| Objiective: Based on the establishment of ALPPS rat model,a preliminary study on the mechanism of ALPPS to promote the rapid growth of liver was carried out.Whether future liver is the true significance of regeneration and the effect of ALPPS on liver function.Methods: 60 male SD rats weighting 200~250g were randomly divided into four groups(n = 15 in each group).It is Associating Liver Partition and Portal vein ligation for Staged hepatectomy(ALPPS)group,Portal vein ligation(PVL)group,in situ splitting(ISS)group and sham-operation(sham)group.The following items were monitored:First,the future liver remnant generation rate after 3d,7d and 10 d.Second,canges of liver function after 3d,7d and 10 d.Third,serum levels of hepatocyte growth factor(HGF),tumor necrosis factor alpha(tnf-?),and interleukin 6(IL-6)after 3d ? 7d and 10 d.Fourth,the liver morphological and pathological changes after 3d?7d and 10 d.Results: 1.The rat model of left lateral lobe reserved ALPPS was successfully established.2.After operation,the survival rate of ALPPS group was 87%,the survival rate of PVL group was higher than that of group,and the survival rate of ISS group and Sham group was 100%.3.After 3d,7d and 10 d,the regeneration rate of FLR were(47.55±3.69)%,(69.53±2.35)%,(76.92±5.21)% in ALPPS group;the regeneration rate of FLR were(15.38±3.24)%,(26.83±2.18)%,(38.20±4.12)% in PVL group;the regeneration rate of FLR were(1.05±0.42)%,(2.73±1.56)%,(8.21±1.59)% in PVL group;the regeneration rate of FLR were(0.68±0.26)%,(2.53±0.52)%,(5.37±1.15)% in PVL group.Obviously,FLR regeneration rate of ALPPS group was significantly higher than the other three groups,the difference was statistically significant(P<0.01).4.The serum ALT and AST levels of ALPPS group,PVL group,ISS group and Sham group at each time point were as follows:First,the serum ALT levels after 3d were 274.80±37.13U/L,217.60±61.91U/L,172.20±48.90U/L,38.80±21.02U/L;the serum AST levels after 3d were 540.20±80.81 U/L,362.20±46.74U/L,371.20±47.07 U/L,44.80±33.97 U/L.Second,the serum ALT levels after 7d were 81.20±54.85 U/L,76.40±53.89 U/L,54.40±39.60 U/L,21.20±9.36 U/L;the serum AST levels after 7d were 100.20±68.09 U/L,39.80±45.24 U/L,72.40±51.41 U/L,22.60±9.63 U/L.Third,the serum ALT levels after 10 d were 16.40±2.70 U/L,14.20±5.81U/L,17.80±9.20 U/L,13.60±5.94U/L;the serum AST levels after 10 d were 25.60±5.68 U/L,17.40±5.23U/L,17.20±2.95U/L,22.20±6.21U/L.Obviously,the serum ALT and AST levels of ALPPS group,PVL group and ISS group were significantly increased.The serum ALT and AST levels of the three groups were gradually reduced after 7d,and returned to normal after 10 d.The serum ALT and AST levels of Sham group have no obvious change after 3d,7dand 10 d.The ALT and AST levels of ALPPS group after 3d were significantly higher than those in PVL group and ISS group.The difference was statistically significant(P<0.01).5.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression of HGF,TNF-and IL-6 in serum of ALPPS group,ISS group,PVL group,and then gradually decreased after 3d,and gradually returned to normal after 7d.The serum HGF,TNF-? and IL-6 of ALPPS group after 3d were 0.75±0.04ng/ml,85.63±15.32ng/ml,132.25±25.72ng/ml.The serum HGF,TNF-? and IL-6 of PVL group after 3d were 0.68±0.02ng/ml,51.20±5.14ng/ml,78.20±8.23ng/ml.The serum HGF,TNF-? and IL-6 of PVL group after 3d were 0.70±0.03ng/ml,63.71±8.35ng/ml,93.21±10.95ng/ml.The serum HGF,TNF-? and IL-6 of PVL group after 3d were0.53±0.02ng/ml,21.02±1.38ng/ml,52.54±1.69ng/ml.The expression levels of HGF,TNF-and IL-6 in group ALPPS were significantly higher than those in the other three groups.The difference was statistically significant(P<0.05).6.In ALPPS group,there were a disorder of hepatic cord structure,liver multiple focal necrosis,hepatic steatosis,ballooning degeneration and edema,after 3d.In PVL group,there were perisinusoidal space narrowing and congestion,no structural disorder,swelling of the liver cells,ballooning degeneration after 3d.Compared with ALPPS group,the necrotic area was relatively small.After 7d,both of the groups liver cable structure,liver cell morphology,congestion and necrosis decreased.In ISS Group and sham group,the morphology and structure of liver cells were normal.Conclusion: 1.In this study,we successfully established a rat model of two hepatic resection combined with hepatic disconnection and portal vein ligation(ALPPS).2.The results showed that ALPPS could promote the rapid growth of remnant liver volume(FLR).Compared with portal vein ligation(PVL),it was more significant.It is proved by pathology that liver regeneration is true.3.ALPPS may promote liver regeneration mechanism of portal vein shunt and liver parenchyma caused by traumatic reaction induced by cytokines(such as HGF,TNFalpha,IL-6)related to high expression.4.After ALPPS,the liver function damage of rats was obvious.It was the most significant after 3d,and the gradually returned to normal after 7d-10 d. |
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