钠-葡萄糖协同转运蛋白 2 抑制剂卡格列净可改善实验性自身免疫性心肌炎中的心脏炎症。
SGLT2 inhibitor, canagliflozin, ameliorates cardiac inflammation in experimental autoimmune myocarditis.
机构信息
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
出版信息
Int Immunopharmacol. 2022 Sep;110:109024. doi: 10.1016/j.intimp.2022.109024. Epub 2022 Jul 13.
Myocarditis is an inflammatory cardiovascular disease which contributes to dilated cardiomyopathy (DCM) and heart failure. Canagliflozin (CANA) exerts anti-inflammatory and cardioprotective effects in heart failure besides its hypoglycemic effect. However, the role of CANA in myocarditis has not been elucidated. In this work, CANA treatment markedly alleviated cardiac inflammation and improved cardiac function in experimental autoimmune myocarditis (EAM) mice induced by α-myosin-heavy chain peptides. The expressions of NLRP3 inflammasome complexes (NLRP3, ASC, and Caspase-1) and their downstream molecules (IL-1β, IL-18) were significantly downregulated by CANA, accompanied with reduced Th17 cell infiltration in hearts. Furthermore, Bax/Bcl-2 ratio, Cleaved Caspase-3 protein level and the percentage of TUNEL-positive myocardial cells, which usually indicated apoptosis, were reduced by CANA treatment. These findings suggest CANA could be a valuable medication for myocarditis treatment.
心肌炎是一种炎症性心血管疾病，可导致扩张型心肌病（DCM）和心力衰竭。卡格列净（CANA）除了具有降血糖作用外，还具有抗炎和心脏保护作用。然而，CANA 在心肌炎中的作用尚未阐明。在这项工作中，CANA 治疗显著减轻了由α-肌球蛋白重链肽诱导的实验性自身免疫性心肌炎（EAM）小鼠的心脏炎症并改善了心脏功能。CANA 显著下调 NLRP3 炎性小体复合物（NLRP3、ASC 和 Caspase-1）及其下游分子（IL-1β、IL-18）的表达，同时减少心脏中 Th17 细胞的浸润。此外，CANA 治疗还降低了 Bax/Bcl-2 比值、Cleaved Caspase-3 蛋白水平和 TUNEL 阳性心肌细胞的百分比，这通常表明细胞凋亡减少。这些发现表明 CANA 可能是治疗心肌炎的一种有价值的药物。
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