尼氟灭酸对糖尿病人血小板胞浆游离钙及聚集功能的影响  

Effects of Niflumic Acid on Thrombocytic Cytoplasmic Free Calcium and Platelet Aggregation in Patients with Diabetes Mellitus

作　　者：聂大年[1] 尹松梅[1] 谢双锋[1] 王晓刚[1] 李益清[1] 马丽萍[1] 王秀菊[1] 吴裕丹[1] 冯坚红[1] 

机构地区：[1]中山大学附属第二医院血液内科,广东广州510120

出　　处：《中山大学学报（医学科学版）》2006年第5期533-536,共4页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省科技计划项目(2003C32709);广东省重点攻关项目(99M04810G)

摘　　要：【目的】探讨糖尿病人血小板胞浆游离钙([Ca2+]i)、血小板聚集率变化及氯通道阻断剂尼氟灭酸对其的影响。【方法】用Fura-2荧光测钙技术检测血小板[Ca2+]i,血小板聚集仪检测血小板聚集率,观察氯通道阻断剂尼氟灭酸、钙通道阻断剂硝苯地平及两者联合对糖尿病人的血小板[Ca2+]i、血小板聚集率的作用。【结果】①糖尿病人血小板聚集率为(74.9±13.7)%,高于正常人(P<0.05);糖尿病人的静息血小板[Ca2+]i值、钙释放、钙內流分别为(124．5±38．1)nmol／L、(497．1±95．1)nmol/L、(354.3±75.0)nmol/L,均高于正常人(P均<0.05);②尼氟灭酸及硝苯地平抑制血小板钙内流呈浓度依赖性,半数抑制浓度(IC50)的尼氟灭酸(50μmol/L)对糖尿病人血小板钙内流的抑制率为(54.7±14.5)%,对血小板聚集率的抑制率为(32.3±21.4)%;IC50的硝苯地平(7.5μmol/L)对糖尿病人血小板钙内流的抑制率为(17.9±11.9)%,对血小板聚集率的抑制率为(32.3±20.4)%;③尼氟灭酸联合硝苯地平对糖尿病人血小板钙有抑制作用,联合作用时尼氟灭酸对钙内流抑制率为(51.9±12.8)%;硝苯地平对钙内流抑制率为(12.4±8.5)%(P均<0.05),两者间不存在交互效应。【结论】糖尿病人血小板聚集率、静息血小板[Ca2+]i及钙运动均高于正常人,血小板呈高反应状态。尼氟灭酸可抑制糖尿病人血小板聚集和钙内流,可能与血小板膜存在对尼氟灭酸敏感的氯通道有关。尼氟灭酸与硝苯地平联合对糖尿病患者的血小板钙运动无协同及遏制作用。[Objective] To study the effects of niflumic acid （NFA） on the thrombocytic cytoplasmic free calcium [Ca^2＋]i and platelet aggregation rate （PAG） in diabetic patients. [Methods ] Thrombocytic [Ca^2＋]i was detected by Fura-2 fluorescent technique, and PAG was detected by platelet aggregometer. We studied the effects of NFA, a chloride channel blocker, nifedipine, a calcium channel blocker, and their combining effects on thrombocytic [Ca^2＋]i and PAG in diabetic patients respectively. [Results] ① The PAG and [Ca^2＋]i in diabetic patients were significantly higher than that in control group. The platelet resting [Ca^2＋]i, Ca^2＋ release and Ca^2＋ influx in diabetic patients were higher than the control group. ② NFA and Nifedipine reduced the platelet Ca^2＋ influx which induced by thrombin and these effects were dose-dependent. The concentration producing 50% inhibition （IC50） of NFA was 50 μmol/L, the inhibition rate of thrombocytic [Ca^2＋]i was （54.7±14.5）%, and the inhibition rate of PAG was （32.3±21.4）% when the concentration of NFA was 50 μmol/L. The IC50 of Nifedipine was 7.5 μmol/L, the inhibition rate of thrombocytic [Ca^2＋]i was （17.9±11.9）% and the inhibition rate of PAG was （32.3±20.4）% when the concentration of nifedipine was 7.5 μmol/L, ③NFA（50 μmol/L） combining with nlfedipine （7.5 μmol/L） inhibited platelet Ca^2＋ influx induced by thrombin in diabetes patients. The effects of NFA and nifedpine were independent. [Conclusions ] Platelets in patients with diabetes are hyperactive. NFA reduces the PAG and platelet [Ca^2＋]i influx by blocking the chloride channels on platelet membrane in diabetic patients. There are no interactions between NFA and nifedipine on the movement of platelet [Ca^2＋]i.

关 键 词：胞浆游离钙 尼氟灭酸 硝苯地平 血小板 糖尿病 

分 类 号：R587.1[医药卫生—内分泌]