Department of Basic Medical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj 11942, Saudi Arabia.
Molecules. 2020 Nov 29;25(23):5622. doi: 10.3390/molecules25235622.
Sepsis aggregates undesirable immune response causing depression of ventricular myocardium and diastolic dysfunction. This present study examined the effect of a plant-derived flavone tangeretin (TG) on autophagy and reduction in myocardial dysfunction. The sepsis was induced by cecum ligation and puncture (CLP) in male Sprague-Dawley rats. Abnormal changes were seen in the heart after the sepsis induction. These abnormalities were analyzed based on the cardiac markers, namely Cardiac myosin light chain-1 (cMLC1) and Cardiac troponin I (cTnl), echocardiography, and plasma parameters, like Lactate dehydrogenase (LDH) and Creatinine kinase (CK). Microanatomy of the heart was studied using hematoxylin and eosin stained histopathological samples of cardiac tissue. Western blot technique was used to detect the nature and extent of protein with the amount of a specific RNA (gene expression) in the cardiac homogenate. Oxidative damage was analyzed using redox marker, reduced glutathione. This study successfully showed that TG attenuated sepsis-induced myocardial dysfunction by inhibiting myocardial autophagy via silencing the Phosphatase and tensin homolog (PTEN) expression and acting on the AKT/mTOR pathway. The present findings supported that TG is a novel cardioprotective therapeutic target for sepsis induced myocardial dysfunction.
脓毒症会聚集不良免疫反应，导致心室心肌抑制和舒张功能障碍。本研究探讨了一种植物衍生的类黄酮川陈皮素（TG）对自噬和心肌功能障碍减少的影响。雄性 Sprague-Dawley 大鼠通过盲肠结扎和穿孔（CLP）诱导脓毒症。脓毒症诱导后，心脏出现异常变化。这些异常根据心脏标志物（即肌球蛋白轻链-1（cMLC1）和肌钙蛋白 I（cTnl））、超声心动图和血浆参数（如乳酸脱氢酶（LDH）和肌酸激酶（CK））进行分析。使用心脏组织的苏木精和伊红染色组织病理学样本研究心脏的微观解剖结构。使用 Western blot 技术检测心脏匀浆中特定 RNA（基因表达）的数量的蛋白质的性质和程度。使用氧化还原标志物还原型谷胱甘肽分析氧化损伤。这项研究成功表明，TG 通过沉默磷酸酶和张力蛋白同源物（PTEN）表达并作用于 AKT/mTOR 途径，抑制心肌自噬，从而减轻脓毒症引起的心肌功能障碍。这些发现支持 TG 是脓毒症诱导的心肌功能障碍的一种新型心脏保护治疗靶点。
