Role Of Human Adipose-derived Mesenchymal Stem Cells In Hepatocellular Inflammatory Injury In Rats With Acute Hepatic Failure And Its Mechanism

【Objective】To investigate the role and molecular mechanism of human adipose-derived mesenchymal stem cells(h ADSC)in hepatocellular inflammatory injury in rats with acute hepatic failure.【Methods】The frozen human adipose-derived cells were resuscitated,then we identificated its surface molecular antigen,its potential of differentiation into adipogenic and osteogenic.cells was also identificated.The healthy grade SD rats(180-200g)were used as the research object,a liver failure model was established by injecting D-gal(dose:1.4g/kg)intraperitoneally in one-time,Then the rats were divided into three groups(group A: normal control group;group B: PBS group;group C: h ADSC group).The same amount of PBS or h ADSCs(about 3.0×106 cells)was injected through the tail vein.Six rats were sacrificed at 1,3 and 7 days after modeling.The changes of serum ALT and AST were observed.Serum levels of inflammatory cytokines-10 and tumor necrosis factor alpha were measured by enzyme linked immunosorbent assay.The expression of NF-κB in liver tissue was detected by western blot.At last,statistical software processes the data and concludes.【Results】(1)The resuscitated frozen human adipose-derived mesenchymal stem cell can highly express CD90、CD105 and lowly express HLA-DR、CD34,and has potential of differentiation into adipogenic and osteogenic.cell.Twelve hours after transplantation,DAPI-h ADSCs were observed by Inverted phase contrast microscope in liver and kidney tissues.(2)Injecting D-gal(dose:1.4g/kg)intraperitoneally in one-time could successfully construct rat model of liver failure.The level of serum ALT and AST in PBS group was significantly higher than that in normal control group(P <0.05).The liver tissue was pale and hepatocytes were vacuolar degeneration and necrosis,inflammatory cells were infiltrated in the portal area,liver sinus was congested and liver lobular structure was damaged seriously.(3)The levels of ALT and AST in the serum of rats in the h ADSC group were significantly lower than those in the PBS group(P <0.05),and the differences were statistically significant.The results of HE staining showed that the hepatocellular degeneration,necrosis and infiltration of inflammatory cells in h ADSC group were significantly improved compared with those in PBS group.The levels of serum TNF-a andIL-10 in h ADSC group were obviously lower than those in PBS group(P <0.05).The expression of NF-κB protein in the nucleus of PBS group was up-regulated,while the nuclear factor(NF-κB)in h ADSC group was inhibited obviously.【Conclusion】Human adipose tissue-derived mesenchymal stem cells can inhibit the inflammatory response of rats with hepatic failure,reduce liver tissue inflammatory injury and promote the recovery of liver function.Inhibition of NF-κB into the nucleus may be important in this process.