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槲皮素填充的脂质体对电离辐射处理的大鼠胸主动脉平滑肌细胞上BKCa的作用

SOLOVIEV Anatoly^*, TISHKIN Sergey, KYRYCHENKO Sergey

乌克兰医学科学院药理和毒理学研究所，基辅 03057，乌克兰

摘要

本文旨在研究槲皮素填充的卵磷脂脂质体(quercetin-filled phosphatidylcholine liposomes, PCL-Q)对非致死性全身电离辐 射处理的大鼠胸主动脉平滑肌细胞(smooth muscle cells, SMCs)上的大电导钙离子依赖性钾通道(large conductance Ca2+-dependent K+ channels, BKCa)的作用。我们使用膜片钳技术，观察到去极化阶跃脉冲刺激的SMCs 上出现外向K+ 电流，该电流对paxilline (BKCa 的一种特异性抑制剂)敏感，因此认为该电流主体为BKCa 电流。相对正常对照大鼠，辐照处理大鼠SMCs 的BKCa 电流 幅度明显减小。这种通道抑制效应在辐照后第9 天表现显著，且在整个30 天的实验期间是逐渐增强的。辐照处理大鼠的SMCs 的血管舒张能力可能因此而减弱。在本实验中，PCL-Q 有效地恢复了辐照后SMCs 的BKCa 功能。而PCL-Q 的组分，单一 的槲皮素或“空白”的脂质体(PCL)恢复BKCa 功能的能力较二者的组合体有明显的减弱。上述结果表明，PCL-Q 能恢复辐 照处理后SMCs 的BKCa 正常功能。PCL-Q 的保护能力可能来源于其抗氧化、修复质膜和抑制蛋白激酶C 的作用。由此可见， 这种脂胶囊化的黄酮类化合物—— PCL-Q 是一种在放射性事故急救和放疗副作用防治方面颇具前景的药物。

关键词： 平滑肌; 辐射; 活性氧; 钾通道; 槲皮素; 脂质体; 蛋白激酶C

分类号：R331.3+3；R339.5+7

Quercetin-filled phosphatidylcholine liposomes restore abnormalities in rat thoracic aorta BKCa channel function following ionizing irradiation

SOLOVIEV Anatoly^*, TISHKIN Sergey, KYRYCHENKO Sergey

Institute of Pharmacology and Toxicology, Academy of Medical Science, Kiev 03057, Ukraine

Abstract

The goal of the present study was to investigate the effects of quercetin-filled phosphatidylcholine liposomes (PCL-Q) on the currents carried by large conductance Ca2+-dependent K+ channels (BKCa) in rat thoracic aorta following non-fatal whole-body ionizing irradiation. Using patch-clamp technique, it is found that the outward K+ currents of isolated smooth muscle cells (SMCs) stimulated by depolarizing voltage steps were sensitive to BKCa inhibitor, paxilline, and this kind of outward K+ currents in SMCs from irradiated animals demonstrated a significant decrease in amplitude. Radiation-induced BKCa suppression was evident 9 days postirradiation and progressively increased over 30 days of experimental period. Thus, the vasorelaxing force of these SMCs may be diminished following irradiation. PCL-Q effectively restored BKCa function in post-irradiated SMCs. It is noteworthy that the constituents of PCL-Q, i.e., free quercetin (Q) and “empty” liposomes (PCL), being taken separately, showed a decreased ability to recover BKCa function as compared with combined composition. These results suggest that PCL-Q is able to regain normal function of BKCa following irradiation. The protective effects of PCL-Q can be explained by its antioxidant and membrane repairing properties as well as its ability to inhibit protein kinase C activity. Thus, the lipid encapsulation of flavonoid, PCL-Q, appears to be a potential medication in the case of ionizing irradiation accident, and for the patients with neoplasm who have to receive external radiotherapy as well.

Key words: smooth muscle; radiation; reactive oxygen species; potassium channels; quercetin; liposomes; protein kinase C

收稿日期：2008-12-31　　录用日期：2009-04-15

通讯作者：SOLOVIEV Anatoly　　E-mail: tonysolpharm@ukrpost.ua

引用本文：

SOLOVIEV Anatoly, TISHKIN Sergey, KYRYCHENKO Sergey. 槲皮素填充的脂质体对电离辐射处理的大鼠胸主动脉平滑肌细胞上BKCa的作用[J]. 生理学报 2009; 61 (3): 201-210.

SOLOVIEV Anatoly, TISHKIN Sergey, KYRYCHENKO Sergey. Quercetin-filled phosphatidylcholine liposomes restore abnormalities in rat thoracic aorta BKCa channel function following ionizing irradiation. Acta Physiol Sin 2009; 61 (3): 201-210 (in Chinese with English abstract).