阿托伐他汀对大鼠心肌急性缺血细胞凋亡及caspase-3基因表达影响

Effects of atorvastatin on the cardiomyocyte apoptosis and caspase-3 gene expression in rats with acute ischemia injury

目的:观察不同剂量阿托伐他汀对大鼠急性缺血心肌细胞凋亡及caspase-3基因表达的影响。方法:取雄性SD大鼠79只,随机分为模型组、阿托伐他汀高剂量组(20 mg/(kg.d))、中剂量组(10 mg/(kg.d))、低剂量组(2mg/(kg.d))和生理盐水对照组。除模型组只开胸外,其余大鼠术前连续灌胃3 d,第4天结扎冠状动脉左前降支造成急性心肌梗死模型。伊文氏蓝和TTC染色法确定缺血和梗死心肌范围。原位末端标记检测细胞凋亡,RT-PCR检测caspase-3 mRNA的表达。结果:与对照组比较,阿托伐他汀高?中剂量组可明显减少心肌梗死面积,明显减少心肌细胞凋亡和心肌内caspase-3 mRNA基因表达。不同剂量组间差异无统计学意义(P>0.05)。结论:高、中剂量阿托伐他汀可减少大鼠急性缺血心肌细胞损伤,与能减少心肌细胞凋亡及抑制caspase-3 mRNA基因表达有关。

Objective To investigate the effects of different dosages of atorvastatin on cardiomyocyte apoptosis and caspase-3 expression in acute ischemic cardiomyocyte in rats.Methods A total of 79 SD rats were randomly divided into 5 groups： sham group,control group（normal saline）,low-dose group（2 mg/kg atorvastatin pretreatment）,medium-dose group（10 mg/kg atorvastatin pretreatment）,and large-dose group（20 mg/kg atorvastatin pretreatment）.All groups except sham group were pretreated with normal saline for 3 days,and underwent coronary ligation of left anterior descending branch to establish acute myocardial infarction models on the fourth day,while sham group only received thoracotomy without coronary ligation.The infarct area were defined with Evans blue and TTC staining,the caspase-3 mRNA expression of myocardium was measured with reverse-transcriptase polymerase chain reaction（RT-PCR）,and cell apoptosis was detected with TUNEL staining.Results The infarct area,the caspase-3 mRNA expression and the apoptotic index decreased significantly in the large-and medium-dose groups than those in control group.There was no significant difference in the low-,medium-and large-dose groups（P0.05）.Conclusion Pretreatment with high-and medium-dose atorvastatin could protect acute ischemic cardiomyocytes,which may probably be associated with the reduction of the expression of caspase-3 mRNA in the myocardium and the apoptotic index.