摘要
目的:观察兔心肌梗死模型中不同剂量阿托伐他汀对循环内皮祖细胞数量和心肌血管新生的影响。方法:建立新西兰大耳白兔心肌梗死模型后,动物随机分成生理盐水[5 mg/(kg.d)]对照组、阿托伐他汀常规剂量组[5 mg/(kg.d)]和阿托伐他汀强化剂量组[20 mg/(kg.d)],灌胃给药8周。取外周血分离单核细胞进行内皮祖细胞培养1周后,鉴定FITC-UEA-Ⅰ和Di1-acLDL双染色阳性细胞为正在分化的内皮祖细胞,在倒置荧光显微镜下计数。以羊抗兔CD31抗体对心肌微血管进行免疫组化染色,显微镜下计数心肌新生的微血管数,取血管数平均值为微血管密度。结果:与对照组和强化剂量组比较,阿托伐他汀常规剂量组明显增加外周血中内皮祖细胞的数量,高倍视野中对照组、强化剂量组和常规剂量组内皮祖细胞数分别为(211.17±18.65)、(240.29±44.37)和(321.44±30.27)个(P<0.05),强化剂量组与对照组比较差异无统计学意义。常规剂量组心肌微血管密度较对照组和强化剂量组明显升高,高倍视野中3组微血管数分别为(16.78±3.50)、(11.17±2.64)和(12.86±3.72)(P<0.05)。强化剂量组与对照组比较虽有升高趋势,但差异无统计学意义。结论:常规剂量阿托伐他汀可增加心肌梗死后兔外周循环血中内皮祖细胞数量,促进缺血坏死心肌内新生血管的形成,这些作用可能独立于其降脂效应。
Objective： To investigate the effect of atorvastain on the number of circulating endothelial progenitor cells and myocardial neovascularization in rabbits with acute myocardial infarction（AMI）.Methods：Rabbits with AMI induced by permanent ligation of the left anterior descending coronary artery were randomized into 3 groups：control group [normal saline 5 ml/（kg·d）],atorvastain normal dosage group [5 ml/（kg·d）] and atorvastain high dosage group [20 ml/（kg·d）].Rabbits in each group were gavaged with drug or saline for 8 weeks from the 1st day after establishment of AMI model.Mononuclear cells isolated from peripheral blood were cultured for 1 week.The cells double stained by FITC-UEA-Ⅰ and Di1-acLDL were characterized as differentiating endothelial progenitor cells and were counted under fluorescent inverted microscope.The myocardium was stained by goat-anti-rabbit CD31 antibody and the number of myocardial microvessel was counted under ordinary optical microscope.The average value of microvessel number was regarded as microvessel density（MVD）.Results：The number of endothelial progenitor cells in atorvastatin normal dosage group was significantly higher than that in control and high dosage groups：（321.44±30.27） cells vs（211.17±18.65） cells and（240.29±44.37） cells（P〈0.05）.There was no significant difference between control group and high dosage group.MVD in normal dosage group was significantly higher than that in control and high dosage groups（P〈0.05）.The numbers of microvessels in each high power field were（16.78±3.50） vs（11.17±2.64） and（12.86±3.72）,respectively.Although MVD in high dosage group was higher than that in control group,there was no significant difference.Conclusion：Atorvastatin can increase the number of endothelial progenitor cells circulating in peripheral blood of rabbits with AMI and promote myocardial neovascularization.Moreover,these effects may be independent of its cholesterol-lowering effect.
出处
《药学服务与研究》
CAS
CSCD
2010年第2期115-119,共5页
Pharmaceutical Care and Research
关键词
阿托伐他汀
心肌梗死
循环内皮祖细胞
新生血管化
生理性
atorvastain
myocardial infarction
circulating endothelial progenitor cells
neovascularization,physiologic
