory cytokine, preserving the integrity of the intestinal epithelium in an experimental model of ischemia/reperfusion.