摘要
目的 探讨二氢吡啶类钙拮抗剂 2 ,6 二甲基 4 (3 硝基苯基 ) 1,4 二氢 3,5 吡啶二羧酸 3 甲酯 5 正戊酯(MN92 0 2 )增强红细胞 (RBC)变形性的可能机制。方法 角叉菜胶复制大鼠血栓模型 ;荧光染料Fura 2负载 ,荧光分光度法测定RBC内游离Ca2 +浓度 ;紫外分光光度法测定脂质过氧化产物丙二醛 (MDA)以及膜蛋白交联形成的共轭双烯的含量 ;孔雀绿法测定Ca MgATPase活力。 结果 MN92 0 2在本实验剂量范围内 ,剂量依赖地降低RBCMDA含量 (r =0 998) ,抑制膜共轭双烯的形成。MN92 0 2 0 1、1μmol·kg-1能增强全血SOD活力 ;有效抑制角叉菜胶引起的RBC内Ca2 +浓度的升高 ,但对RBCCa MgATPase活性无影响。结论 MN92 0 2阻断Ca2 +内流、抑制脂质过氧化是其改善RBC变形性的主要机制。
AIM To investigate the effects of MN9202 on RBC cytosolic free Ca 2+ transport and lipid peroxidation of RBC membrane in the thrombosis rats. METHODS Forty eight male SD rats were assigned into six groups. One was under normal control and the other five groups were injected with carrageenan sc . in paw to induced thrombus in tail. Saline, vehicle and MN9202 at dosage of 0 01, 0 1, 1 μmol·kg -1 were injected ip . 24,1 h before, and 24 h after carrageenan treatment. Ca 2+ sensitive fluorescent indicator, Fura 2AM was used to determine cytosolic free Ca 2+ . Ca Mg ATPase was assayed by Malachite green. Superoxide dismutase (SOD), malondialdehyde (MDA) and membrane conjugation diene (MCD) were assayed by nitro blue tetrazolium reaction, Thriobarbituric Acid reaction(TBA) and UV VIS spectrophotometer in 233 nm, respectively.RESULTS MN9202 at dosage of 0 1 ,1 μmol·kg -1 decreased RBC cytosolic free Ca 2+ ( F 335 / F 385 ) (1 67±0 20,1 56±0 20 vs 1 87±0 16, P <0 05, P <0 01 ) and elevated SOD of RBC (10 3±0 9, 10 2±91 0 vs 7 9±0 9, P <0 05). Ca Mg ATPase was increased significantly by carragennan but showed no obvious changes by MN9202. Each dosage of MN9202 expressed inhibitory effect on formation of MDA (101 2±10 8,99 5±22 3, 91 4±23 5 vs 122 1±22 9, r =0 998) and MCD (0 69±0 31, 0 63±0 21,0 59±0 21 vs 0 78±0 1, P <0 05, P <0 01). CONCLUSION MN9202 decrease RBC cytosolic free Ca 2+ concentration and inhibit membrane lipid peroxidation, and these effects are related with improvement of RBC deformation.
出处
《中国药理学通报》
CSCD
北大核心
2000年第4期406-408,共3页
Chinese Pharmacological Bulletin
基金
国家科委医药创新博士基金资助项目!No 94 B 0 4
关键词
MN9202
血栓形成
红细胞变形
SOD
钙拮抗剂
calcium antagonist
RBC
cytosolic free Ca^(2+)
Ca MgATPase
MDA
SOD
RBC deformation
