MN9202对血栓形成大鼠红细胞Ca^(2+)浓度、脂质过氧化的影响及其与增强红细胞变形性关系的探讨  

Effects of methyl pentyl 1,4 dihydro 2,6 dimethyl 4 (3 nitrophenyl) 3,5 pyridinedicarboxylate(MN9202) on [Ca^(2+) ] i transport, lipid peroxidation and its relationship with the deformation of RBC in thrombosis rats induced by ca

作　　者：王莉莉[1] 梅其炳[1] 赵德化[1] 武丽华[2] 田巧莲[1] 李景峰[1] 

机构地区：[1]第四军医大学药理学教研室,西安710032 [2]第四军医大学中心实验室,西安710032

出　　处：《中国药理学通报》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

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.

关 键 词：MN9202 血栓形成 红细胞变形 SOD 钙拮抗剂 

分 类 号：R972.4[医药卫生—药品]