the cox-2pgi2 receptor axis plays an obligatory role in mediating the cardioprotection conferred by the late phase of ischemic preconditioningcox-2pgi2受体轴起着的作用在调节赋予的心脏保护缺血预处理的后期阶段.pdfVIP

The COX-2/PGI2 Receptor Axis Plays an Obligatory Role in Mediating the Cardioprotection Conferred by the Late Phase of Ischemic Preconditioning 1 2 1 1 1 1 Yiru Guo , Deepali Nivas Tukaye , Wen-Jian Wu , Xiaoping Zhu , Michael Book , Wei Tan , 1 1 3 1 1 Steven P. Jones , Gregg Rokosh , Shuh Narumiya , Qianhong Li , Roberto Bolli * 1 Institute of Molecular Cardiology, University of Louisville, Louisville, Kentucky, United States of America, 2 Department of Internal Medicine, University of Louisville, Louisville, Kentucky, United States of America, 3 Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, Japan Abstract Background: Pharmacologic studies with cyclooxygenase-2 (COX-2) inhibitors suggest that the late phase of ischemic preconditioning (PC) is mediated by COX-2. However, nonspecific effects of COX-2 inhibitors cannot be ruled out, and the selectivity of these inhibitors for COX-2 vs. COX-1 is only relative. Furthermore, the specific prostaglandin (PG) receptors responsible for the salubrious actions of COX-2-derived prostanoids remain unclear. Objective: To determine the role of COX-2 and prostacyclin receptor (IP) in late PC by gene deletion. Methods: COX-2 knockout (KO) mice (COX-22/ 2), prostacyclin receptor KO (IP 2/ 2) mice, and respective wildtype (WT, COX- 2+/+ and IP+/+) mice underwent sham surgery or PC with six 4-min coronary occlusion (O)/4-min R cycles 24 h before a 30- min O/24 h R. Results: There were no significant differences in infarct size (IS) between non-preconditioned (non-PC)