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Necrostatin-1 Inhibits Hmgb1-IL-23/IL-17 Pathway and Attenuates Cardiac Ischemia Reperfusion Injury.
MedLine Citation:
PMID:  24810904     Owner:  NLM     Status:  Publisher    
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 8 hours 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 24h after myocardial IR injury was reduced by Nec-1 administration. Cardiac output at 60 mmHg 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 (MST = 90 days in IR + Nec-1 group, P < 0.05 as compared with IR group, MST = 83.5 days). Nec-1 treatment attenuated ROS generation and increased expression of NOS2 and COX-2. The expression of Hmgb1, IL-23 and IL-17A were also decreased with Nec-1 administration. Furthermore, the decreased TnT expression induced by Nec-1 was abrogated with exogenous Hmgb1 administration. In conclusion, Nec-1 played a protective role in cardiomyocyte IR injury and this was associated with inhibited Hmgb1-IL-23/IL-17 pathway. This article is protected by copyright. All rights reserved.
Anbin Zhang; Xiaogang Mao; Lin Li; Yunjie Tong; Yanli Huang; Yanli Lan; Hong Jiang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-8
Journal Detail:
Title:  Transplant international : official journal of the European Society for Organ Transplantation     Volume:  -     ISSN:  1432-2277     ISO Abbreviation:  Transpl. Int.     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-5-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8908516     Medline TA:  Transpl Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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