rock1 inhibitor abrogates chronic rejection in rat cardiac model systemrock1抑制剂废除慢性排斥反应在大鼠心脏模型系统.pdf

Open Journal of Organ Transplant Surgery, 2012, 2, 46-51 /10.4236/ojots.2012.24012 Published Online November 2012 (http://www.SciRP.org/journal/ojots) ROCK1 Inhibitor Abrogates Chronic Rejection in Rat Cardiac Model System 1,2,3 1,2* 1,2 1,2 4 Li Zhang , Malgorzata Kloc , Neelam Tejpal , Junping You , Andrea M. Cordero-Reyes , Keith A. Youker4, Rafik M. Ghobrial1,2* 1Department of Surgery, The Methodist Hospital, Houston, USA 2The Methodist Hospital Research Institute, Houston, USA 3The Department of Transplantation, The First Central Clinical College of Tianjin Medical University, Tianjin, China 4The Methodist DeBakey Heart Vascular Center, Houston, USA * * Email: mkloc@, RMGhobrial@ Received September 20, 2012; revised October 29, 2012; accepted November 8, 2012 ABSTRACT Background: We have shown previously that the abrogation of acute and chronic rejection of rat cardiac allografts oc- curs through the down-regulation of RhoA pathway and involves the changes in RhoA kinase (ROCK)-dependent actin cytoskeleton and T cell motility. Here we studied the ability of the Y-27632, a highly selective inhibitor of Rho-associated protein kinase p160ROCK (ROCK1), to abrogate chronic rejection of the allograft and influence T cell infiltration. Methods: Heterotopic cardiac transplants were performed between donor Wistar Furth (WF) and ACI re- cipient rats. Controls received sub-therapeutic d