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(MN9202)抗实验性血栓形成作用  

Effect of methyl pentyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (MN9202) on experimental thrombosis

作　　者：王莉莉[1,2] 梅其炳[1,2] 赵德化[1,2] 田巧莲[1,2] 张周良 

机构地区：[1]第四军医大学药理学教研室 [2]第四军医大学唐都医院检验科

出　　处：《中国药学杂志》1998年第5期282-285,共4页Chinese Pharmaceutical Journal

基　　金：国家科委医药创新博士基金

摘　　要：目的：探讨新的二氢吡啶钙通道阻滞剂ＭＮ９２０２对实验性血栓形成的影响及其作用机制。方法：采用ｉｖ胶原肾上腺素或ｓｃ角叉菜胶，分别复制小鼠肺血栓和尾血栓模型。观察ＭＮ９２０２对实验性肺血栓小鼠死亡率，血栓黑尾形成率及微循环的影响。用凝血酶ＡＤＰ肾上腺素复合诱导剂，复制大鼠脑血栓模型，观察ＭＮ９２０２对大鼠脑血栓损伤的预防作用。结果：ＭＮ９２０２４ｍｇ·ｋｇ－１ｉｐ，能明显降低胶原肾上腺素引起的小鼠死亡率（３０ｖｓ８４Ｐ＜０．０１）；６ｍｇ·ｋｇ－１ｉｇ，对凝血酶诱导的大鼠脑血栓损伤具有保护作用（０．０６９±０．０６８ｖｓ０．１１０±０．０１３，Ｐ＜０．０１）；０．０４，０．４ｍｇ·ｋｇ－１能降低角叉菜胶诱导的血栓黑尾发生率（３０，１０ｖｓ９０，Ｐ＜０．０５；Ｐ＜０．０１），明显减轻微血管内皮的渗出，抑制血小板聚集和ＲＢＣ聚集，改善微血管血流速度。结论：ＭＮ９２０２具有对抗血小板聚集诱导剂及角叉菜胶引起的血栓形成作用。其机制可能与其抑制ＲＢＣ、血小板聚集，保护血管内皮，舒张痉挛血管有关。OBJECTIVE: To investigate the effects of MN9202 on experimental thrombosis and its probable mechanism. METHODS: Male LACA mice were injected with collagen and adrenalin iv. or carrageenan sc. to induce plumonary thrombus or thrombus in tail. To observe the effects of MN9202 on mortality of plumonary thrombous, thrombosis in tail and microcirculation changed. SD rats of male, ig vehicle, asprin and MN9202 at dosage of 2, 6 mg·kg -1 , 1 h later, were treated with thrombin, ADP and adrenalin compound to make cerebral thrombus. We observed the effect of MN9202 on cerebral thrombosis. RESULTS: MN9202 at dosage of 4 mg·kg -1 reduced the mortality in plumonary thrombus (30 vs 84, P<0.01). 6 mg·kg -1 abated the extent of cerebral thrombosis (0.069±0.068 vs 0.110 ±0.013, P<0.01). The incidence of thrombosis in tail of mice induced by carrageenan was inhibited by MN9202 at dose of 0.04, 0.4 mg·kg -1 at 72 h (30, 10, vs 90, P<0.05 or P<0.01). At same time, microvascular penetrate was abated, RBC aggregation and white micro thrombosis were inhibited, the speed of microvascular flow was increased by MN9202 (0.04, 0.4, 4 mg·kg -1 ). CONCLUSION: MN9202 can prevent thrombosis induced by platelet aggregation stimulus and carrageenan. MN9202 inhibits RBC and platelet aggregation, prevents damage to vascular endothelia, and improves blood state.

关 键 词：二氢吡啶 血栓形成 药理学 钙通道阻滞剂 

分 类 号：R972[医药卫生—药品]