Background/Aims

Zidovudine (3′-azido-2′,3′-deoxythymidine; AZT) is a first-line drug for treatment of human immunodeficiency virus infection (HIV). However, its application is limited by cardiotoxicity due to cardiomyocyte injury. This study investigated whether Aloe-emodin (AE), an anthraquinone compound, protects against AZT-induced cardiomyocyte toxicity.

Methods

MTT, JC-1 assays and TUNEL were examined to verify the protective effect of AE against AZT-induced cardiomyocyte injury. Western blotting was performed to explore the anti-apoptotic effect of AE using anti-apoptotic proteins p90rsk, p-bad, and bcl-2 and pro-apoptotic proteins apaf-1, cleaved-caspase-3, and cytochrome c.

Results

We observed a protective effect of AE against cell viability decrease and TUNEL positive cells increase induced by AZT, which was counteracted by BI-D1870. Western blot analysis found that AE significantly inhibited cardiomyocyte apoptosis by activating p90rsk/p-bad/bcl-2 signaling pathway. Furthermore, BI-D1870 counteracted the anti-apoptotic effect of AE.

Conclusions

Taken together, these results indicate that AE attenuated AZT-induced cardiomyocyte apoptosis by activating p90rsk.

中文翻译：

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芦荟大黄素通过调节p90rsk/p-bad/bcl-2信号通路减轻齐多夫定引起的新生大鼠心室肌细胞损伤

 背景/目标

Zidovudine (3'-azido-2',3'-deoxythymidine; AZT) 是治疗人类免疫缺陷病毒感染 (HIV) 的一线药物。然而，其应用受到心肌细胞损伤引起的心脏毒性的限制。本研究调查了芦荟大黄素 (AE)（一种蒽醌化合物）是否可以防止 AZT 诱导的心肌细胞毒性。

 方法

通过 MTT、JC-1 测定和 TUNEL 检测来验证 AE 对 AZT 诱导的心肌细胞损伤的保护作用。使用抗凋亡蛋白 p90rsk、 p -bad 和 bcl-2 以及促凋亡蛋白 apaf-1、cleaved-caspase-3 和细胞色素 c 进行蛋白质印迹以探索 AE 的抗凋亡作用。

 结果

我们观察到 AE 对 AZT 诱导的细胞活力下降和 TUNEL 阳性细胞增加具有保护作用，而 BI-D1870 可以抵消这种作用。 Western blot分析发现AE通过激活p90rsk/ p -bad/bcl-2信号通路显着抑制心肌细胞凋亡。此外，BI-D1870 抵消了 AE 的抗凋亡作用。

 结论

综上所述，这些结果表明 AE 通过激活 p90rsk 减弱 AZT 诱导的心肌细胞凋亡。