氟伐他汀动员内皮祖细胞促进大鼠梗死心肌血管新生的作用

Endothelial progenitor cells mobilization by fluvastatin promoting myocardial neovascularization in rats with acute myocardial infarction

目的观察氟伐他汀动员急性心肌梗死（AMI）大鼠内皮祖细胞（EPCs），促进梗死心肌血管新生，减小梗死面积的效果。方法①成年Wistar大鼠左前降支结扎造模，随机分为空白组（A组）、假手术组（B组）、AMI组（C组）和氟伐他汀治疗AMI组（D组）。②流式细胞技术检测不同时段大鼠外周静脉血EPC动态变化。③4周末处死大鼠，心肌切片Masson染色，左室心肌正中线弧长方法计算梗死面积。④CD31单克隆抗体免疫组化法标记心肌新生血管内皮细胞并计算各组梗死、梗死周边及非梗死区新生血管数。结果①造模后第7天D组EPCs（37．13±3．44／2×10^5MNCs）显著高于A组（19．88±4．91／2×10^5MNCs）、B组（22．33±5．43／2×10^5MNCs）和C组（26．56±3．17／2×10^5MNCs），差异具有统计学意义（P〈0．05）；C组较A组有少量增加（P〈0．05），B组较A组无明显升高（P〉0．05），B组和c组差异无统计学意义（P〉0．05）。造模后第14天D组EPCs（45．5-±4．99／2×10^5MNCs）同样显著高于A组（17．25±7．17／2×10^5MNCs）、B组（22．78±2．91／2×10^5MNCs）和C组（26．88±3．76／2×10^5MNCs）（P〈0．05）；B组和C组较A组有少量增加（P〈0．05），B组和C组差异无统计学意义（P〉0．05）。第7天和第14天各组变化比较，A、B、C三组EPCs变化无统计学意义（P〉0．05），D组则明显增加（P〈0．05）。②D组梗死区新生血管计数（10．75±1．61／mm。）明显多于C组（5．09±2．33／mm。）（P〈0．01），梗死周边区新生血管计数D组（17．53±2．35／mm^2）同样明显多于C组（8．55±2．40／mm^2）（P〈0．01）。③D组梗死面积[（31．41±2．59）％]小于C组[（35．67±5．22）％]（P〈0．01）。结论①氟伐他汀能动员急性心肌梗死大鼠内皮祖细胞进入外周血循环，使其数量增加并促进梗死周边区血管新生。②心肌梗死后大鼠应用氟伐他汀可以限制梗死面积。

Objective To observe the effect of fluvastatin on endothelial progenitor cells （EPCs） mobi- lization in Wistar rats with acute myocardial infarction （AMI）, and the consequences of myocardial neovasculariza-tion and myocardial infarction size restriction. Methods （1） Adult Wistar rats were randomly divided into 4 groups： normal control group （A）, sham operation group（B）, AMI group（C）, AMI treated with Fluvastatin （D）. （2）Peripheral venous blood were drew at day 7 and 14 after AMI to detect the EPCs by flow cytometry analysis. （3） The infarct size was calculated by the method of measuring left ventricular midline infarct arc length. （4）Immunohis-tochemical stain of anti-rat CD31 monoclonal antibody was used to detect the density of myocardial neovasculariza-tion in myocardial infarction region, periinfarction region and non infarction region. Results （1）At 7th days after AMI, the number of EPCs in group D （37.13±3.44/2×10^5 MNCs） increased significantly than those in group A （19.88±4.91/2×10^5 MNCs）, group B （22.33±5.43/2×10^5 MNCs） and group C （26.56±3.17/2×10^5 MNCs）（P〈 0.05）, and the number of EPCs in group C increased slightly than those in group A （P〈0.05）, the number of EPCs in group B didn＇t increased than those in group A （P〉0.05）, there were no significant statistical difference among group B and C （P〉O.05）. And 14th days after AMI, the number of EPCs in group D （45.5±4.99/2×10^5 MNCs） increased also significantly than those in group A（17.25±7.17/2×10^5 MNCs）, group B（22.78±2.91/2×10^5 MNCs） and group C （26.88±3.76/2±105 MNCs）（P〈0.05）, and the number of EPCs in group C and group B in-creased slightly than those in group A（P〈0.05 ）, there were no significant statistical difference among group B and C （P〉0.05）. Between the numbers of EPCs at day 7 and day 14, there were no significant statistical diference in group A, B and C （P〉0.05）, but there were significant increasing in group D（P〈0.05）. （2）The capillary densitiy in myocardial infarction were higher in group D （10.75±1.61/mm^2） than in group C（5.09±2.33/mm^2） （P〈0.01）, and in periinfaction region, the capillary densitiy were also higher in group D （17.53±2.35/mm^2） than in group C （8.55±2.40/mm^2） （P〈0.01）. （3） The infarct size in group D （31.41±2.59）% was smaller than that in group C （35.67±5.22）%（P〈0.01）. Conclusion （1）Fluvastatin could mobilize EPCs into peripheral circulation and pro-mote myocardial neovaseularization in rats with AMI. （2）Fluvastatin could restrict infarct size.