Department of Emergency, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of General Practice, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Bioengineered. 2022 Mar;13(3):7134-7146. doi: 10.1080/21655979.2022.2047256.
Sepsis-induced myocardial dysfunction (SIMD) is associated with high morbidity and mortality rates; however, it lacks targeted therapies. Modulating cardiomyocyte autophagy maintains intracellular homeostasis during SIMD. Clemastine, a histamine receptor inhibitor, promotes autophagy and other effective biological functions. Nevertheless, the effect of clemastine on SIMD remains unclear. This study aimed to explore the underlying mechanism of clemastine in cardiomyocyte injury in cecum ligation and perforation (CLP)-induced rats and lipopolysaccharide (LPS)-stimulated H9c2 cells. Clemastine (10 mg/kg, 30 mg/kg, and 50 mg/kg) was intraperitoneally injected after 30 min of CLP surgery. Serum cTnI levels and the 7-day survival rate were evaluated. Echocardiograms and H&E staining were used to evaluate cardiac function and structure. TEM was used to detect the mitochondrial ultrastructure and autophagosomes. Clemastine significantly improved the survival rate and reduced cTnI production in serum. Clemastine ameliorated cellular apoptosis, improved mitochondrial ultrastructure both and , increased ATP content, decreased dynamin-related protein 1 (DRP1) expression, and decreased mitochondrial ROS levels. Additionally, clemastine treatment increased autophagosome concentration, LC3II/LC3I rate, and Beclin 1 expression. However, 3-methyladenine (3-MA), an autophagy inhibitor, could abolish the effect of clemastine on alleviating myocardial apoptosis. In conclusion, clemastine protected against cardiac structure destruction and function dysfunction, mitochondrial damage, apoptosis, and autophagy and . Moreover, clemastine attenuated myocardial apoptosis by promoting autophagy. This study provides a novel favorable perspective for SIMD therapy.
脓毒症诱导的心肌功能障碍 (SIMD) 与高发病率和死亡率相关；然而，它缺乏靶向治疗。调节心肌细胞自噬可在 SIMD 期间维持细胞内的稳态。氯马斯汀是一种组胺受体抑制剂，可促进自噬和其他有效的生物学功能。然而，氯马斯汀对 SIMD 的影响尚不清楚。本研究旨在探讨氯马斯汀在盲肠结扎穿孔 (CLP) 诱导大鼠和脂多糖 (LPS) 刺激的 H9c2 细胞中心肌细胞损伤中的潜在机制。CLP 手术后 30min 时，通过腹腔内注射氯马斯汀 (10mg/kg、30mg/kg 和 50mg/kg)。评估血清 cTnI 水平和 7 天存活率。使用超声心动图和 H&E 染色评估心功能和结构。TEM 用于检测线粒体超微结构和自噬体。氯马斯汀显著提高了存活率并降低了血清中的 cTnI 产量。氯马斯汀改善了细胞凋亡，改善了线粒体超微结构和，增加了 ATP 含量，降低了动力相关蛋白 1 (DRP1) 的表达，并降低了线粒体 ROS 水平。此外，氯马斯汀处理增加了自噬体浓度、LC3II/LC3I 比率和 Beclin 1 的表达。然而，自噬抑制剂 3-甲基腺嘌呤 (3-MA) 可消除氯马斯汀对减轻心肌细胞凋亡的作用。总之，氯马斯汀可保护心脏结构破坏和功能障碍、线粒体损伤、凋亡和自噬和。此外，氯马斯汀通过促进自噬来减轻心肌细胞凋亡。这项研究为 SIMD 治疗提供了一个新的有利视角。
