Department of Cardiology, Jiangxi Provincial People's Hospital, No, 92 Aiguo Road, Donghu District, Nanchang, 330006, Jiangxi, People's Republic of China; Jiang Xi Provincial Institute of Cardiovascular Diseases, No, 92 Aiguo Road, Donghu District, Nanchang, 330006, Jiangxi, People's Republic of China.
Department of Cardiology, Jiangxi Provincial People's Hospital, No, 92 Aiguo Road, Donghu District, Nanchang, 330006, Jiangxi, People's Republic of China.
Toxicol Lett. 2018 Oct 1;295:205-211. doi: 10.1016/j.toxlet.2018.06.1219. Epub 2018 Jun 28.
Doxorubicin (Dox) is limited in its use because of its adverse effect of inducing irreversible heart dysfunction. Innate immune factors, including toll-like receptors (TLRs), play important roles in most cardiac diseases and doxorubicin-induced cardiotoxicity. In this study, subjects were divided into the following groups: healthy controls (n = 62), HF group (n = 60), Dox group (n = 82), and Dox-HF group (n = 32). Expressions of TLR mRNAs in peripheral blood mononuclear cells were detected by RT-PCR. Western blotting was used to quantify protein expressions of Peripheral blood mononuclear cells (PBMCs) TLRs and their downstream signal proteins. The release of inflammatory factors was detected by ELISA. Results indicated that TLR2 was increased and TLR3 was decreased between the control group and Dox group, and between the Dox group and Dox-HF group. Serum inflammatory factors were comparable between the HF group, the Dox group, and the Dox-HF group. This study suggested that TLR2 and TLR3 are up- and down-regulated, respectively, in doxorubicin-treated patients who develop heart dysfunctions. This may suggest a predictive role for TLR2-TLR3 imbalance in doxorubicin-induced heart failure.
多柔比星（Dox）由于其诱导不可逆性心脏功能障碍的不良反应而受到限制。先天免疫因素，包括 Toll 样受体（TLR），在大多数心脏疾病和多柔比星诱导的心脏毒性中发挥重要作用。在这项研究中，受试者被分为以下几组：健康对照组（n=62）、HF 组（n=60）、Dox 组（n=82）和 Dox-HF 组（n=32）。通过 RT-PCR 检测外周血单个核细胞中 TLR mRNAs 的表达。Western blot 用于定量 TLRs 及其下游信号蛋白在 PBMCs 中的蛋白表达。通过 ELISA 检测炎症因子的释放。结果表明，与对照组相比，Dox 组和 Dox-HF 组 TLR2 增加，TLR3 减少。HF 组、Dox 组和 Dox-HF 组之间血清炎症因子无差异。本研究表明，在发生心脏功能障碍的多柔比星治疗患者中，TLR2 和 TLR3 分别上调和下调。这可能提示 TLR2-TLR3 失衡在多柔比星诱导的心力衰竭中有预测作用。
