不同剂量阿托伐他汀干预对兔急性心肌梗死细胞凋亡的影响
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江苏省社会发展基金资助项目(BS2002009)


The Effect of Early Atorvastatin Therapy on Cardiomyocyte Apoptosis and its Primary Mechanisms in Rabbit's Acute Myocardial Infarction
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    目的探讨不同剂量阿托伐他汀提早干预治疗对兔急性心肌梗死细胞凋亡的影响。方法24只新西兰兔随机分为3组:对照组动物不予药物干预;低剂量组动物按体重给予0.5 mg/(kg.d)阿托伐他汀;高剂量组动物按体重给予5 mg/(kg.d)阿托伐他汀。药物干预3天后制作急性心肌梗死模型,检测心肌梗死及其边缘区细胞凋亡率并观察心肌Bax与Bcl-2表达。结果①梗死区及边缘区高剂量组细胞凋亡率明显低于对照组和低剂量组(梗死区为16%±5%比23%±7%和22%±5%,p<0.01;边缘区为15%±5%比26%±6%和25%±6%,p<0.01)。②梗死区及边缘区高剂量组Bcl-2表达高于对照组及低剂量组(梗死区为60±9比45±7和52±12,p<0.01;边缘区为61±13比48±9和52±11,p<0.05)。对照组与低剂量组无显著差异;③三组Bax表达均较高,组间无显著差异(梗死区为61±9比62±77和67±7,p<0.05;边缘区为57±6比59±10和60±8,p<0.05)。④Pearson线性相关分析梗死区与边缘区心肌细胞凋亡率与相应区域Bcl-2表达呈明显负相关(梗死区r=-0.672,p<0.01;边缘区r=-0.735,p<0.01)、与Bax表达无明显相关(梗死区r=0.133,P=0.559;边缘区r=0.177,P=0.409)。结论高剂量阿托伐他汀降低梗死区及其边缘区心肌细胞凋亡率,可能与Bcl-2表达增加有关。

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    Aim To investigate the effects of different doses of atorvastatin on cardiomyocyte apoptosis and primary mechanisms in acute myocardial infarction(AMI).MethodsTwenty-four New Zealand rabbits were randomly separated into three groups: the control group treated without lipid-lowering drugs,0.5 mg/(kg·d) and 5 mg/(kg·d) atorvastatin groups with 3 days of treatments.Then,the model of AMI was established by coronary-occluded method,and six hours later,cardiomyocyte apoptotic rate and the expression of Bax and Bcl-2 were detected.Results⑴Compared with control and 0.5 mg/(kg·d) atorvastatin groups,the apoptotic rate of infracted and border zone in 5 mg/(kg·d) atorvastatin group significantly lowered(16%±5% vs 23%±7% and 22%±5%,p<0.01;15%±5% vs 26%±6% and 25%±6%,p<0.01;respectively).⑵The content of Bax had no changes in every group(61±9 vs 62±77 and 67±7,p<0.05;57±6 vs 59±10 and 60±8,p<0.05),while that of Bcl-2 was evidently increased in 5 mg/(kg·d) atorvastatin group than the control group and 0.5 mg/(kg·d) atorvastatin group in infracted and border zone(60±9 vs 45±7 and 52±12,p<0.01;61±13 vs 48±9 and 52±11,p<0.05).⑶Correlation analysis indicated that there was a negative correlation between the rate of cardiomyocytes apoptosis and Bcl-2 expression(r=-0.672,p<0.01;r=-0.735,p<0.01),while there were no relation between the apoptotic rate and Bax(r=0.133,P=0.559;r=0.177,P=0.409)by Pearson correlation analysis.ConclusionsEarly intensive atorvastatin intervention may decrease cardiomyocyte apoptosis.Atorvastatin may be through pro-expression of Bcl-2 to resist apoptosis.Early intensive atorvastatin treatment may yield more significant benefits in AMI.

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夏勇,刘军,李东野,陈清枝.不同剂量阿托伐他汀干预对兔急性心肌梗死细胞凋亡的影响[J].中国动脉硬化杂志,2006,14(12):1016~1019.

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  • 收稿日期:2005-10-31
  • 最后修改日期:2006-12-12
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