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 - 3-甲酯 - 5 -正戊酯(MN92 0 2 )在 L-甲状腺素 (L- thyroxine,L- Thy)引起大鼠心肌肥厚时对心脏指数 ,心肌超微结构及心肌组织超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH- PX)活性和丙二醛(MDA)含量的影响 .方法 连续 12 d ip L- Thy0 .5 mg·kg- 1 · d- 1 复制大鼠心肌肥厚模型 ,实验组 ip MN92 0 2 0 .4mg· kg- 1· d- 1 ,2 mg·kg- 1· d- 1 ,10 mg· kg- 1· d- 1 ,阳性对照组 ip卡托普利 2 5 mg· kg- 1 · d- 1 ,模型组、对照组给予等量溶剂 ,于给药后的第 13日处死大鼠 ,检测心脏指数 ,电镜观察心肌组织的超微结构变化 ,化学比色法测定心肌匀浆中 SOD、GSH- PX活性和 MDA含量 .结果 在注射 L- Thy12 d后 ,与对照组相比 ,MN92 0 2能明显降低心脏指数 ,减轻心肌组织超微结构的病理改变 ,显著提高大鼠心肌中 SOD和 GSH- PX活性 ,并减少 MDA的生成 ,尤以中、高剂量为佳 (P<0 .0 5 ,P<0 .0 1) .结论 MN92 0 2能抑制 L - Thy所引起的心肌肥厚 ,对心肌组织具有保护作用 ,该作用与阻止 Ca2 +内流 ,防止钙超载 ,提高氧自由基清除活性 。
AIM To investigate the effect of methyl pentyl 1,4 dihydro 2,6 dimethyl 4 (3 nitrophenyl) 3,5 pyridinedicarboxylate (MN9202),a dihydropyridine calcium antagonist, on cardiac indexes,ultrastructure, superoxide dismatase (SOD),glutathione peroxidase (GSH PX) activity and malondialdehyde (MDA) concentration in cardiac hypertrophy induced by L thyroxine (L Thy) in rats. METHODS cardiac hypertophic model of rats was induced by a continued administration of L Thy 0.5 mg·kg -1 ip once daily for 12 d. Three doses (0.4, 2, 10 mg·kg -1 ) of MN9202 or captopril (25 mg·kg -1 , positive group), vehicle (model group or control group) were injected by ip before 8 h L Thy injection; cardiac indexes were examined; the change of myocardial ultrastructure were observed with electron microscope; the activity of SOD, GSH PX and concentration of MDA were measured by colorimetric analysis. RESULTS by a continued ip L Thy for 12 d, MN9202 could obviously reduce the cardiac indexes, improve the development of ultrastructural pathological change at myocardium and significently increased the SOD,GSH PX activity and reduce the production of MDA in rats, especially in middle dose and high dose ( P <0.05, P <0.01). CONCLUSION MN9202 can inhibit cardiac hypertrophy induced by L Thy and protect cardiac tissue from injury, which may be related to blocking intracellular Ca 2+ influx, reduceing calcium accumulation and increasing the activity of clearence enzyme of free radical and inhibiting lipid peroxidation
出处
《第四军医大学学报》
2000年第6期S141-S144,共4页
Journal of the Fourth Military Medical University
关键词
NM9002
钙拮抗剂
心肌肥厚
甲状腺素
超微结构
dihydropyridines
calcium antagonist
myocardium hypertrophy
thyroxine
oxygen free radicals
ultrastructure
