The Research Of Survival Protection And Anti-inflammatory Effects Of 4EDB-1 On LPS-induced Sepsis In Mice

Objective:To study the effect of 4EDB-1(A sinomenine derivatives)on the survival,the fuction of liver and kidney and its anti-inflammatory effects of LPS-induced sepsis mice.Methods:1.Effects of 4EDB-1 on survival and liver and kidney function in mice(1)To observe and record the survival status and survival of mice for six days under different concentrations of drugs;(2)To detected the changes of liver and kidney function indexes such as ALT,AST,BUN,CREA by biochemical analyzer under different drug concentration and frequency of administration.2.Effects of 4EDB-1 on changes of inflammatory factors and phenotype of spleen macrophages(1)Using enzyme-linked immunosorbent assay(ELISA)to measure the levels of cytokines such as IL-6,TNF-and IL-10 in the blood and cell supernatant of mice;(2)Using flow cytometry to detect F4 / 80 + CD206 in mouse spleen cells to evaluate macrophage polarization.Results:1.The six days survival rate in the untreated group(LPS + NS group)was 20%;The rate of the 4EDB-1 experimental group(5 mg / kg,10 mg / kg)was 100%;while that of SIN-HCL(Sinomenine hydrochloride)experimental group(10mg / kg,15 mg / kg)mice was 80% survival rate and that of SIN-HCL group(5mg / kg)was only 60%.2.Compared with the control group and SIN-HCL groups,the levels of ALT,AST,CREA and BUN did not change significantly under different concentrations of4EDB-1 after 2 or 4 times(P>0.05).3.In vivo,experiments showed that compared with the untreated group,the levels of IL-6 and TNF-? in the blood of septic mice of 4EDB-1 experimental group(5mg/kg)were decreased(P<0.001);and the levels of IL-10 had significantly increased(P<0.001).In vitro,experiments indicated that when the 4EDB-1 concentration is 1,2,5 and 10 umol/L,the level of IL-6 in the supernatant than in the untreated group,were significantly decreased(P<0.01,P<0.05).When the concentration of 4EDB-1 is 2,5and 10 umol/L,TNF-? levels were obviously decreased(P<0.05,P<0.01),while the level of IL-10 was increased(P<0.01).4.Using measurement of the expression of F4/80 and CD206 in mouse spleen macrophages by flow cytometry,we found that after 4EDB-1 treatment,the CD206 expression of septic mouse was significantly higher than the untreated group(P<0.01).Conclusions:1.Compared with the SIN-HCL group,4EDB-1 showed better therapeutic effect at the same concentration,and had protective effect on septic mice.2.4EDB-1 has no obvious toxic effect on mice liver and kidney function in a short time,but its long-term effect remains to be investigated.3.4EDB-1 may promote the release of IL-10 and inhibit the release of inflammatory cytokines such as TNF-? and IL-6 by promoting the polarization of M2,which can reduce the inflammatory response.