阿托伐他汀预处理对大鼠心肌缺血-再灌注损伤的保护作用机制研究

Mechanism of the protective effect of atorvastatin pretreatment on myocardial ischemia-reperfusion injury in rats

目的 阿托伐他汀具有多重心肌保护作用,但其机制尚不明确,本文应用大鼠心肌缺血-再灌注损伤（MIRI）模型研究短期阿托伐他汀预处理的心肌保护作用,并对其与血浆内皮素（ET）、血栓素A2（TXA2）、前列环素（PGI2）的关系进行初步探讨.方法 将80只雄性SD大鼠随机等分为4组：假手术组（A组,生理盐水5 mL/d）、MIRI组（B组,生理盐水5 mL/d）、阿托伐他汀标准剂量预处理组[C组,阿托伐他汀20 mg/（kg·d）]和阿托伐他汀强化剂量预处理组[D组,阿托伐他汀40 mg/（kg·d）].灌胃3 d后,第4天制作大鼠在体MIRI模型,结扎左冠状动脉前降支30 min,再灌注120 min后,用放射免疫分析法测定血浆ET、TXA2、PGI2含量.结果 与A组比较,B组血浆ET和TXA2水平升高、PGI2水平及PGI2/TXA2比值降低（P〈0.05）;与B组比较,C组ET和TXA2水平降低、PGI2水平及PGI2/TXA2比值升高（P〈0.05）;与C组比较,D组ET和TXA2水平降低、PGI2水平及PGI2/TXA2比值升高更为明显（P〉0.05）.结论 在大鼠MIRI中,阿托伐他汀预处理可促进PGI2生成,扩张血管,削弱内皮因子的收缩作用,降低ET含量,调节PGI2/TXA2平衡,改善微循环,从而发挥心肌保护作用.

Objective Atorvastatin has multiple myocardial protective effects, but its mechanism is not clear. In this study, we explored the short - term myocardial protective effects of atorvastatin in the rat model of myocardial ischemia - reperfusion injury （ MIRI）, and discussed the relationship with the plasma endothelin （ ET）, thromboxane A2 （ TXA2 ） and prostacyclin （ PGI2 ）. Methods 80 male SD rats were randomly divided into 4 groups： sham operation group （A group, normal saline 5 mL/d）, ischemia reperfusion group （B group, 5 mL/d normal saline）, standard dose of atorvastatin pretreatment group [ C group, atorvastatin 20 mg/（ kg. d） ] and intensive dose of atorvastatin pretreatment group [ D group, atorvastatin 40 mg/（ kg＂ d ）]. Atorvastatin was administered intragastrically for 3 days, and then the rats were access to myocardial ischemia - reperfusion surgery. The left anterior descending coronary artery was ligated for 30 min, and re - reperfused for 120 rain. The concentration of plasma endothelin （ ET）, thromboxane A2 （ TXA2 ） and prostacyclin （ PGI2 ） were measured by radioimmunoassay. Results Compared with group A, plasma ET and TXA2 levels were increased, PGI2 level was decreased, the ratio of PGIJTXA2 was decreased in group B （P 〈0.05） ; Compared with group B, ET and TXA2 levels were decreased, PGI2 level was increased, the ratio of PGIz/TXA2 was increased in group C （ P 〈 0.05 ） Compared with group C, ET and TXA2 levels were decreased, the level of PG[2 and the ratio of PGI2/TXA2 were significantly increased in group D （P 〈 0. 05）. Conclusion In MIRI rat model, atorvastatin pretreatment can promote the formation of PGI2, decrease the content of ET, regulate the balance of PGIz/TXA2, improve microcirculation, then play a role in myocardial protection.