脓毒症引起的心肌功能障碍是脓毒症多器官功能障碍的特征之一,这与极高的死亡率相关,其特征是心肌顺应性受损。迄今为止,很少有有效的治疗方案可用于治疗脓毒症。据报道,单宁酸(TA)在败血症期间具有保护作用;然而,TA预防感染性心脏损伤的潜在机制仍然难以捉摸.本研究调查了TA在减轻脂多糖(LPS)诱导的H9C2心肌细胞凋亡中的潜在作用和潜在机制。H9C2细胞用LPS(15μg/ml)处理,TA(10μM)和TA+LPS;对照细胞仅用培养基处理。使用流式细胞术测量细胞凋亡,逆转录-定量PCR(RT-qPCR)和蛋白质印迹分析。此外,细胞活性氧(ROS)的水平,丙二醛和烟酰胺腺嘌呤二核苷酸磷酸进行评估。蛋白质印迹和RT-qPCR也用于检测内质网(ER)应激相关功能蛋白的表达水平。本研究结果表明,TA降低了LPS诱导的H9C2细胞损伤的程度,包括抑制ROS产生和ER应激(ERS)相关的细胞凋亡。ERS相关功能蛋白,包括激活转录因子6,蛋白激酶样内质网激酶,对TA处理的需要肌醇的酶1,剪接的X盒结合蛋白1和C/EBP同源蛋白被抑制。此外,ERS相关凋亡蛋白的表达水平,包括c-Jun氨基末端激酶,Bax,细胞色素c,用TA处理后,caspase‑3,caspase‑12和caspase‑9减少。此外,用ROS抑制剂N-乙酰半胱氨酸处理后,TA对LPS诱导的H9C2细胞的保护作用被部分抑制,这表明ROS介导的ERS相关凋亡和TA能够减少ROS介导的ERS相关凋亡。总的来说,本研究结果表明,TA对LPS诱导的H9C2细胞凋亡的保护作用可能与ROS介导的ERS的改善有关。这些发现可能有助于开发潜在的新型治疗方法来抑制心肌细胞损伤的进展。
Sepsis‑induced myocardial dysfunction is one of the features of multiple organ dysfunction in sepsis, which is associated with extremely high mortality and is characterized by impaired myocardial compliance. To date, there are few effective treatment options available to cure sepsis. Tannic acid (
TA) is reportedly protective during sepsis; however, the underlying mechanisms by which
TA protects against septic heart injury remain elusive. The present study investigated the potential effects and underlying mechanisms of TA in alleviating lipopolysaccharide (LPS)‑induced H9C2 cardiomyocyte cell apoptosis. H9C2 cells were treated with LPS (15 µg/ml),
TA (10 µM) and
TA + LPS; control cells were treated with medium only. Apoptosis was measured using flow cytometry, reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis. Additionally, the levels of cellular reactive oxygen species (ROS), malondialdehyde and nicotinamide adenine dinucleotide phosphate were evaluated. Western blotting and RT‑qPCR were also employed to detect the expression levels of endoplasmic reticulum (ER) stress‑associated functional proteins. The present findings demonstrated that
TA reduced the degree of LPS‑induced H9C2 cell injury, including inhibition of ROS production and ER stress (ERS)‑associated apoptosis. ERS‑associated functional proteins, including activating transcription factor 6, protein kinase‑like ER kinase, inositol‑requiring enzyme 1, spliced X box‑binding protein 1 and C/EBP‑homologous protein were suppressed in response to TA treatment. Furthermore, the expression levels of ERS‑associated apoptotic proteins, including c‑Jun N‑terminal kinase, Bax, cytochrome c, caspase‑3, caspase‑12 and caspase‑9 were reduced following treatment with TA. Additionally, the protective effects of TA on LPS‑induced H9C2 cells were partially inhibited following treatment with the ROS inhibitor N‑acetylcysteine, which demonstrated that ROS mediated ERS‑associated apoptosis and TA was able to decrease ROS‑mediated ERS‑associated apoptosis. Collectively, the present findings demonstrated that the protective effects of
TA against LPS‑induced H9C2 cell apoptosis may be associated with the amelioration of ROS‑mediated ERS. These findings may assist the development of potential novel therapeutic methods to inhibit the progression of myocardial cell injury.