Effect Of Curcumin On Serum Levels Of IL-18 In Rats Sepsis Induced By LPS

Objective:Sepsis has become a widespread and very complex issue for modern critical care medicine.It is undoubtedly of great theoretical and clinical significance that we should strengthen the study of sepsis and explore new treatments and drugs in our work.The objectives of our study were to investigate whether curcumin had treatment of sepsis and understand the relationship between 1L-18 and organ damage caused by sepsis and comprehend the effect of curcumin on serum levels of IL-18 in sepsis.Method:60 clean Wister male rats were randomly divided into the control group (C), the sepsis model induced by LPS group (LPS), the curcumin treatment group (LPS+Cur). There were 6 rats in the C group,24 rats in the LPS group and the LPS+Cur group respectively.Sepsis model was made by Escherichia coli LPS 5mg/kg through intraperitoneal injection. Curcumin was dissolved in 50% dimethyl sulfoxide (DMSO). The C group was injected intraperitoneally with normal saline in the test day.4h after the experiment began, C groups blood was obtained from the inferior vena cava, then the rats of the group were killed by cervical dislocation and their liver and kidney tissues were reserved. In the experiment day, the LPS group was injected intraperitoneally LPS 5mg/kg+50% DMSO, the LPS+Cur group was injected intravenously curcumin 50mg/kg immediately followed by intraperitoneal injection of LPS 5mg/kg.4h,8h,12h and 24h after the experiment began, these two groupsblood was obtained from the inferior vena cava, respectively, then the rats of these two groups were killed by cervical dislocation and their liver and kidney tissues were reserved, each of 6 rats each time point.After centrifugation, the remaining plasma was measured in serum ALT, AST, Cre, BUN, TNF-a and IL-18 values.The data expressed as means±standard deviation(X±s).p value less than 0.05 was considered significant. The liver and kidney tissues were fixed in 10% neutral formaldehyde,then dehydrated with ethanol, transparencied, dip wax, embeded, cut into slices 2μm.After routine HE staining,the samples were made histological observation under the light microscopy. Results:1. Compared with the C group, ALT,AST,Cre,BUN levels of the LPS group were significantly increased at each time point(P<0.01, statistically significant),all reached a peak at 8h.TNF-a and 1L-18 levels of the LPS group were significantly increased in 4h,8h,12h(P<0.01.statistically significant),both peaked at 8h,approached to normal levels at 24h (P>0.05,no statistically significant).Pathological changes in liver tissues were mainly diffuse vacuolar degeneration,scattered eosinophilic degeneration, scattered acute and chronic inflammatory cells infiltration of hepatic sinusoids,focal necrosis of liver cells,small abscess fonnation.Pathological changes in kidney tissues were mainly diffuse infiltration of neutrophils in glomerular, part of segmental glomerular necrosis, balloon dilatation, diffuse tubular brush border loss, part of the tube formation, local severe vacuolar degeneration.Pathological change in liver and kidney tissues at 8h was the severest change that is in accordance with the trend of serum biochemical and immune parameters.2. Compared with the LPS group,ALT,AST,Cre,BUN levels of the LPS+Cur group were significantly decreased at each time point (P<0.05, statistically signifi-cant).TNF-a levels of the LPS+Cur group were significantly decreased in 4h,8h, 12h(P<0.01, statistically significant);no significant difference at 24h (P> 0.05, no statistically significant).1L-18 levels of the LPS+Cur group were significantly decreased in 4h,8h,12h,24h(P<0.01, statistically significant).Pathological changes in liver tissues of the LPS+Cur group significantly reduced in comparision with the LPS group, just showed scattered acute and chronic inflammatory cells infiltration,no abscess and necrosis.Pathological changes in kidney tissues of the LPS+Cur group were mainly infiltration of neutrophils in part of the glomeruli and interstitium, less than those in the LPS group, no necrosis and shedding.Conclusions:1. The most obvious inflammatory response of sepsis induced by LPS is at 8h, meanwhile, the organ dysfunction and pathological damage by sepsis is the most serious too.2. Excessive production of 1L-18 is closely associated with the acute liver and kidney damage caused by sepsis.The higher levels of IL-18 serum, the more serious injury of function and pathology of liver and kidney.IL-18 can be used as to determine organ damage caused by sepsis detection marker.3. Curcumin inhibits excessive production of TNF-αand IL-18 and reduces the excessive inflammatory response in sepsis.It could protect organ function from injury caused by sepsis through the effect of immune regulation itself.