| Objectives: Sepsis is an infection-induced inflammatory syndrome that ultimately leads to organ dysfunction. Severe sepsis is very common in ICU and other critically ill patients, a large number of clinical patients die each year from sepsis. In recent ten years despite new antibiotics continuously appear, intensive care continuous improve, sepsis is still high mortality. From the 1970s, Most investigators would agree that severe sepsis is accompanied by the inability to regulate the inflammatory response, eventually leads to organ failure and death. Recently, statins, inhibit HMG-CoA oxidoreductase reaches the objective of cholesterol- lowering, have also been characterized by their immunomodulatory effects, as well as anti-inflammatory properties. In our tests, simvastatin is pretreated on the rat septic model which is made by caecum ligated and punctur(CLP), in order to observe simvastatin'curative effect in sepsis,then provide help for clinical diagnosis and treatment.Methods:Eighty clean and healthy female Wistar rats weight 200-250g, (supplied by the experimental animal center of Hebei medical university) were randomly divided into 4 groups. Group I: healthy control group(8 rats); group II: sham operation group(24 rats); group III: model group(24 rats); groupⅣ: model group pre-treated by simvastin(24 rats). Except healthy control group,other groups were divided into three subgroups according to the time of drawing blood(6h, 24h and 48h), the number of each subgroup is 8. The septic models were made by caecum ligation and puncture after treatment for 2 weeks. Rats appeared mental burnout, the abdominal distension, restlessness, shiver, canthal secretion increased, hairs in disorder, rectal temperature raise or lower 1℃as the symbol of success. The rats in groupⅣwere administrated with simvastatin (20mg/kg.day)by continuously, once a day. The other three groups were given normal saline of the same volume via gastric tube for 2 weeks. The blood speciemens of group I were taken after simvastain for 2 weeks. The blood speciemens of group II, group III and groupⅣwere taken after operation for 6h,24h,48h respectively. The values of GST and GLDH in the blood speciemen were measured by means of enzyme-linked immuno sorbent assay (ELISA).Results:1 The general performance of rats: The rats of group III and groupⅣcould drink water freely after operation for 2~3h, rats appeared mental burnout, the abdominal distension, restlessness, shiver, canthal secretion increased, hairs in disorder for 6~8h, Measuring rectal temperature by electronic thermometer, these were risen or reduced 1℃. The rats of group II could drink water freely after sham operation for 2~3h, without any abnormal condition.2 GST:Both of the values of GST in group III and groupⅣprogressively increased significantly after CLP; Comparison of each group by the time of drawing blood, the difference between group I and group II was not significant. GST in group III was higher than group I (P<0.05), the difference was significant; group III was higher than group II (P<0.05), the difference was significant; group IV was higher than group I (P<0.05), the difference was significant; group IV was higher than group II (P<0.05), the difference was significant; group III was higher than group IV (P<0.05), the difference was significant.3 GLDH: Both of the values of GLDH in group III and groupⅣprogressively increased significantly after CLP; Comparison of each group by the time of drawing blood, the difference between group I and group II was not significant. GLDH in group III was higher than group I (P<0.05), the difference was significant; group III was higher than group II (P<0.05), the difference was significant; group IV was higher than group I (P<0.05), the difference was significant; group IV was higher than group II (P<0.05), the difference was significant; group III was higher than group IV (P<0.05), the difference was significant.Conclusions: 1 The septic rat model could be made successfully by CLP.2 The values of GST and GLDH of the septic rats in serum increase significantly. It pointe that sepsis causes liver microcirculation perfusion inadequacy, causes liver cell ischemia and hypoxia, eventually damages liver cell and mitochondria.3 Simvastatin could lower the values of serum GST and GLDH of septic rats. Then we can presume that simvastatin can improve the septic liver microcirculation perfusion. But it cannot completely treatment of sepsis. |
