新型AT_1受体拮抗剂Ⅰb对异丙肾上腺素诱发大鼠心肌肥厚的作用

Effects of a new angiotensin type 1 receptor antagonist Ⅰb on isoproterenol-induced cardiac hypertrophy in rats

目的:考察AT1受体拮抗剂Ⅰb对异丙肾上腺素诱发大鼠心肌肥厚的作用。方法:异丙肾上腺素连续每日以20,10和5mg/kg的剂量递减皮下注射,再以3mg/kg的剂量维持皮下注射7d,第7天开始尾静脉注射化合物Ⅰb。观察心脏重量系数、心肌组织丙二醛(MDA)含量、心肌组织超氧化物歧化酶(SOD)活力、血清乳酸脱氢酶(LDH)活力以及组织学变化。结果:3mg/kg组可以逆转异丙肾上腺素所致大鼠心肌肥厚,心脏重量系数明显改善,心肌组织MDA含量降低,SOD活力升高,血清LDH活力下降。电镜结果显示心肌组织线粒体和肌纤维结构改善。结论:化合物Ⅰb可抑制异丙肾上腺素引起的大鼠心肌肥厚,明显改善心肌肥厚的各种指征。

Aim： To study the effects of compound Ⅰ b as a new angiotensin type 1 receptor antagonist on isoproterenolinduced cardiac hypertrophy in rats. Methods： Cardiac hypertrophy in rats was induced by subcutaneous administration of isoproterenol in which the dosage schedule was set to 20 mg/kg in the 1st day, 10 mg/kg in the 2nd day, 5 mg/kg in the 3rd day, and 3mg/kg in the following consecutive seven days. Compound Ⅰ b was given to rats via tail vein in the 7th day. Cardiac mass index, malondialdehyde（MDA） content of cardiac muscle, the activity of cardiac muscle superoxide dismutase （SOD）and the lactate dehydrogenase （LDH） released to the serum were observed. Results： It was shown that at a dose of 3mg/kg Ⅰb improved the cardiac mass index, significantly decrease MDA content of the cardiac muscle, increased the activity of cardiac muscle SOD, and significantly decreased the LDH released to the serum. Electron microscope showed that Ib improved the structure of cardiac muscle fiber and mitochondria. Cardiac muscle fiber lined up in order, and Z line was clear. Conclusion： Compound Ⅰ b was shown to be effective against isoproterenol-induced cardiac hypertrophy in rats.