Wang Yadi, Zhang Yang, Sun Bo, Tong Qing, Ren Liqun
Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China; The Third Hospital Affiliated to The Jinzhou Medical University, No. 5-2 Heping Road, Jinzhou, Liaoning 120001, China.
Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, 1266 Fujin Road, Changchun, Jilin 130021, China.
Evid Based Complement Alternat Med. 2017;2017:1759385. doi: 10.1155/2017/1759385. Epub 2017 Mar 6.
We investigated the potential protective effect of rutinum (RUT) against pirarubicin- (THP-) induced cardiotoxicity. THP was used to induce toxicity in rat H9c2 cardiomyoblasts. Positive control cells were pretreated with a cardioprotective agent dexrazoxane (DZR) prior to treatment with THP. Some of the cells were preincubated with RUT and a p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, both individually and in combination, prior to THP exposure. At a dose range of 30-70 M, RUT significantly prevented THP-induced reduction in cell viability; the best cardioprotective effect was observed at a dose of 50 M. Administration of RUT and SB203580, both individually as well as in combination, suppressed the elevation of intracellular ROS, inhibited cell apoptosis, and reversed the THP-induced upregulation of TGF-1, p-p38 MAPK, cleaved Caspase-9, Caspase-7, and Caspase-3. A synergistic effect was observed on coadministration of RUT and SB203580. RUT protected against THP-induced cardiotoxicity by inhibition of ROS generation and suppression of cell apoptosis. The cardioprotective effect of RUT appears to be associated with the modulation of the TGF-1-p38 MAPK signaling pathway.
我们研究了芦丁（RUT）对吡柔比星（THP）诱导的心脏毒性的潜在保护作用。使用THP诱导大鼠H9c2心肌成纤维细胞产生毒性。阳性对照细胞在接受THP处理前先用心脏保护剂右丙亚胺（DZR）进行预处理。一些细胞在暴露于THP之前分别或联合用RUT和p38丝裂原活化蛋白激酶（MAPK）抑制剂SB203580进行预孵育。在30 - 70μM的剂量范围内，RUT显著预防了THP诱导的细胞活力降低；在50μM的剂量下观察到最佳的心脏保护作用。单独或联合给予RUT和SB203580均能抑制细胞内活性氧的升高，抑制细胞凋亡，并逆转THP诱导的TGF - 1、磷酸化p38 MAPK、裂解的Caspase - 9、Caspase - 7和Caspase - 3的上调。在联合给予RUT和SB203580时观察到协同作用。RUT通过抑制活性氧生成和抑制细胞凋亡来预防THP诱导的心脏毒性。RUT的心脏保护作用似乎与TGF - 1 - p38 MAPK信号通路的调节有关。
