红参通过激活 Nrf2 通路抑制细胞死亡,从而预防多柔比星诱发的心肌病。

IF 3.2 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Naoki Yoshikawa, Naoto Hirata, Yuichiro Kurone, Sadahiko Shimoeda
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引用次数: 0

摘要

背景:多柔比星(DXR)是一种有效的化疗药物:多柔比星(DXR)是一种有效的化疗药物。多柔比星诱发的心肌病(DICM)是多柔比星的一个主要局限,是一种治疗选择有限的并发症。我们以前曾报道过红参(将栽培六年以上的三七根蒸煮并晒干;RGin)对治疗 DICM 有益。然而,RGin 的作用机制仍不清楚。本研究探讨了RGin治疗DICM的作用机制:将四周大的 DBA/2 小鼠分为:载体组、DXR 组、RGin 组和 DXR + RGin 组(n = 10/组)。小鼠接受 DXR(4 毫克/千克,每周一次,累计 20 毫克/千克,静注)或 RGin(0.5 克/千克,每周三次,静注)治疗。为了评估疗效,测量了存活率和左心室射血分数(LVEF),以衡量心脏功能,并对心肌细胞进行了马森三色染色。为研究其作用机制,对核因子红细胞2相关因子2(Nrf2)、血红素加氧酶1、转铁蛋白受体(TfR)和其他相关蛋白的表达进行了Western印迹分析。数据使用 Easy R 软件进行分析。组间比较采用单因素方差分析,并使用事后Tukey检验进行分析。生存率采用 Kaplan-Meier 法估算,并采用对数秩检验进行比较。P 结果RGin治疗可延长生存期并防止LVEF降低。在 DXR 组中,Nrf2 未被激活,细胞死亡加速。此外,TfR水平升高,表明铁代谢异常。然而,DXR + RGin 组则显示出 Nrf2 通路被激活,心肌细胞死亡被抑制。此外,TfR 的表达没有增加,表明铁代谢没有异常。因此,RGin 在 DICM 中的作用机制包括通过激活 Nrf2 通路提高抗氧化活性和抑制细胞死亡:结论:RGin是一种治疗DICM的有效候选药物。结论:RGin 是治疗 DICM 的有效候选药物,其疗效得益于 Nrf2 通路的激活,该通路可增强抗氧化活性并抑制细胞死亡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Red ginseng prevents doxorubicin-induced cardiomyopathy by inhibiting cell death via activating the Nrf2 pathway.

Background: Doxorubicin (DXR) is an effective chemotherapeutic agent. DOX-induced cardiomyopathy (DICM), a major limitation of DXR, is a complication with limited treatment options. We previously reported that Red Ginseng (steamed and dried the root of Panax Ginseng cultivated for over six years; RGin) is beneficial for the treatment of DICM. However, the mechanism underlying the action of RGin remains unclear. In this study, we investigated the mechanism of action underlying the efficacy of RGin in the treatment of DICM.

Methods: Four-week-old DBA/2 mice were divided into: vehicle, DXR, RGin, and DXR + RGin (n = 10/group). Mice were treated with DXR (4 mg/kg, once a week, accumulated 20 mg/kg, i.p.) or RGin (0.5 g/kg, three times a week, i.p.). To evaluate efficacy, the survival rate and left ventricular ejection fraction (LVEF) were measured as a measure of cardiac function, and cardiomyocytes were subjected to Masson trichrome staining. To investigate the mechanism of action, western blotting was performed to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1, transferrin receptor (TfR), and other related proteins. Data were analyzed using the Easy R software. Between-group comparisons were performed using one-way analysis of variance and analyzed using a post-hoc Tukey test. Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test. P < 0.05 was considered statistically significant in all analyses.

Results: RGin treatment prolongs survival and protects against reduced LVEF. In the DXR group, Nrf2 was not activated and cell death was accelerated. Furthermore, there was an increase in the TfR levels, suggesting abnormal iron metabolism. However, the DXR + RGin group showed activation of the Nrf2 pathway and suppression of myocardial cell death. Furthermore, there was no increase in TfR expression, suggesting that there were no abnormalities in iron metabolism. Therefore, the mechanism of action of RGin in DICM involves an increase in antioxidant activity and inhibition of cell death through activation of the Nrf2 pathway.

Conclusion: RGin is a useful therapeutic candidate for DICM. Its efficacy is supported by the activation of the Nrf2 pathway, which enhances antioxidant activity and inhibits cell death.

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来源期刊
Cardio-oncology
Cardio-oncology Medicine-Cardiology and Cardiovascular Medicine
CiteScore
5.00
自引率
3.00%
发文量
17
审稿时长
7 weeks
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