阿司匹林与培哚普利合用对兔动脉粥样硬化模型血中PGI_2,TXA_2,NE及心功能的影响

Effect of aspirin combined with perindopril on prostacyclin, thromboxone A_2, and norepinephrine in the blood of arteriosclerosis rabbit models and the cardiac function

目的 :探讨小剂量阿司匹林 (ASA)和培哚普利 (PER)单用或合用对兔动脉粥样硬化模型血中前列环素(PGI2 )、血栓素A2 (TXA2 )和去甲肾上腺素 (NE)浓度的变化 ,以及心功能 (HR ,LVEDP ,LVSP ,±dp/dtmax)和血脂的影响 .。方法 :将 6 0只成年新西兰白兔随机分成 5组 ,高脂饲料喂养制备动脉粥样硬化模型 ,于连续投药八周前后分别经颈总动脉插管进行心功能测定和采血 ,放射免疫法检测PGI2 和TXA2 ;高效液相色谱法检测NE ;酶法及沉淀法检测血脂。结果 :病理学及血脂检查证实造模成功。对兔动脉粥样硬化模型 ,ASA与PER合用时自身前后比较 ,PGI2 /TXA2 值显著上升 (P <0 .0 1) ,血清NE浓度明显下降 (P <0 .0 1) ,同时LVEDP(P <0 .0 1)和HR(P <0 .0 1)下降 ,LVSP上升 (P <0 .0 1)。结论 :对兔动脉粥样硬化模型 ,ASA和PER合用时 ,PGI2 /TXA2 值上升 ,血清NE浓度下降 ,心率减慢 ,心脏舒缩功能改善 。

Objective To explore the interactive effect of low dosage aspirin (ASA)combined with perindopril (PER) on prostacyclin (PGI 2), thromboxone A 2 (TXA 2), and norepinephrine (NE) in the blood of arteriosclerosis rabbit models and the cardiac function. Methods Sixty adult New Zealand rabbits were randomly distributed into 5 groups with 12 rabbits in each group. One group was fed with standard fodder; the others were fed with high lipoid diet (1% cholesterol content). Before and after 8 weeks′ administration consecutively, LVEDP, LVSP, HR, ±dp/dtmax, plasma PGI 2 and TXA 2, serum NE, total cholesterol (TC), low density lipoprotein cholesterol (LDL ch), high density lipoprotein cholesterol (HDL ch) and triglycerides (TG) were evaluated. Results TG, TC, LDL ch and pathological results confirmed arteriosclerosis rabbit models successfully. ASA combined with PER led to a significant increase in PGI 2/TXA 2 (P<0.01) together with a significant decrease in the NE levels (P<0.01) in the rabbits′ blood, and then improved the cardiac output, i.e. increased LVSP (P<0.01), and decreased the heart rate (P<0.01) and LVEDP (P<0.01) to a greater extent in the arteriosclerosis rabbit models. Conclusion The ratio of PGI 2 to TXA 2 increased, and the NE levels decreased significantly; meanwhile, the heart rate decreased and the cardiac function improved during the administration of aspirin combined with perindopril in arteriosclerosis rabbit models. The results suggest that there is a synergism action between low dosage aspirin and ACE inhibitors due to increased PGI 2/TXA 2 and decreased NE levels.