Transplant international : official journal of the European Society for Organ Transplantation

Necrostatin-1 inhibits Hmgb1-IL-23/IL-17 pathway and attenuates cardiac ischemia reperfusion injury.

PMID 24810904


Ischemia reperfusion (IR) injury is a major issue in cardiac transplantation and inflammatory processes play a major role in myocardial IR injury. Necrostatin-1 (Nec-1) is a small molecule capable of inhibiting RIP1 kinase activity and attenuates inflammation-mediated tissue injury. In our study, hearts of C57Bl/6 mice were flushed and stored in cold Bretschneider solution for 8xa0h and then transplanted into syngeneic recipients. We found that Nec-1 decreased cardiomyocyte necrosis and recruitment of neutrophils and macrophages. Troponin T (TnT) production on 24xa0h after myocardial IR injury was reduced by Nec-1 administration. Cardiac output at 60xa0mmHg of afterload pressure was significantly increased in hearts with Nec-1 administration and the cardiac allograft survival in Nec-1-treated animals was significantly prolonged (MSTxa0=xa090xa0days in IRxa0+xa0Nec-1 group, Pxa0