SKF96365和氯化镍对环匹阿尼酸诱导的大鼠PASMC[Ca^(2+)]_i升高的影响  

Effect of SKF96365 and NiCl_2 on cyclopiazonic acid induced intracellular calcium cation concentration increase in rat distal pulmonary arterial smooth muscle cells

作　　者：彭公永[1] 胡锦兴[1] 邹义敏[1] 彭芳[1] 周玉民[1] 胡国平[1] 赵祝香[1] 

机构地区：[1]广州医科大学附属第一医院/广州呼吸疾病研究所/呼吸疾病国家重点实验室/呼吸疾病国家临床医学研究中心,广东广州510120

出　　处：《重庆医学》2015年第11期1445-1448,共4页Chongqing medicine

基　　金：国家自然科学基金资助项目(81000020);十二五国家科技支撑计划课题资助项目(2013BAI09B09);广东省自然科学基金资助项目(2014A030313486);广州市科技计划资助项目(1563000587);羊城学者科研计划学术骨干资助项目(10A025G);呼吸疾病国家重点实验室青年科学基金支持资助项目(11)

摘　　要：目的研究SKF96365和氯化镍(NiCl2)对环匹阿尼酸(CPA)诱导的大鼠远端肺动脉平滑肌细胞(PASMC)内游离钙离子浓度([Ca2+]i)变化的影响。方法培养大鼠PASMC,运用荧光显微镜和InCyte细胞内钙浓度检测系统观测CPA、SKF96365和NiCl2对PASMC[Ca2+]i的影响。结果含5μmol/L硝苯地平的无钙Krebs溶液孵育PASMC,10μmol/L CPA使PASMC[Ca2+]i短暂小幅升高,恢复细胞外Ca2+至2.5 mmol/L后,10μmol/L CPA使PASMC[Ca2+]i迅速显著升高;50μmol/L SKF96365和500μmol/L NiCl2均能明显抑制10μmol/L CPA引起的PASMC[Ca2+]i升高,但对高钾(60mmol/L KCl)溶液引起的PASMC[Ca2+]i升高无影响。结论 CPA可致大鼠PASMC[Ca2+]i升高,且能被SKF96365和NiCl2阻断,提示CPA可能诱发细胞外Ca2+经钙池操纵性钙通道(SOCC)内流,SKF96365和NiCl2能选择性抑制SOCC活性使经SOCC的Ca2+内流减少。Objective To study the effect of SKF96365 and NiCl2 on cyclopiazonic acid （CPA） induced intracellular calcium cation concentration （[Ca2＋ ]i ） change in rat distal pulmonary arterial smooth muscle cells （PASMC） .Methods The rat distal PASMC were isolated and cultured .The effects of CPA ,SKF96365 and NiCl2 on [Ca2＋ ]i in PASMC were tested by fluorescence microscope and InCyte [Ca2＋ ]i measurement system .Results PASMC were incubated with Ca2＋‐free Krebs solution containing 5μmol/L nifedipine ,10 μmol/L CPA caused a small transient increase in [Ca2＋ ]i ;after restoration of extracellular Ca2＋ to 2 .5 mmol/L ,10 μmol/L CPA caused marked increases in [Ca2＋ ]i in PASMC incubated with Krebs solution containing 5 μmol/L nife‐dipine .Both 50 μmol/L SKF96365 and 500 μmol/L NiCl2 distinctly attenuated the increases in [Ca2＋ ]i caused by 10 μmol/L CPA in PASMC .However ,neither 50 μmol/L SKF96365 nor 500 μmol/L NiCl2 affected the increases in [Ca2＋ ]i caused by 60 mmol/L KCl in PASMC .Conclusion CPA induced increases in [Ca2＋ ]i may related to Ca2＋ release from sarcoplasmic reticulum and the in‐flux of Ca2＋ through store‐operated Ca2＋ channels （SOCC） in rat distal PASMC .Both SKF96365 and NiCl2 could selectively block SOCC and attenuated the influx of Ca2＋ through SOCC in PASMC .

关 键 词：环匹阿尼酸 游离钙离子浓度 肺动脉平滑肌细胞 硝苯地平 钙池操纵性钙通道 大鼠 

分 类 号：R965[医药卫生—药理学]