Lentivirus Mediated Interference of Caspase-3 Expression Ameliorates the Heart Function on Rats with Acute Myocardial Infarction

Aim: To explore the heart protection effects by RNA interference of Caspase-3 on rat acute myocardial infarction (AMI).

Materials And Methods: 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.

Results: 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).

Conclusions: 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.