胡椒碱通过激活小鼠PPAR-γ减轻阿霉素诱导的心脏毒性。

IF 3.5 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL PPAR Research Pub Date : 2019-12-17 eCollection Date: 2019-01-01 DOI:10.1155/2019/2601408

Jie Yan, Si-Chi Xu, Chun-Yan Kong, Xiao-Yang Zhou, Zhou-Yan Bian, Ling Yan, Qi-Zhu Tang

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引用次数: 14

摘要

背景:氧化应激、炎症和心脏细胞凋亡与多柔比星(DOX)诱导的心脏损伤密切相关。据报道，胡椒碱可以抑制巨噬细胞的炎症反应和焦亡。然而，胡椒碱是否能保护小鼠免受dox相关的心脏损伤尚不清楚。本研究旨在探讨胡椒碱是否能抑制dox相关小鼠心脏损伤。方法:DOX组小鼠腹腔注射单剂量DOX (15 mg/kg)，诱导DOX相关性急性心脏损伤。为了研究胡椒碱的保护作用，小鼠在注射DOX前2周开始口服胡椒碱(50 mg/kg，每天18:00)3周。结果:胡椒碱治疗可明显减轻dox致心脏损伤，改善心功能。胡椒碱还能降低DOX小鼠心肌氧化应激、炎症和细胞凋亡。胡椒碱还能提高细胞活力，减少心肌细胞的氧化损伤和炎症因子。我们还发现胡椒碱激活过氧化物酶体增殖激活受体-γ (PPAR-γ)，并且胡椒碱的保护作用被PPAR-γ拮抗剂处理在体内和体外被取消。结论:胡椒碱可通过激活小鼠PPAR-γ抑制dox相关性心脏损伤。

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Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-γ in Mice.

Background: Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice.

Methods: To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection.

Results: Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-γ (PPAR-γ), and the protective effects of piperine were abolished by the treatment of the PPAR-γ antagonist in vivo and in vitro.

Conclusions: Piperine could suppress DOX-related cardiac injury via activation of PPAR-γ in mice.

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来源期刊

PPAR Research MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

6.20

自引率

3.40%

发文量

审稿时长

12 months

期刊介绍： PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.