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槲皮素通过抑制氧化应激保护雷公藤内酯醇诱导的大鼠睾丸间质细胞凋亡。

Protection of Quercetin against Triptolide-induced apoptosis by suppressing oxidative stress in rat Leydig cells.

机构信息

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China.

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, PR China; Central Laboratory, General Clinical Research Center, Nanjing First Hospital, Nanjing 210006, PR China.

出版信息

Chem Biol Interact. 2015 Oct 5;240:38-46. doi: 10.1016/j.cbi.2015.08.004. Epub 2015 Aug 13.

Abstract

Triptolide (TP) is a diterpene triepoxide with variety biological activities, such as anti-inflammatory, anti-cancerogenic, immunomodulatory and pro-apoptotic activities. However, its clinical application was limited by potential toxicity. Quercetin (Que) is a member of flavonoids with anti-oxidant effects. In this study, we aimed to demonstrate the protective effect of Que in TP-induced oxidative stress and decrease of testosterone generation in reproductive damage. Leydig cells were treated with TP (20, 40 and 60 nM), which caused obvious oxidative stress increasing intracellular ROS, decreasing activities and expressions of GPx and SOD. Apoptosis was resulted from depolarization of mitochondrial membrane potential (ΔΨm) and release of cytochrome C (Cyt-C) showing increase of BAX/Bcl-2 ratio, caspase-3 and caspase-9. Treatment of Que (5 μM) prior to triptolide could restore all the TP-induced alteration in a certain dose range indicating that the oxidative stress might be one reason of TP-induced reproductive toxic effect. These results suggest that the compatibility with Que might reduce the TP-induced reproductive toxicity, which provide a probability to extend the usage of TP.

摘要

雷公藤红素(TP)是一种具有多种生物活性的二萜三环氧化合物,具有抗炎、抗癌、免疫调节和促凋亡活性。然而,其临床应用受到潜在毒性的限制。槲皮素(Que)是黄酮类化合物的一种,具有抗氧化作用。在这项研究中,我们旨在证明 Que 在 TP 诱导的氧化应激和睾酮生成减少引起的生殖损伤中的保护作用。Leydig 细胞用 TP(20、40 和 60 nM)处理,导致明显的氧化应激,增加细胞内 ROS,降低 GPx 和 SOD 的活性和表达。线粒体膜电位(ΔΨm)去极化和细胞色素 C(Cyt-C)释放导致细胞凋亡,表现为 BAX/Bcl-2 比值增加,caspase-3 和 caspase-9。在 TP 处理之前用 Que(5 μM)处理可以在一定剂量范围内恢复所有由 TP 引起的改变,表明氧化应激可能是 TP 引起生殖毒性的原因之一。这些结果表明,与 Que 配伍可能会降低 TP 引起的生殖毒性,为扩大 TP 的应用提供了可能性。

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