摘要
目的观察大鼠急性心肌梗死后不同时间点caspase-12表达的变化,探讨内质网应激途径在心肌梗死后心肌细胞凋亡中的作用。方法 80只雄性Wistar大鼠随机分为假手术组(n=40)和心肌梗死组(n=40),每组再进一步分为1、6、12、24h亚组(n=10)。心肌梗死组结扎大鼠左冠状动脉前降支复制大鼠急性心肌梗死模型,假手术组只穿线不结扎。分别于结扎后1、6、12、24h采用TUNEL法检测心肌细胞凋亡,Western blotting检测caspase-12的表达。结果 TUNEL结果显示:假手术1、6、12、24h亚组间心肌细胞凋亡指数(AI)(分别为1.40%±0.96%、1.47%±0.85%、1.56%±0.93%、1.72%±1.13%)无统计学差异(P>0.05),心肌梗死后1、6、12、24h亚组AI(分别为6.20%±2.15%、10.87%±2.84%、20.82%±3.80%、45.44%±9.22%)与假手术组比较明显升高,且心肌梗死各亚组间差异均有统计学意义(P<0.05)。Western blotting结果显示:假手术1、6、12、24h亚组caspase-12蛋白的表达(分别为0.056±0.011、0.063±0.013、0.068±0.013、0.075±0.017)无统计学差异(P>0.05),心肌梗死后1、6、12、24h亚组caspase-12蛋白的表达(分别为0.085±0.008、0.116±0.004、0.150±0.013、0.219±0.018)与假手术组比较均明显升高,且随心肌梗死延长表达逐渐增加(P<0.05)。Caspase-12表达与细胞凋亡变化规律一致。结论心肌梗死后凋亡细胞数和caspase-12蛋白表达逐渐增强,提示内质网通路可能参与了心肌梗死后心肌细胞凋亡的调控。
Objective To observe the expression of caspase-12 in rat acute myocardial infarction model,and explore the role of endoplasmic reticulum stress in cardiomyocyte apoptosis after myocardial infarction.Methods A total of 80 male Wistar rats were randomly divided into sham operation group（S group） and myocardial infarction group（MI group）.Animals in each group were then randomly reassigned into 1h,6h,12h and 24h subgroups according to the observation time（10 rats for each subgroup）.Models of myocardial infarction were reproduced by ligation of the left anterior descending branch of the coronary artery,and the rats in S group underwent the same procedure except for the ligation of the coronary artery.Cardiomyocyte apoptosis was observed with in situ terminal deoxynucleotidyl transferase（TdT）-mediated dUTP-nick end labeling（TUNEL）,and the expression of caspase-12 was detected by Western blot at different time points（1,6,12 and 24h after myocardial infarction）.Results Compared with the animals in S group,cardiomyocyte apoptosis index（AI） was significantly increased in MI group（P〈0.05）.The AI of each MI subgroup increased along with the time of myocardial infarction（P〈0.05）.Western blotting showed that the expression of caspase-12 in MI group was enhanced as myocardial infarction was prolonged.These results indicated the consistency in the changing trend of caspase-12 with cell apoptosis.Conclusions The expression of caspase-12 is gradually increased after myocardial infarction,which shows a consistency with the myocardial apoptosis,implying that caspase-12 may induce endoplasmic reticulum stress in cardiomyocyte apoptosis.It might suggest that endoplasmic reticulum stress would play an important role in the course of cardiomyocyte apoptosis induced by myocardial infarction.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2011年第3期257-259,共3页
Medical Journal of Chinese People's Liberation Army
基金
国家科技部国际科技合作重大专项课题(2006DFB32210)
