辛伐他汀对大鼠冠脉微栓塞后微小血管再生影响的实验研究

Effect of simvastatin on micro-vascular angiogenesis after coronary microembolization in rats

目的探讨辛伐他汀干预对冠脉微栓塞(CME)后心肌微小血管保护与微小血管再生的影响及可能机制。方法自心尖部注入大鼠自体血栓微粒造成心肌内微小血管栓塞,建立冠脉微栓塞模型。40只大鼠随机分成5组:对照组(C组)、假手术组(sham组)、冠脉微栓塞模型组(M组)、辛伐他汀干预组(ST组)及辛伐他汀+N-硝酸-L-精氨酸甲酯(L-NAME)干预组(STN组)。28 d后使用Ⅷ因子染色评定单位面积心肌微小血管的密度,免疫荧光检测单位面积心肌微小血管的数量。采用硝酸还原比色法测定心肌组织中NO含量。结果术后28 d,辛伐他汀组与微栓塞组比较,微小血管密度及微小血管数量均显著增加(均P<0.01);辛伐他汀+L-NAME组与辛伐他汀组比较,微小血管密度及微小血管数量均显著减少(P<0.01)。微栓塞组与sham组比较,NO含量显著下降(P<0.05);辛伐他汀组与微栓塞组比较,NO含量显著性增加(P<0.01);辛伐他汀+L-NAME组与辛伐他汀组比较,NO含量显著下降(P<0.01)。结论辛伐他汀可增加冠脉微栓塞后心肌内微小血管密度和新生微小血管数量,而这种作用可能是通过一氧化氮(NO)介导的。

Objective To explore the effect of simvastatin on the micro-vascular angiogenesis in myocardium in a rat model with coronary microembolization（CME） and its possible mechanisms.Methods A rat model of CME was established by injecting a suspension of autologous microthrombotic particles into left ventricle.Forty rats were randomly divided into 5 groups（n =8 in each group）：control group,sham-operation group,model group,simvastatin group and simvastatin ＋ L-NAME group.The density of micro-vessel was detected by Factor-Ⅷ-staining and the number of micro-vessel was counted by immunofluorescence.Colorimetry with nitrate reduction was used to measure the concentration of nitric oxide（NO） in the myocardial tissues.Results Compared with model group,the concentration of NO,the density of micro-vessel and the number of micro-vessel significantly increased in simvastatin group at 28 d after CME （P＜ 0.01）.Compared with simvastatin group,the concentration of NO,the density of micro-vessel and the number of micro-vessel significantly decreased in simvastatin ＋ L-NAME group at 28 d after CME （P ＜ 0.01）.Conclusion Simvastatin may increase the density and number of micro-vessel in myocardium and NO may partially mediate the micro-vessel protection and angiogenesis.