Protective Effect Of Simvastatin On Intestinal Injury In Mice With Sepsis

Objective:Sepsis is a life-threatening organ failure caused by an uncontrolled reaction to infection.In sepsis,the intestine is an important damaged organ which can exacerbation sepsis response,leading to the death of the patient at the same time.In addition to the role of simvastatin in regulating blood lipids,recent studies have shown that it can regulate body immunity and stabilize endothelium.It has anti-inflammatory effects as well.In this study,simvastatin was administered by intraperitoneal injection to discuss the protective effect of simvastatin on intestinal injury in sepsis mice induced by cecal ligation and puncture.Methods: 72 male C57BL/6 mice were randomly divided into the following 3 groups(24/group): Sham group(sham group),SEP group(sepsis group),SIM group(sepsis +simvastatin therapy group).The cecal ligation and puncture method(CLP)was used to construct a mouse model of sepsis.The sham group did not need cecal ligation and perforation,and only performed laparotomy.The mice were sacrificed at 12 h and 24 h after the model was successfully established.The intestinal tissues were taken to observe the pathological changes of the intestine;the intercellular cell adhesion molecule-1(ICAM-1)and and myeloperoxidase(MPO)concentrations of the intestinal tissue was determined by enzyme-linked immunosorbent assay(ELISA).Results: Under the light microscope,the villi in the small intestine of the Sham group were arranged neatly,the intestinal mucosal morphology was basically normal,and there was no significant difference in the pathological appearance at 12 h and 24 h after modeling.In the SEP group,thinne intestinal wall,villous edema,fuzzy villi structure,loss and necrosis of intestinal,epithelium inflammatory cell infiltration was observed.The damage is more severe in SEP24 h mice.The structure of the small intestine wall in the SIM group was partially destroyed,and the degree of mucous membrane edema was light.Only a small amount of inflammatory cells infiltrated,and the damage is less compared with the same observation point of SEP group.Compared with Sham group,ICAM-1 and MPO in the small intestine homogenate of SEP group were significantly higher(P<0.05).Compared with SEP group,ICAM-1 and MPO in the small intestine homogenate of SIM group were significantly lower(P<0.05).Conclusion: Simvastatin has a protective effect on intestinal injury in sepsis mice,and its mechanism is related to inhibition of PMN aggregation and down-regulation of ICAM-1 levels.