Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China.
Mol Med Rep. 2021 Mar;23(3). doi: 10.3892/mmr.2021.11858. Epub 2021 Jan 26.
Shengxian decoction (SXT) is a traditional Chinese medicine that is clinically used for treating cardiovascular diseases. It is known for its beneficial effect on cardiomyocyte injuries, some of which can be induced by anticancer agents including doxorubicin (DOX). To determine the molecular mechanisms involved in the cardioprotective effects of SXT, DOX‑induced H9c2 cells were analyzed for apoptosis and expression levels of apoptosis biomarkers. Cell viability and apoptosis were measured by CCK‑8 and flow cytometry. Triggering receptors expressed on myeloid cells 1 (TREM1), cleaved caspase‑3, survivin and NF‑κBp65 expression levels were measured by reverse transcription‑quantitative PCR and/or western blotting. A total of 30 adult male Sprague‑Dawley rats were randomly allocated into five groups (n=6 each); control group receiving 0.9% saline, 1 DOX group receiving 2.5 mg/kg of DOX and 3 DOX + SXT groups, receiving a DOX dose equivalent to the DOX‑only group and either 0.4, 0.8 or 1.6 g/kg of SXT. It was found that DOX increased apoptosis and NF‑κB activation of H9c2 cells by increasing TREM1 expression and that SXT inhibited apoptosis and NF‑κB activation of H9c2 cells induced by DOX or overexpression. SXT also significantly reversed DOX‑induced cardiotoxicity in rats. The results suggested that the protective effects of SXT against DOX‑induced apoptosis may be attributed to its downregulation of TREM1.
圣仙汤(SXT)是一种临床用于治疗心血管疾病的中药。它以对心肌细胞损伤的有益作用而闻名,其中一些损伤是由包括阿霉素(DOX)在内的抗癌药物引起的。为了确定 SXT 的心脏保护作用的分子机制,分析了 DOX 诱导的 H9c2 细胞凋亡和凋亡生物标志物的表达水平。通过 CCK-8 和流式细胞术测定细胞活力和细胞凋亡。通过逆转录定量 PCR 和/或 Western blot 测定触发髓样细胞表达的受体 1(TREM1)、裂解的半胱氨酸天冬氨酸蛋白酶-3、存活素和 NF-κBp65 的表达水平。总共 30 只成年雄性 Sprague-Dawley 大鼠随机分为五组(每组 n=6);对照组给予 0.9%生理盐水,1 DOX 组给予 2.5mg/kg 的 DOX 和 3 DOX+SXT 组,给予与 DOX 组等效的 DOX 剂量,以及 0.4、0.8 或 1.6g/kg 的 SXT。结果发现,DOX 通过增加 TREM1 的表达增加了 H9c2 细胞的凋亡和 NF-κB 激活,而 SXT 抑制了 DOX 或 TREM1 过表达诱导的 H9c2 细胞的凋亡和 NF-κB 激活。SXT 还显著逆转了 DOX 诱导的大鼠心脏毒性。结果表明,SXT 对 DOX 诱导的凋亡的保护作用可能归因于其对 TREM1 的下调。