Beta-Asarone Alleviates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammatory Response and NLRP3 Inflammasome Mediated Pyroptosis

摘要

Beta-asarone (beta-Asarone), the major component of Acorns tatarinowii Rhizoma, has been proved to be muti-pharmacological activities including anti-inflammation, and which is effective in protecting the central nervous system. However, the effect of beta-Asarone on myocardial ischemia-reperfusion (I/R) injury is not yet clear. This study used a rat model with 45min occlusion and 24h releasing of proximal segment of left anterior descending coronary artery. The effects of beta-Asarone on cardiac histopathology, myocardial infarction size, levels of cardiac troponin T (cTNT), myeloperoxidase (MPO) and interleukin-1 beta (IL-1 beta), protein expressions of apoptosis-associated speck-like protein containing a CARD (ASC), Nod-like receptor protein 3 (NLRP3), caspase-1 and Gasdermin D (GSDMSD), and left ventricular performance were studied respectively. Our results showed that administration of beta-Asarone significantly improved the heart outcome after myocardial ischemia and reperfusion in terms of less infarction size and lower serum cTNT concentration. Further, beta-Asarone treatment evidently inhibited inflammatory response with less granulocyte infiltration, mild tissue edema and lower tissue MPO content, it also suppressed NLRP3 signal pathway and cardiac cell's pyroptosis for less protein expressions of ASC and NLRP3, lower level cleavage activation of caspase-1 and GSDMSD, and lower serum IL-1 beta concentration. Finally, beta-Asarone treatment well preserved the left ventricular performance with higher ejection fraction and fractional shortening. The experimental results suggested that beta-Asarone was protective against myocardial ischemia-reperfusion injury, in which inhibition of inflammatory response and suppression of NLRP3 inflammasome mediated pyroptosis were supposed to play a vital role.