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氯通道阻断剂对血小板胞浆游离钙和血小板聚集的影响 被引量:4

The effects of chloride channel blockers on thrombocytic cytoplasmic free calcium concentration and platelet aggregation
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摘要 目的 探讨氯通道在血小板胞浆游离钙和血小板聚集功能调节中的作用。方法 新鲜分离人血小板,以凝血酶为诱导剂,观察氯通道阻断剂DIDS、NFA和钙通道阻断剂SK&F96365、Nife dipine对血小板胞浆游离钙和血小板聚集的单独作用和相互作用。结果 氯通道阻断剂DIDS、NFA可以浓度依赖性地抑制凝血酶 ( 1U/ml)诱导的血小板聚集,对静息血小板胞浆游离钙无明显影响;DIDS、SK&F96365、Nifedipine可以明显降低凝血酶诱导的血小板聚集、钙释放和钙内流,与对照组比较,P<0. 05;DIDS与SK&F96365联合,对凝血酶诱导的血小板聚集、钙释放和钙内流的抑制比各自单独抑制作用明显增高(P<0. 05),两者的作用相互增强;DIDS与Nifedipine联合,对凝血酶诱导的血小板钙释放的抑制比各自单独抑制作用明显增高 (P<0. 05 ),两者可相互增强;NFA与SK&F96365联合,对凝血酶诱导的血小板钙释放的抑制比各自的单独作用明显降低 (P<0. 05 ),两者可相互减弱;NFA与Nifedipine联合,对凝血酶诱导的血小板聚集、钙释放和钙内流的抑制比各自的单独作用明显降低(P<0. 05),两者可相互减弱。结论 氯通道阻断剂DIDS、NFA对人静息血小板胞浆钙浓度无影响;DIDS可抑制凝血酶诱导的血小板聚集、钙释放和钙内流,NFA仅抑制凝血酶诱导的钙释放;氯通道阻断剂和? Objective To explore the effects of chloride channels on the regulation of platelet cytoplasmic free calcium concentration (\i) and platelet aggregation (PAG). Methods Freshly separated platelets were activated by thrombin. Chloride channel blockers DIDS or NFA and calcium channel blockers SK&F96365 or nifedipine were added to study the effects on platelet \i and PAG by a single reagent or the combination of reagents and find out the interactions among DIDS, NFA, SK&F96365 and nifedipine. Results Both DIDS and NFA could inhibit the thrombin(1 U/ml) induced PAG in a dose dependent manner, whereas had little effect on resting \i. As compared with the control group, DIDS, SK&F96365 and Nifedipine could significantly reduce the PAG, Ca 2+ release and Ca 2+ influx in thrombin activated platelet (P<0.05). The combination of DIDS and SK&F96365 had greater effects in reducing the PAG, Ca 2+ release and Ca 2+ influx than either reagent alone(P<0.05). The combination of DIDS and nifedipine also had greater effect than each alone in reducing Ca 2+ release (P<0.05). The combination of NFA and SK&F96365 weakened each other’s effect on Ca 2+ release (P<0.05), while NFA and nifedipine weakened each other’s effects on PAG, Ca 2+ release and Ca 2+ influx in thrombin activated platelet (P<0.05). Conclusion DIDS and NFA have no effect on the resting \i and the leak calcium influx of platelet. DIDS can inhibit the Ca 2+ release, Ca 2+ influx and PAG of platelet induced by thrombin, while NFA can only inhibit the Ca 2+ release. The chloride channel and calcium channel blockers have interactions in affecting resting \i and PAG of platelet. The opening of chloride channel can influence the cellular calcium movement of platelet.
出处 《中华血液学杂志》 CAS CSCD 北大核心 2005年第3期170-174,共5页 Chinese Journal of Hematology
基金 广东省自然科学基金团队研究资助项目 ( 2000 ) 广东省重点科技攻关资助项目 ( 99M04810G) 广东省科技计划资助项目(2003C32709)
关键词 血小板聚集 凝血酶 胞浆游离钙 氯通道 诱导 钙内流 联合 钙释放 阻断剂 相互作用 Platelet Free calcium Aggregation Chloride channel blockers Calcium channel blockers
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