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A12386 Necrostatin-1 stable variant suppress necroptosis in ischemic-reperfusion hearts

Objectives: To investigate the effects of Necrostatin-1 stable variant on myocardial necroptosis in experimental mice with ischemical reperfusion injury. Methods: Male FVB/N mice were divided randomly into 4 groups: I/R plus DMSO buffer group (n = 8), I/R plus low dose NEC-1 s group (0.6 mg/kg)(n = 8), I/R plus normal dose NEC-1 s group (3 mg/kg)(n = 8) and I/R plus high dose NEC-1 s group (6 mg/kg)(n = 8). The hearts were performed occlusion of the left anterior descending coronary artery 30 min followed by 24 h reperfusion and intraperitional injection with NEC-1 s or 0.002% DMSO as control in I/R plus DMSO group 30 min before operation. The myocardial infarction size (MI) were examined; protein expression of RIP1, RIP3 and MLKL were determined by Western blot analysis. The mice were prepared by Langendroff method through same grouping method. The myocardial necrosis were detected by PI staining and LDH level in the perfusion effluent Results: Compared with I/R plus Buffer group, the NEC-1 s N group and NEC-1 s H group presented decreased infarction size, LDH level and PI positive cells; improved cardiac function; down-regulated protein level of RIP1, RIP3 and MLKL Conclusion: NEC-1 s may inhibite RIPK1 and reduced myocardial necroptosis, thereby attenuate I/R injury in mice heart.