Protective Effects Of Adiponectin On Liver Dysfunction In Septic Rats

Objective: In this study, sepsis was induced by cecal ligation and puncture(CLP) in wistar male rats in order to invest the dynamic changes of serum procalcitonin(PCT),markers of liver function(ALT, AST, TBIL), liver tissue inflammatory cytokines(TNF-α, IL-6) and liver tissue pathological morphological in different experimental time point. Finally, we evaluated the protective effects of adiponectin on sepsis-induced liver dysfunction and its possible mechanisms.Method: Fifty-four Wister rats were randomly divided into three groups, which were sham-operated group(Sham, n=18), CLP group(CLP, n=18) and adiponectin intervention group( APN+CLP, n=18), then every group was divided into(3h, 6h, 12h)3 sub-groups according to the different experimental time point(each group six).Sham group rats underwent laparotomy, but without cecal ligation and puncture, CLP group and APN+CLP group were made sepsis animal models by cecal ligation and puncture, APN+CLP group were immediately intraperitoneal injected adiponectin600 ug /100 g after CLP. Respectively, the samples of blood and liver tissues were harvested in each time point. Serum procalcitonin, markers of liver function and liver tissue inflammatory cytokines(TNF-α, IL-6) were examined by ELISA, pathological morphological of liver tissues by HE staining.Results: The levels of markers of liver function(ALT, AST, TBIL), CLP group and APN+CLP group were significantly higher than Sham group(P <0.05), but the APN+CLP group was lower than CLP group(P <0.05). The levels of serum PCT after3 h were not statistical significance in different experimental groups(P>0.05), after 6h CLP group was significantly higher than Sham group(P <0.05), after 12 h continued to rise, but APN + CLP group was lower than CLP group at 6h、12h. The levels of liver inflammation factor(TNF-α, IL-6), CLP group and APN+CLP group were significantly higher than Sham group at all time points(P <0.05), but APN + CLP group was significantly lower than CLP group(P <0.05). The pathological morphological changes of liver were observed under the microscope, After 3 h, liver cells of Sham group arranged regularly, their morphology is a polygon, the cell nucleus were located in the center of cells, assumes the circular, cytoplasmic evenly without impurities; CLP group can be observed in normal lobular architecture,occasional nucleus occurred pycnosis, dissolution and fracture phenomenon, granular hemosiderin can be seen in the individual cells; Compared with CLP group,APN+CLP group liver damage reduced slightly, but not significantly; After 12 h,liver tissue visible changes in the following form:compared with the postoperative 3 h,morphology of liver has no obvious change, liver pathological structure change wereobvious abnormal in CLP group, liver cell size, irregular, some cells visible swelling degeneration, and even individual cell necrosis, visible multiple cell nucleus pycnosis,dissolved and fracture phenomenon, even visible phenomenon of liver cell regeneration, some cell nucleus appeared double-nuclei, APN+CLP group was lighter significantly than CLP group, but still visible lesions of different level; Each liver tissue structure change between 3 h and 12 h after 6h. Pathological morphological changes of liver in different experimental group at each time point suggested,the degree of liver inflammation was reduced after giving adiponectin, in other words,APN has protective effect on the liver.Conclusion: Adiponectin could exert protective effects on sepsis-induced liver dysfunction in septic rats, Which may be through reducing liver tissue inflammatory cytokines(TNF-α, IL-6) levels.