目的对比瑞苏伐他汀单次及多次给药对猪心肌缺血再灌注后无再流及血管内皮结构和功能的影响。方法19只中华小型猪分为安慰剂组、瑞苏伐他汀单次及多次给药组。开胸冠状动脉结扎1.5h,松解3h制备急性心肌梗死再灌注模型。术中监测动脉血压、心室压、心率及冠脉血流量。手术结束前经左房、室分别注射硫磺素s、伊文思蓝染料鉴别无再流、缺血区域。心肌组织以红四氮唑染色,用面积求积法测定心肌的缺血、梗死及无再流面积。以比色法测定再流区及无再流区心肌组织中的固有型一氧化氮合酶(cNOS)活性,并以免疫印迹法测定血管内皮钙黏附分子(VE—cadherin)含量。结果各组缺血前血压和心率的乘积无统计学差异;再灌注180min时瑞苏伐他汀多次给药组冠脉血流量明显高于安慰剂组和单次给药组(P〈0.05);瑞苏伐他汀多次给药组梗死区面积与心肌缺血面积的百分比值、无再流面积与心肌缺血面积的百分比值、心肌再流区、无再流区cNOS活性与安慰剂组比较均有统计学差异(P〈0.05)。瑞苏伐他汀多次给药组无再流区VE-cadherin含量明显高于安慰剂和单次给药组。结论在急性心肌梗死急性期,瑞苏伐他汀可以减轻心肌缺血再灌注损伤,但给药方式会影响其疗效。
Objective To compare single and repeated administration protocol with rosuvastatin on no reflow and endothelial functional and structural integrity in a mini-swine model of acute infarction and reperfnsion. Methods 19 openchest pigs were randomized into three groups: 7 in placebo, 7 in rosuvastatin pretreatment for 4 days (R4) and 5 in rosuvastatin for single pretreatment ( R1 ) group. The model was created through 90 min ligation of the left anterior descending coronary artery (LAD) followed by 180 min of reperfusion. Results Compared with placebo, R4 increased the local LAD blood flow at the 180 min of reperfnsion and limited the infarct and no reflow size (P 〈0.05 respectively). R4 increased the cNOS activity in reflow region (P 〈 0.05 ). The level of VE-cadherin was also preserved in the no reflow region of R4. R4 decreased the level of serum total cholesterol and low density lipoprotein ( P 〈 0.05 ). Whereas R1 pretreatment failed to take effects as R4 did. Condusions Rosuvastatin pretreatment reduces the size of no reflow and preserves endothelial functional and structural integrity after myocardial ischemia and reperfusion. The effect is dependent on the method of pretreatment.