Jin Yuzi, Fleishman Joshua S, Ma Yudong, Jing Xiaoqing, Guo Qin, Shang Weiguang, Wang Hongquan
Department of Pediatrics, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110020, People's Republic of China.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.
Drug Des Devel Ther. 2025 Feb 14;19:1025-1041. doi: 10.2147/DDDT.S506537. eCollection 2025.
Cardiac or myocardial dysfunction induced by sepsis, known as sepsis-induced cardiomyopathy or sepsis-induced myocardial injury (SIMI), is a common complication of sepsis and is associated with poor outcomes. However, the pathogenesis and molecular mechanisms underlying SIMI remain poorly understood, requiring further investigations. Emerging evidence has shown that NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasomes contribute to SIMI. Compounds that inhibit NLRP3-associated pyroptosis may exert therapeutic effects against SIMI. In this review, we first outlined the principal elements of the NLRP3 signaling cascade and summarized the recent studies highlighting how NLRP3 activation contributes to the pathogenesis of SIMI. We outlined selective small-molecule modulators that function as NLRP3 inhibitors and delineated their mechanisms of action to attenuate SIMI. Finally, we discuss the major limitations of the current therapeutic paradigm and propose possible strategies to overcome them. This review highlights the pharmacological inhibition of SIMI as a promising therapeutic strategy.
脓毒症诱发的心脏或心肌功能障碍，称为脓毒症诱发的心肌病或脓毒症诱发的心肌损伤（SIMI），是脓毒症的常见并发症，且与不良预后相关。然而，SIMI的发病机制和分子机制仍知之甚少，需要进一步研究。新出现的证据表明，含核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎性小体与SIMI有关。抑制NLRP3相关细胞焦亡的化合物可能对SIMI具有治疗作用。在本综述中，我们首先概述了NLRP3信号级联的主要成分，并总结了最近的研究，这些研究强调了NLRP3激活如何促成SIMI的发病机制。我们概述了作为NLRP3抑制剂起作用的选择性小分子调节剂，并描述了它们减轻SIMI的作用机制。最后，我们讨论了当前治疗模式的主要局限性，并提出了克服这些局限性的可能策略。本综述强调，对SIMI进行药理学抑制是一种有前景的治疗策略。
