Calcium dysregulation and mitochondrial dysfunction are key elements in the development of sepsis-induced cardiac dysfunction. Evidences have suggested that inhibition of Wnt/β-Catenin signalling prevents cardiac dysfunction and remodelling in surgical, hypertension and pressure overload models. The present study investigated the effects of Wnt/β-Catenin inhibitor on calcium overload and mitochondrial dysfunction in rat sepsis model of cardiomyopathy. Induction of sepsis by cecal ligation puncture (CLP) resulted in the up-regulation of cardiac β-catenin transcriptional levels and cardiac dysfunction depicted by increased serum lactate dehydrogenase, CK-MB levels reduced maximum (dp/dt max.) and minimum developed pressure (dp/dt min.), increased LVEsDP and relaxation constant tau values. Moreover, oxidative and inflammatory stress, immune cell infiltration, increased myeloperoxidase activity, enhanced caspase-3 activity and fibronectin protein levels were observed in septic rat’s heart. Also, septic rat’s heart displayed mitochondrial dysfunction due to mPTP opening, increased calcium up-regulation in left ventricular apex tissues and whole heart, increased collagen staining, necrosis and structural damage. Pre-treatment with Wnt/β-Catenin antagonist attenuated sepsis-induced serum and tissue biochemical changes, cardiac dysfunction and structural alterations by inhibiting mitochondrial mPTP opening and restricting calcium overloading in cardiac tissue.

钙失调和线粒体功能障碍是脓毒症引起的心脏功能障碍发展的关键因素。有证据表明，抑制 Wnt/β-Catenin 信号传导可预防手术、高血压和压力超负荷模型中的心脏功能障碍和重塑。本研究探讨了 Wnt/β-Catenin 抑制剂对脓毒症心肌病模型大鼠钙超载和线粒体功能障碍的影响。盲肠结扎穿刺 (CLP) 诱导脓毒症导致心脏 β-连环蛋白转录水平上调，并通过血清乳酸脱氢酶增加、CK-MB 水平降低最大 (d p /d t max.) 和最小程度来描述心功能障碍产生的压力 (d p /d t min.)、增加的 LVEsDP 和松弛常数 tau 值。此外，在脓毒症大鼠的心脏中观察到氧化和炎症应激、免疫细胞浸润、髓过氧化物酶活性增加、caspase-3活性和纤连蛋白水平增强。此外，脓毒症大鼠的心脏由于 mPTP 打开而表现出线粒体功能障碍，左心室心尖组织和整个心脏中的钙上调增加，胶原染色、坏死和结构损伤增加。 Wnt/β-连环蛋白拮抗剂预处理通过抑制线粒体 mPTP 打开和限制心脏组织中的钙超载，减轻脓毒症引起的血清和组织生化变化、心脏功能障碍和结构改变。