Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Clinical College of Wuhan University, No.158 Wuyang Avenue, Enshi, 445000, Hubei, China.
Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Naunyn Schmiedebergs Arch Pharmacol. 2023 Jul;396(7):1461-1470. doi: 10.1007/s00210-023-02409-5. Epub 2023 Feb 7.
Dilated cardiomyopathy (DCM) is the major cause of heart failure and has a poor prognosis. The accumulating evidence points to an essential role of the inflammatory component in the process of DCM. Inhibitors of sodium-glucose cotransporter 2 (SGLT2) are widely used to treat heart failure patients due to their cardiac benefits. However, their role in DCM remains unclear. We used the doxorubicin (Dox)-induced DCM model for our study. The SGLT2 inhibitor dapagliflozin (Dapa) improved cardiac function in mice treated with doxorubicin and attenuated the activation of the nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome pathway and the expression of inflammatory factors. In addition, dapagliflozin suppresses NLRP3 activation by decreasing p38-dependent toll-like receptor 4 (TLR4) expression. In our study, dagliflozin improves cardiac function in DCM by inhibiting the activity of the NLRP3 inflammasome.
扩张型心肌病（DCM）是心力衰竭的主要原因，预后不良。越来越多的证据表明炎症成分在 DCM 过程中起着重要作用。钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂由于其对心脏的益处而被广泛用于治疗心力衰竭患者。然而，它们在 DCM 中的作用尚不清楚。我们使用阿霉素（Dox）诱导的 DCM 模型进行了研究。SGLT2 抑制剂达格列净（Dapa）改善了 doxorubicin 治疗小鼠的心脏功能，并减弱了核苷酸结合寡聚结构域样受体家族蛋白 3（NLRP3）炎性小体途径的激活和炎症因子的表达。此外，达格列净通过降低 p38 依赖性 Toll 样受体 4（TLR4）表达来抑制 NLRP3 的激活。在我们的研究中，达格列净通过抑制 NLRP3 炎性小体的活性来改善 DCM 中的心脏功能。
