Exogenous SDF-1α delivery combined with EPCs transplantation produces a superior protective effect on hepatic ischemia reperfusion injuryed rats

Abstract:

Objective：To investigate the effects of exogenous SDF-1αdelivery or EPCs transplantation or SDF-1αcombined with EPCs transplantation on hepatic ischemia reperfusion injuryed rats. Methods：EPCs were extracted from bone marrow of LEWIS rats and cultured for days for phenotype identification with flow cytometry and functional identification with confocal laser. The orthotopic liver transplantation models were established in mice，which were divided randomly into five groups：A group，sham group；B group，surgery group；C group，SDF-1α group；D group，EPCs group；E group，SDF-1α+EPCs group. The rats were euthanased after 12 h reperfusion，and the liver tissues in each group were assayed with immunohistochemistry for liver regeneration and HGF ex－pression. The protein levels of VEGF，HGF，TGF-β，Bcl-2 and Caspase-3 in each group were assayed with Western blot，and the expression of VEGF，HGF and TGF-β in liver homogenates with ELISA. Results：The CD34 and CD133 positive rates of EPCs extracted from LEWIS rats were 78.32% and 70.76 respectively，and the binding capacity of ac-LDL and UEA-1 in EPCs accounted for over 80%. The number of EPCs（79.6±6.3） induced by SDF-1αwas significant higher than that in control group（36.2±2.9）（P=0.000）. In liver tissues of each group，the immunohistochemical scores in C and D groups of HGF secretion and liver regeneration were significantly higher than those in A and B groups（P=0.000），and the immunohistochemical scores in E group was significant higher than those in C and D groups（P=0.000）. The results of proteins ex－pression showed that the expressions of VEGF，HGF，TGF-β and Bcl-2 proteins were higher in C and D groups than in A and B groups（P=0.000）；the expressions of VEGF，HGF and TGF-β proteins were significantly higher in E group than in C and D groups（P=0.000），but there was no significant difference in Bcl-2 expression among C，D，E groups. The expressions of Caspase-3 protein were significantly higher in B，C，D groups than in A group（P=0.000），but the expression of Caspase-3 was significant lower in E group than in C and D groups（P=0.000）. The ELISA got the same results. Conclusion：Exogenous SDF-1α delivery combined with EPCs transplantation produces a superior protective effect on hepatic ischemia reperfusion injuryed rats，which could induce the re－generation of liver and reduce hepatocyte apoptosis.