Postconditioning with a CpG containing Oligodeoxynucleotide ameliorates myocardial infarction in a murine closed-chest model

作者：Kim, Se-Chan^*; Wu, Shuijing; Fang, Xiangming; Neumann, Jens; Eichhorn, Lars; Schleifer, Grigorij; Boehm, Olaf; Meyer, Rainer; Frede, Stilla; Hoeft, Andreas; Baumgarten, Georg; Knuefermann, Pascal

来源：Life Sciences, 2014, 119(1-2): 1-8.

DOI：10.1016/j.lfs.2014.09.029

• postconditioning
• Toll-like receptor
• myocardial infarction
• innate immunity
• cytokines

Aims: Toll-like receptor (TLR)9 ligand CpG-oligodeoxynucleotide (CpG-ODN) exerts preconditioning in myocardial ischemia/reperfusion. We hypothesized a postconditioning effect of CpG-ODN in a murine closed-chest model of myocardial infarction. @@@ Materials and Methods: C57BL/6 (12 weeks, male, WT) mice were instrumented at the left anterior descending artery, then allowed 5d of recovery before 30 min ischemia. Treatments comprised: 1) PBS: 250 mu l phosphate buffer solution intraperitoneally 5 min before reperfusion and 2) IPC (ischemic postconditioning): 3 twenty-second reperfusion and occlusion episodes at the end of ischemia 3) CpG-ODN: 1668 thioate 0.2 mu mol/kg BW intraperitoneally 5 min before reperfusion. Infarct size was assessed via triphenyltetrazolium chloride (TTC) staining after 2 and 24 h reperfusion. Myocardial mRNA-expression of cytokines was measured using real-time PCR after 2 h reperfusion. Phosphatidylinosito1-3 kinase (PI3K)-inhibitor wortmannin was injected intraperitoneally in WC 15 min before postconditioning and PBS in each group. Cardiac function in WT was assessed with a left-ventricular pressure-volume catheter at 24 h reperfusion. @@@ Key findings: Following 30 min ischemia and 2 h reperfusion, infarct size was diminished by 90% in WT postconditioned with CpG-ODN (2.4 +/- 1.55 IS/AAR%) and IPC (1.98 +/- 1.03 IS/AAR%) compared to PBS mice (23.2 +/- 3.97 IS/AAR%). Infarct size increased following 24 h reperfusion but the differences remained robust. Expression of TNF-alpha and IL-10 was increased in CpG-ODN. Wortmannin abolished the postconditioning effect of CpG-ODN and IPC. Ejection fraction and preload-recruitable stroke work were significantly greater in CpG-ODN mice. @@@ Significance: CpG-ODN confers postconditioning via activation of TLR9. Cardiac function is preserved following CpG-ODN postconditioning. The PI3K -inhibitor wortmannin attenuates CpG-ODN postconditioning.

• 出版日期2014-12-5
• 单位浙江大学