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丹酚酸B镁抑制ATP和KCl诱导大鼠主动脉平滑肌细胞内钙的升高 被引量:18

Magnesium lithospermate B inhibits intracellular calcium elevation induced by ATP and KCl in rat vascular smooth muscle cells
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摘要 目的 研究丹酚酸B镁(Magnesium lithospermate B,MLB)对去内皮离体血管舒缩反应以及对血管平滑肌细胞内游离钙浓度[Ca^2+]i的影响。方法 去内皮大鼠胸主动脉血管环等张收缩实验和采用钙离子荧光指示剂Fluo-3,运用F-4500阳离子测定系统动态检测胸主动脉平滑肌细胞[Ca^2+]i。结果 血管舒缩实验显示,无钙或常钙条件下MLB对血管基础张力均无作用。MLB 50~200μmol·L^-1预给药组抑制无钙条件下苯肾上腺素(PE)μmol·L^-1诱导的血管收缩以及常钙条件下KCl60mmol·L^-1诱导的血管收缩,并呈浓度相关性。而钙离子通道阻滞剂维拉帕米(Ver)10μnol·L^-1则完全阻断KCl诱导的血管收缩。在复钙实验中观察到,MLB50~200μmol·L^-1不仅抑制PE1μmol·L^-1“诱导的内钙依赖性血管收缩,而且对复钙后外钙依赖性的血管收缩也有抑制作用。细胞内钙测定实验表明。MLB预孵育的AVSMCs静息态[Ca^2+]i没有变化。无钙条件下,MLB50、100和200μmol·L^-1抑制ATP20μmol·L^-1诱导内钙释放引起的[Ca^2+]i升高,抑制率分别为17.4%、32.4%和61.1%,显示较好的浓度相关性。AVSMCs于常钙条件下用Thapsigargin耗竭钙库后,KCl60mmol·L^-1诱发外钙内流,引起[Ca^2+]i升高,10μmol·L^-1的Ver则能完全阻断这种外钙内流。在MLB预给药组,KCl诱导的[Ca^2+];升高降低,抑制率分别为20.0%、32.8%和52.6%。结论 MLB能够抑制PE、高K^+和复Ca^2+诱导的血管收缩,并能抑制ATP和KCl诱导的血管平滑肌细胞内钙的升高,提示MLB对血管平滑肌细胞内钙的影响可能与抑制细胞内钙释放和电压依赖性钙通道有关。 Aim To investigate the effects of magnesium lithospermate B ( MLB ) on vasoconstriction of denuded aortic rings in MLB on cytosolic vitro, as well as the effects of ([Ca^2+ ]i) in aortic (AVSMCs). Methods in the rat thoracic aortic free calcium concentration vascular smooth muscle cells Isotonic tension was measured rings without endothelium and quantitative changes of [ Ca^2+ ]i were directly monitored in AVSMCs loaded with the fluorescent calcium indicator Fluo-3 using intracellular cation measurement system. tension Results MLB had no effects on resting ring in the presence or absence of extracellular Ca^2+. In rings exposed to 50 ~200 μmol · L^-1 MLB, the isotonic contractions induced by 1 μmol · L^-1 PE were decreased in calcium-free K-H solution. However, in the presence of extracellular Ca^2+ , KCl 60 mmol·L^-1 produced isotonic contractions that were abolished by verapamil 10 μmol · L^-1 or inhibited by pretreatment of 50~200 μmol · L^-1 MLB in a concentration-dependent manner. When administered to the rings precontracted with 1 μmol · L^-1 PE in the absence of extracellular Ca^2 + , a second extracelluar-calcium-dependent vasoconstriction induced by restoration of extracellular Ca2+ was also reduced by pretreatment of 50~200 μmol · L^-1 MLB. Moreover, MLB, at concentration of 50 ~200 μmol · L^-1, produced little effect on AVSMCs [ Ca^2+ ] i in the presence or absence of extracellular Ca^2+ . In AVSMCs exposed to 50 ~200 μmol · L^-1MLB, the inhibitory effects of MLB on [ Ca^2+ ]i induced by 20μmol · L^-1 ATP were concentration-dependent, with decreases ranging from 17.4% to 61.1% in the absence of extracellular Ca^2+. In the presence of extracellular Ca^2+ and thapsigargin, the increases in AVSMCs [ Ca^2+ ] i evoked by 60 μmol · L^-1 KCl were inhibited by pretreatment with MLB (50 ~ 200 μmol · L^-1) or abolished by pretreatment with verapamil (10 μmol · L^-1). Conclusions MLB inhibits vasoconstriction induced by PE, high-K^+ , and re-Ca^2+. MLB also has inhibitory effects on increase of [ Ca^2+]i induced by ATP and high K^+ in AVSMCs. These results indicate that both the blocking effects on calcium release and voltage-dependent calcium channels may be responsible for the effects of MLB on [ Ca^2+ ]i in vascular smooth muscle cells.
作者 田霞 王逸平
出处 《中国药理学通报》 CAS CSCD 北大核心 2006年第3期311-316,共6页 Chinese Pharmacological Bulletin
基金 国家"十五"重大科技专项"创新药物和中药现代化"资助项目(No2003AA2Z3B69)
关键词 丹酚酸B镁 血管收缩 血管平滑肌细胞 细胞内钙 Fluo-3 magnesium lithospermate B vasoconstric-tion vascular smooth muscle cells intracellular freecalcium Fluo-3
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