摘要
目的观察不同剂量的阿托伐他汀对心肌损伤后大鼠骨髓和外周血内皮祖细胞动员及血管内皮功能的影响。方法S-D大鼠背部皮肤多点注射异丙肾上腺素(5mg/kg)制造心肌损伤模型后,随机分为生理盐水对照组和不同剂量的阿托伐他汀组[5、10、20、40及80mg/(kg.d)]。4周后,流式细胞仪检测大鼠外周血CD34+和血管内皮生长因子受体2+双阳性细胞数。骨髓和外周血单个核细胞于M199培养基培养,FITC标记的异凝集素和DiI标记的乙酰化低密度脂蛋白染色双阳性细胞为正在分化的内皮祖细胞,倒置荧光显微镜计数3个随机高倍视野数。阿托伐他汀灌胃3天后测定血清一氧化氮浓度。结果阿托伐他汀各剂量组骨髓培养内皮祖细胞均较对照组明显增加(P<0.05),其中40mg/(kg.d)组内皮祖细胞数量最多,较对照组增加了2.4倍(P<0.05),80mg/(kg.d)组与40mg/(kg.d)组比较稍有下降,但无统计学差异;阿托伐他汀组外周血培养内皮祖细胞较对照组明显增加,40mg/(kg.d)组增加最明显(P<0.05);心肌损伤后外周血CD34+/血管内皮生长因子受体2+细胞较损伤前增加(P<0.05),其中80mg/(kg.d)组最明显,较对照组增加了4.18倍(P<0.05),40mg/(kg.d)组与80mg/(kg.d)组无统计学差异;阿托伐他汀各剂量组血清一氧化氮浓度较对照组明显增加,其中80mg/(kg.d)组增加最明显,并随剂量增加一氧化氮浓度增加。结论阿托伐他汀具有显著的剂量依赖性骨髓动员、促进外周血中内皮祖细胞迁移、改善血管内皮功能的作用。
Aim To investigate whether atorvastatin dose-dependently affects endothelial progenitor cells （EPC） mobilization from peripheral blood, EPC numbers in bone marrow culture in vitro and endothelial function after myocardial injury rats. Methods Rats with myocardial injury, induced by isoprenaline, were randomized to treatment groups with vehicle or atorvastatin [5, 10, 20, 40 and 80 mg/（kg·d）] for 4 weeks starting on one day after Myocardial injury. Putative precursor populations [CD34^＋/vascular endothelial growth factor receptor 2 （VEGFR-2）^＋ haematopoietic stem cells] were measured by flow cytometric analysis. Total mononuclear cells （ MNC ） were isolated from peripheral blood by Ficoll density gradient centrifugation, and the cells were plated on gelatin coated culture dishes. Double-stained cells for both FFTC BS-1 lectin and acLDL-DiI were counted as EPC in at least 3 randomly selected HPF. Serum concentration of nitric oxide （NO） was measured after atorvastatin use. Results Atorvastatin increased EPC numbers both in bone marrow and peripheral blood culture in vitro, maximum at 40 mg/（kg·d） （ P 〈 0.05）. EPC numbers at the dose of 80 mg/（kg·d） were slightly reduced comparing with 40 mg/（kg·d）, but there was no statistical difference; circulating EPC （double positive CD34^＋/VEGFR-2^＋） were significantly elevated after myocardial injury （ P 〈 0.05） ; EPC mobilization was markedly further augmented by atorvastatin treatment, maximum at 80 mg/（kg·d） （4.18-fold increase, P 〈 0.05）. There was no statistical difference between 40 mg/（ kg· d） and 80 mg/（kg·d）; Atorvastatin induced a dose-dependant increase in serum concentration of NO generation, with maximal effect at 80 mg/（ kg·d）. Conclusions Atorvastatin dose-dependently improve EPC mobilization, EPC numbers in vitro culture, and endothelial function.
出处
《中国动脉硬化杂志》
CAS
CSCD
2007年第4期277-280,共4页
Chinese Journal of Arteriosclerosis
关键词
内科学
阿托伐他汀
内皮祖细胞
血管内皮功能
心肌损伤
血管内皮生长因子受体2
Atorvastatin
Endothelial Progenitor Cells
Vascular Endothelial Function
Myocardial Injury
Vascular Endothelial Growth Factor Receptor-2
