Interleukin-18 antisense oligodeoxynucleotide promotes hepatocyte regeneration of partial liver allograft / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of interleukin (IL)-18 ASPODN on regeneration of allogeneic partial liver graft in rats.</p><p><b>METHODS</b>Ninety donor SD rats and ninety recipient LEW rats were randomly divided into 3 groups 50% partial liver transplantation group (PLT group); PLT+IL-18 antisense phosphorothioate oligodeoxynucleotide (ASPODN) treatment group (IL-18 ASPODN group) and PLT+IL-18 SPODN treatment group (IL-18 SPODN group) in which liposomes encapsulated IL-18 ASPODN or IL-18 SPODN were intravenous injection every day after PLT. BrdU labeling of hepatocytes, expression of IL-18 protein and IFN-gamma mRNA in liver graft, and serum level of IFN-gamma were measured with immunohistochemistry analysis, Western blotting, semi-quantification RT-PCR, and ELISA, respectively.</p><p><b>RESULTS</b>Although regeneration of liver graft from each group peaked 72 hour after transplantation, BrdU labeling of hepatocytes in IL-18 ASPODN group (58.3%+/-7.5%) were significantly higher than those of PLT group (31.6%+/-6.7%) (t=6.503, P<0.001) and IL-18 SPODN group (33.4%+/-5.5%) (t=6.558, P<0.001). Expression of IL-18 protein and IFN-gamma mRNA in liver graft, and serum level of IFN-gamma in IL-18 ASPODN group from 48 hour, 72 hour and 96 hour after transplantation were significantly suppressed compared with PLT group (IL-18protein t=2.950, t=5.916, t=7.947, P<0.05, P<0.001; INF-gamma mRNA t=2.558, t=6.292, t=8.925, P<0.05, P<0.001; IFN-gamma level t=16.998, t=15.483, t=54.723, P<0.001) and IL-18 SPODN group (IL-18 protein t=2.845, t=6.062, t=6.973, P<0.05, P<0.001; INF-gamma mRNA t=3.117, t=6.154, t=8.738, P<0.05, P<0.001; IFN-gamma level t=14.531, t=18.139, t=46.924, P<0.001).</p><p><b>CONCLUSION</b>IL-18 ASPODN could promote hepatocyte regeneration of allogeneic partial liver graft by the suppression of IL-18 and IFN-gamma production.</p>