Aims

The purpose of this study was to investigate the protective effects of puerarin and elucidate the underlying mechanisms of puerarin in myocardial ischemia/reperfusion (MI/R) injury.

Main methods

C57BL/6 mice were exposed to puerarin (100 mg/kg) with or without the SIRT1 inhibitor nicotinamide (500 mg/kg) and then subjected to MI/R operation. Myocardial infarct size, serum creatine kinase-MB (CK-MB) activity, apoptotic cell death, and cardiac structure and function were examined to evaluate MI/R injury. RT-PCR and western blotting were used to determine the inflammatory response and inflammasome activation, as well as activation of SIRT1/NF-κB pathway.

Results

Puerarin significantly reduced myocardial infarct size, serum CK-MB activity, and apoptotic cell death, and improved cardiac structural damage and dysfunction. Moreover, puerarin notably decreased the mRNA and protein levels of TNF-α, IL-6, and IL-1β, indicating that puerarin attenuated MI/R-induced inflammation. Furthermore, puerarin markedly decreased the protein levels of Ac-NF-κB, NLRP3, cleaved caspase-1, cleaved IL-1β, and cleaved IL-18 and increased the protein level of SIRT1. More importantly, the SIRT1 inhibitor nicotinamide prevented these puerarin-induced cardioprotective effects and regulation of the SIRT1/NF-κB pathway, as well as the NLRP3 inflammasome activation.

Conclusion

Puerarin protected against MI/R injury by inhibiting inflammatory responses probably via the SIRT1/NF-κB pathway, and inhibition of the NLRP3 inflammasome was also involved in puerarin-induced cardioprotective effects. These results suggest that puerarin may be a novel candidate for the treatment of ischemic heart disease.

中文翻译：

---

葛根素通过抑制炎症和NLRP3炎性体保护心肌缺血/再灌注损伤：SIRT1 /NF-κB途径的作用

目的

这项研究的目的是调查葛根素的保护作用，并阐明葛根素在心肌缺血/再灌注（MI / R）损伤中的潜在机制。

主要方法

将C57BL / 6小鼠暴露于有或没有SIRT1抑制剂烟酰胺（500 mg / kg）的葛根素（100 mg / kg）中，然后进行MI / R手术。检查心肌梗塞大小，血清肌酸激酶-MB（CK-MB）活性，凋亡细胞死亡以及心脏结构和功能，以评估MI / R损伤。RT-PCR和western blotting用于确定炎症反应和炎症小体激活以及SIRT1 /NF-κB途径的激活。

结果

葛根素可显着减少心肌梗塞面积，血清CK-MB活性和凋亡细胞死亡，并改善心脏结构损伤和功能障碍。此外，葛根素显着降低了TNF-α，IL-6和IL-1β的mRNA和蛋白水平，表明葛根素减轻了MI / R诱导的炎症。此外，葛根素显着降低了Ac-NF-κB，NLRP3，裂解的caspase-1，裂解的IL-1β和裂解的IL-18的蛋白水平，并提高了SIRT1的蛋白水平。更重要的是，SIRT1抑制剂烟酰胺阻止了葛根素诱导的心脏保护作用和对SIRT1 /NF-κB途径以及NLRP3炎性体激活的调节。

结论

葛根素通过抑制炎症反应（可能通过SIRT1 /NF-κB途径）来预防MI / R损伤，而葛根素诱导的心脏保护作用也涉及抑制NLRP3炎症小体。这些结果表明，葛根素可能是治疗缺血性心脏病的新型候选药物。