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Experimental Study On Intrahepatic Stem/Progenitor Cells Involved In ALPPS 1 Postoperative Liver Regeneration

Posted on:2019-01-27Degree:MasterType:Thesis
Country:ChinaCandidate:M HuangFull Text:PDF
GTID:2334330545489325Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective: Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is a novel liver resection technique,which can stimulate the fast regeneration of remnant liver within a short time.However,the exact mechanism of such liver restoration remains unclear.This article aims to establish a stable animal model of Associating liver partition and portal vein ligation for staged hepatectomy and to explore whether intrahepatic stem /progenitor cells participate in the regeneration of liver after ALPPS.Methods:72 male Sprague-Dawley(SD)were randomly assigned to three experimental groups(n=24)and correspondingly received ALPPS,PVL and Sham operation.The hepatic regeneration rate(HRR),Ki-67 staining,liver biochemical parameters(AST?ALT?TBIL)and histopathology were assessed at 24 h,48h,72 h and 7 days after the operation.The rat intrahepatic stem / progenitor cell(oval cells,OCs)specific marker OV-6 was examined by Immunohistochemistry,Immunofluorescence and Western blot.Meanwhile,cytokines such as IL-6?TNF-a and HGF in the plasma were investigated by ELISA respectively.Results: The liver regeneration rate(HRR)of ALPPS group was significantly higher than that of PVL group on the 3 and 7 days after operation(p<0.05).At the same time,the liver regeneration rate of ALPPS group and PVL group was higher than that of Sham group after surgical at each points.(p<0.05).Compared with PVL group,the rate of Ki-67 positive cells in ALPPS group were significantly higher than those in PVL group on the 2 and 3days after surgery(P<0.05).And Ki-67 positive cells ratio in ALPPS group and PVL group were significantly higher than that of Sham group after surgical at2d?3d and 7days(P <0.05).The levels of AST and ALT in PVL and ALPPS groups increased significantly and reached the peak on the one day after postoperative,meanwhile,the ALPPS group were significantly higher than those in PVL group at early of postoperative;Immunohistochemistry results show:the expression of OV-6 positive cells ratio in ALPPS group was significantly higher than that in PVL group at the 1d and 2d after operation(P<0.05),And ALPPS group and PVL group were higher than Sham group at all time points(p<0.05).Meanwhile,the results of immunofluorescence also showed that the expression of OV-6 positive cells ratio in ALPPS group was higher than that of in PVL group(P<0.05),ALPPS group and PVL group were higher than Sham group at each time point(p <0.05).The western blot revealed that the OV-6 expression level was higher in ALPPS group than in the PVL group at 1d and 2d after surgery(p<0.05),but,there was no significant difference in OV-6 protein expression between ALPPS group and PVL group at3 d and 7 days after surgery.The levels of IL-6,TNF-?and HGF in the ALPPS group were significantly higher than those in the PVL group on the 1d and 2d(p<0.05).conclusion:The results of HRR,Ki-67 positive expression and Liver function indicators showed that ALPPS induced liver regeneration was superior to PVL,and intrahepatic stem / progenitor cells may be involved in the rapid liver regeneration,and the possible mechanism is that ALPPS cause relatively severe liver damage,which stimulates a high level of inflammation in the body that further activate mobilization and activation of intrahepatic stem/progenitor cells and thus participate in rapid liver hyperplasia recovery.
Keywords/Search Tags:ALPPS, Portal Vein Ligation, Liver Regeneration, Liver Stem Cells, Oval Cells
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