Liu Q
Department of Emergency Medicine, People's Hospital of Zhengzhou, Zhengzhou, Henan Province, China.
Eur Rev Med Pharmacol Sci. 2014 Jul;18(13):1852-8.
To explore the heart protection effects by RNA interference of Caspase-3 on rat acute myocardial infarction (AMI).
45 SD rats were randomly divided into sham group, AMI group and Caspase-3-siRNA group. Animal model of AMI was established by ligation of anterior descending branch (LAD). Rats of sham operation group and AMI group were administered with lentivirus harboring empty vector into myocardial tissue. Rats of Caspase-3-siRNA group were administered with lentivirus harboring Caspase-3 RNA interference vector. After 72 hours, the heart function were evaluated by echocardiogram analysis. Then the rats were sacrificed and the myocardial tissue were collected. The expression level of Caspase-3 mRNA and protein in each group were analyzed by RT-PCR and Western blot, respectively. Moreover, the infarct size was analyzed by triphenyltetrazolium chloride (TTC) staining and the apoptosis index of myocardial cells were analyzed by TUNEL assay.
Compared with the sham operation group, the expression levels of Caspase-3 mRNA and protein were significantly upregulated (p < 0.05) and the Caspase-3 activity was enhanced (p < 0.05) in AMI group and Caspase-3-siRNA group. However, the Caspase-3-siRNA group showed lower expression levels of Caspase-3 mRNA/protein and weaker Caspase-3 activity, compared with AMI group (p < 0.05). Furthermore, the apoptosis index and the infarction range of myocardial cells were enhanced in AMI group and Caspase-3-siRNA group (p < 0.05). The apoptosis index and infarction range of myocardial cells in Caspase-3-siRNA group were decreased (p < 0.05). Interestingly, the Left Ventricular End-Diastolic dimension (LVEDd) and the Left Ventricular End-Systolic diameter (LVESd) in AMI group and Caspase-3-siRNA group were improved (p < 0.05), but the Ejection Fraction (EF) and Fractional Shortening (FS) in AMI group and Caspase-3-siRNA group were reduced (p < 0.05). All the LVEDd, LVESd, EF and FS in Caspase-3-siRNA group significantly improved than that of AMI group (p < 0.05).
The downregulation of Caspase-3 mediated by lentivirus interference can decrease the infarct size of myocardial tissue and the apoptosis index of myocardial cells. It also can improve heart function in rats with acute myocardial infarction.
探讨RNA干扰Caspase-3对大鼠急性心肌梗死（AMI）的心脏保护作用。
45只SD大鼠随机分为假手术组、AMI组和Caspase-3-siRNA组。通过结扎前降支（LAD）建立AMI动物模型。假手术组和AMI组大鼠心肌组织注射携带空载体的慢病毒。Caspase-3-siRNA组大鼠心肌组织注射携带Caspase-3 RNA干扰载体的慢病毒。72小时后，通过超声心动图分析评估心脏功能。然后处死大鼠，收集心肌组织。分别采用RT-PCR和Western blot分析每组中Caspase-3 mRNA和蛋白的表达水平。此外，通过氯化三苯基四氮唑（TTC）染色分析梗死面积，通过TUNEL法分析心肌细胞凋亡指数。
与假手术组相比，AMI组和Caspase-3-siRNA组中Caspase-3 mRNA和蛋白的表达水平显著上调（p < 0.05），Caspase-3活性增强（p < 0.05）。然而，与AMI组相比，Caspase-3-siRNA组中Caspase- mRNA/蛋白表达水平较低，Caspase-3活性较弱（p < 0.05）。此外，AMI组和Caspase-3-siRNA组中心肌细胞凋亡指数和梗死范围增加（p < 0.05）。Caspase-3-siRNA组中心肌细胞凋亡指数和梗死范围降低（p < 0.05）。有趣的是，AMI组和Caspase-3-siRNA组中左心室舒张末期内径（LVEDd）和左心室收缩末期直径（LVESd）有所改善（p < 0.05），但AMI组和Caspase-3-siRNA组中射血分数（EF）和缩短分数（FS）降低（p < 0.05）。Caspase-3-siRNA组中所有LVEDd、LVESd、EF和FS均比AMI组显著改善（p < 0.05）。
慢病毒干扰介导的Caspase-3下调可减小心肌组织梗死面积和心肌细胞凋亡指数。它还可改善急性心肌梗死大鼠的心脏功能。
