While ischemia itself can kill heart muscle, much of the infarction after a transient period of coronary artery occlusion has been found to result from injury during reperfusion. Here we review the role of inflammation and possible pyroptosis in myocardial reperfusion injury. Current evidence suggests pyroptosis’s contribution to infarction may be considerable. Pyroptosis occurs when inflammasomes activate caspases that in turn cleave off an N-terminal fragment of gasdermin D. This active fragment makes large pores in the cell membrane thus killing the cell. Inhibition of inflammation enhances cardiac tolerance to ischemia and reperfusion injury. Stimulation of the purinergic P2X7 receptor and the β-adrenergic receptor and activation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) by toll-like receptor (TLR) agonists are all known to contribute to ischemia/reperfusion (I/R) cardiac injury through inflammation, potentially by pyroptosis. In contrast, stimulation of the cannabinoid CB2 receptor reduces I/R cardiac injury and inhibits this pathway. MicroRNAs, Akt, the phosphate and tension homology deleted on chromosome 10 protein (PTEN), pyruvate dehydrogenase and sirtuin-1 reportedly modulate inflammation in cardiomyocytes during I/R. Cryopyrin and caspase-1/4 inhibitors are reported to increase cardiac tolerance to ischemic and reperfusion cardiac injury, presumably by suppressing inflammasome-dependent inflammation. The ambiguity surrounding the role of pyroptosis in reperfusion injury arises because caspase-1 also activates cytotoxic interleukins and proteolytically degrades a surprisingly large number of cytosolic enzymes in addition to activating gasdermin D.

虽然缺血本身可以杀死心肌，但已发现在短暂的冠状动脉闭塞后的大部分梗塞是由再灌注期间的损伤引起的。在这里，我们回顾了炎症和可能的细胞焦亡在心肌再灌注损伤中的作用。目前的证据表明细胞焦亡对梗死的影响可能相当大。当炎症小体激活半胱天冬酶时，就会发生焦亡，半胱天冬酶又会切割掉 gasdermin D 的 N 端片段。这个活性片段会在细胞膜上形成大孔，从而杀死细胞。抑制炎症可增强心脏对缺血和再灌注损伤的耐受性。Toll 样受体 (TLR) 激动剂对嘌呤能 P2X7 受体和 β-肾上腺素能受体的刺激以及活化 B 细胞 (NF-κB) 的核因子 κ-轻链增强子的激活均已知会导致缺血/炎症引起的再灌注 (I/R) 心脏损伤，可能是细胞焦亡。相比之下，大麻素 CB2 受体的刺激可减少 I/R 心脏损伤并抑制该途径。据报道，MicroRNA、Akt、10 号染色体蛋白 (PTEN) 上缺失的磷酸盐和张力同源性、丙酮酸脱氢酶和 sirtuin-1 在 I/R 期间调节心肌细胞的炎症。据报道，Cryopyrin 和 caspase-1/4 抑制剂可增加心脏对缺血和再灌注心脏损伤的耐受性，可能是通过抑制炎症小体依赖性炎症。