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首页> 外文期刊>The Journal of toxicological sciences >Characterization of nicardipine hydrochloride-induced cell injury in human vascular endothelial cells
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Characterization of nicardipine hydrochloride-induced cell injury in human vascular endothelial cells

机译:盐酸尼卡地平诱导的人血管内皮细胞损伤的特征

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摘要

Nicardipine hydrochloride (NIC), a dihydropyridine calcium-channel blocking agent, has been widely used for the treatment of hypertension. Especially, nicardipine hydrochloride injection is used as first-line therapy for emergency treatment of abnormally high blood pressure. Although NIC has an attractive pharmacological profile, one of the dose-limiting factors of NIC is severe peripheral vascular injury after intravenous injection. The goal of this study was to better understand and thereby reduce NIC-mediated vascular injury. Here, we investigated the mechanism of NIC-induced vascular injury using human dermal microvascular endothelial cells (HMVECs). NIC decreased cell viability and increased percent of dead cells in a dose-dependent manner (10-30 mu g/mL). Although cell membrane injury was not significant over 9 hr exposure, significant changes of cell morphology and increases in vacuoles in HMVECs were observed within 30 min of NIC exposure (30 mu g/mL). Autophagosome labeling with monodansylcadaverine revealed increased autophagosomes in the NIC-treated cells, whereas caspase 3/7 activity was not increased in the NIC-treated cells (30 mu g/mL). Additionally, NIC-induced reduction of cell viability was inhibited by 3-methyladenine, an inhibitor of autophagosome formation. These findings suggest that NIC causes severe peripheral venous irritation via induction of autophagic cell death and that inhibition of autophagy could contribute to the reduction of NIC-induced vascular injury.
机译:盐酸尼卡地平(NIC)是一种二氢吡啶类钙通道阻滞剂,已被广泛用于治疗高血压。特别是,尼卡地平盐酸盐注射液被用作紧急治疗异常高血压的一线疗法。尽管NIC具有诱人的药理作用,但NIC的剂量限制因素之一是静脉注射后严重的外周血管损伤。这项研究的目的是更好地理解并减少NIC介导的血管损伤。在这里,我们调查了使用人皮肤微血管内皮细胞(HMVECs)NIC诱导的血管损伤的机制。 NIC以剂量依赖性(10-30μg / mL)降低细胞活力并增加死细胞百分比。尽管在暴露9小时后细胞膜损伤并不显着,但在NIC暴露(30μg / mL)后30分钟内,观察到HMVEC中细胞形态的显着变化和液泡的增加。用单丹磺酰尸胺标记自噬体表明,在NIC处理的细胞中自噬体增加,而在NIC处理的细胞中胱天蛋白酶3/7活性未增加(30μg / mL)。此外,NIC诱导的细胞活力降低受到3-甲基腺嘌呤(一种自噬体形成抑制剂)的抑制。这些发现表明,NIC通过诱导自噬细胞死亡而引起严重的外周静脉刺激,抑制自噬可能有助于减轻NIC引起的血管损伤。

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