Prolonged rat liver allograft survival by in vivo targeting OX40-siRNA OX40-OX40L co-stimulatory cascade blockade
- VernacularTitle:靶向OX40基因的siRNA抑制大鼠肝脏移植排斥反应的研究
- Author:
Jushan WU
;
Renpin XIA
;
Shichun LU
;
Yi ZHANG
;
Jinli LOU
;
Ning LI
- Publication Type:Journal Article
- Keywords:
Liver transplantation;
Graft rejection;
OX40;
siRNA
- From:
Chinese Journal of General Surgery
2008;23(7):516-519
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of blockading OX40-OX40L co-stimulatory signaling on the survival time of liver allograft in rat.Methods siRNA-expression vectors were constructed to targeting OX40.3～5 minutes before DA to Lewis orthotopic liver transplantation was performed,5×109 pfu of targeting OX40 siRNA plasmid DNA were diluted in 5 ml of phosphate buffered saline(PBS)and inlected intravenously into recipient Lewis rat over a period of 10 seconds.Serum IL-2 and IFN-γ levels were assayed by ELISA,and mix lymphocyte response(MLR)were tested by 3H-thymidine.Results The survival time of recipients in siRNA treatment group(74.0±9.3)was significantly longer than that in control group[(7.3±0.5)days].In experiment group,the inflammatory cell infihration and liver tissue structure destruction were very slight.The concentration of serum IL-2 was much lower in siRNA treatment group[(46±8.4)pg/ml]than that in control group[(286.5±14.6)pg/ml].Meanwhile,the concentration of serum IFN-γ was much lower in siRNA treatment group [(202.7±14.6)pg/ml]than that in control group[(1682.7±87.9)pg/ml].Conclusion Administration of OX40-siRNA can blockade OX40-OX40L co-stimulatory signaling pathway.hence inhibit the rejection of liver allograft.
