Emodin alleviates LPS-induced myocardial injury through inhibition of NLRP3 inflammasome activation
Emodin alleviates LPS-induced myocardial injury through inhibition of NLRP3 inflammasome activation
复制标题
大黄素通过抑制NLRP3炎性体激活减轻LPS诱导的心肌损伤
DOI：
10.1002/ptr.7191
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发表时间：
2021-06-16
影响因子：
7.2
通讯作者：
Lu, Zhongqiu
中科院分区：
文献类型：
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作者：
Dai, Shanshan;Ye, Bozhi;Lu, Zhongqiu
心肌损伤和心血管功能障碍是脓毒症的严重后果，并导致高死亡率。目前，脓毒症心肌损伤的发病机制尚不清楚，治疗手段有限。本研究旨在探讨大黄素对脓毒性心肌损伤的保护作用及其机制。分别使用脂多糖（LPS）诱导的C57 BL/6小鼠和心肌细胞作为体内和体外脓毒症模型。结果表明，大黄素可减轻LPS诱导的脓毒症小鼠的心功能不全，心肌损伤，提高存活率。大黄素可降低LPS诱导的炎症细胞因子水平和心肌炎症反应。大黄素降低了LPS诱导的脓毒症小鼠心脏组织中NOD样受体蛋白3（NLRP 3）和Gasdermin D（GSDMD）的表达。在体外，大黄素通过抑制NLRP 3炎性小体激活减轻LPS诱导的心肌细胞损伤和炎症。此外，NLRP 3抑制剂用于进一步证实NLRP 3炎性体在LPS诱导的心肌损伤中的功能。综上所述，我们的研究结果表明，大黄素通过减轻炎症反应和抑制NLRP 3炎性体激活的心肌细胞焦亡来改善LPS诱导的心肌损伤和心功能不全，这为预防和治疗脓毒症心肌损伤提供了可行的策略。
Myocardial injury and cardiovascular dysfunction are serious consequences of sepsis and contribute to high mortality. Currently, the pathogenesis of myocardial injury in sepsis is still unclear, and therapeutic approaches are limited. In this study, we investigated the protective effect of emodin on septic myocardial injury and the underlying mechanism. Lipopolysaccharide (LPS)‐induced C57BL/6 mice and cardiomyocytes were used as models of sepsis in vivo and in vitro, respectively. The results showed that emodin alleviated cardiac dysfunction, myocardial injury and improved survival rate in LPS‐induced septic mice. Emodin attenuated the levels of inflammatory cytokines and cardiac inflammation induced by LPS. Emodin reduced NOD‐like receptor protein 3 (NLRP3) and Gasdermin D (GSDMD) expression in the heart tissue of LPS‐induced septic mice. In vitro, emodin alleviated LPS‐induced cell injury and inflammation in cardiomyocytes by inhibiting NLRP3 inflammasome activation. In addition, an NLRP3 inhibitor was used to further confirm the function of the NLRP3 inflammasome in LPS‐induced myocardial injury. Taken together, our findings suggest that emodin improves LPS‐induced myocardial injury and cardiac dysfunction by alleviating the inflammatory response and cardiomyocyte pyroptosis by inhibiting NLRP3 inflammasome activation, which provides a feasible strategy for preventing and treating myocardial injury in sepsis.