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丹皮酚通过调节 miR-1 和 PI3K/AKT 通路对表阿霉素诱导的心脏损伤的心脏保护作用。

Cardioprotective effect of paeonol against epirubicin-induced heart injury via regulating miR-1 and PI3K/AKT pathway.

机构信息

Department of Pharmacy, The Second Hospital of Shandong University, Jinan, China.

Pediatric Surgery, The Second Hospital of Shandong University, Jinan, China.

出版信息

Chem Biol Interact. 2018 Apr 25;286:17-25. doi: 10.1016/j.cbi.2018.02.035. Epub 2018 Mar 2.

Abstract

Cardiotoxicity is a dose-dependent side effect of epirubicin that restricts its clinical utility in cancer chemotherapy. Paeonol is an active constituent with various biological activities, including the protection of antineoplastic-induced toxicities. In the present study, we investigated the protective effect of paeonol on epirubicin-induced cardiotoxicity and explored the underlying mechanism. A series of methods were used including a MTT assay, flow cytometry, echocardiography, TUNEL staining, a dual-luciferase reporter assay, immunofluorescence, RT-PCR and Western blotting. The results indicate that paeonol improves cardiac dysfunction, relieves histopathological changes, alleviates inflammation, reduces myocardial apoptosis and increases autophagy. Further studies suggest that paeonol upregulates the decreased expression of miR-1 caused by epirubicin and thus inhibits the activation of PI3K/AKT/mTOR and NF-κB pathways. In conclusion, paeonol effectively ameliorates myocardial injury by increasing miR-1 expression to suppress the PI3K/AKT/mTOR and NF-kB signalling pathways.

摘要

蒽环类药物的心脏毒性是剂量依赖性的副作用,限制了其在癌症化疗中的临床应用。丹皮酚是一种具有多种生物活性的活性成分,包括保护抗肿瘤诱导的毒性。在本研究中,我们研究了丹皮酚对表柔比星诱导的心脏毒性的保护作用,并探讨了其潜在的机制。我们使用了一系列方法,包括 MTT 测定、流式细胞术、超声心动图、TUNEL 染色、双荧光素酶报告基因测定、免疫荧光、RT-PCR 和 Western blot。结果表明,丹皮酚改善了心脏功能障碍,缓解了组织病理学变化,减轻了炎症,减少了心肌细胞凋亡,增加了自噬。进一步的研究表明,丹皮酚上调了表柔比星引起的 miR-1 表达降低,从而抑制了 PI3K/AKT/mTOR 和 NF-κB 通路的激活。综上所述,丹皮酚通过增加 miR-1 的表达来有效改善心肌损伤,从而抑制 PI3K/AKT/mTOR 和 NF-kB 信号通路。

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