Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
Department of Plastic Surgery, General Hospital of Chinese PLA, Beijing 100853, P.R. China.
Mol Med Rep. 2021 Jul;24(1). doi: 10.3892/mmr.2021.12174. Epub 2021 Jun 3.
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 g/ml), TA (10 M) 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.
脓毒症诱导的心肌功能障碍是脓毒症多器官功能障碍的特征之一，与极高的死亡率相关，其特征为心肌顺应性受损。迄今为止，治疗脓毒症的有效治疗选择很少。据报道，没食子酸（TA）在脓毒症中具有保护作用；然而，TA 保护脓毒症性心脏损伤的潜在机制仍难以捉摸。本研究旨在探讨 TA 缓解脂多糖（LPS）诱导的 H9C2 心肌细胞凋亡的潜在作用及其潜在机制。用 LPS（15μg/ml）、TA（10μM）和 TA+LPS 处理 H9C2 细胞；对照组仅用培养基处理。采用流式细胞术、逆转录-定量 PCR（RT-qPCR）和 Western blot 分析检测细胞凋亡。此外，还评估了细胞内活性氧（ROS）、丙二醛和烟酰胺腺嘌呤二核苷酸磷酸的水平。Western blot 和 RT-qPCR 还用于检测内质网（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。TA 处理后，ERS 相关功能蛋白，包括激活转录因子 6、蛋白激酶样 ER 激酶、肌醇需求酶 1、剪接 X 盒结合蛋白 1 和 C/EBP 同源蛋白的表达受到抑制。此外，TA 处理后，ERS 相关凋亡蛋白，包括 c-Jun N-末端激酶、Bax、细胞色素 c、半胱天冬酶-3、半胱天冬酶-12 和半胱天冬酶-9 的表达水平降低。此外，用 ROS 抑制剂 N-乙酰半胱氨酸处理后，TA 对 LPS 诱导的 H9C2 细胞的保护作用部分受到抑制，这表明 ROS 介导 ERS 相关的细胞凋亡，TA 能够降低 ROS 介导的 ERS 相关的细胞凋亡。综上所述，TA 对 LPS 诱导的 H9C2 细胞凋亡的保护作用可能与改善 ROS 介导的 ERS 有关。这些发现可能有助于开发抑制心肌细胞损伤进展的潜在新治疗方法。
