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  1. Houxiang Hu,
  2. Tao Luo,
  3. Rongchuan Yue,
  4. Shuang Zhang,
  5. Ke Li,
  6. Lei Xu,
  7. Houxiang Hu
  1. Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, China


    Objectives Calpains belong to a family of calcium-dependent intracellular cysteine proteases. Previous studies demonstrated that calpain activation contributes substantially to ischaemia/reperfusion (I/R) injury. However, it remains unclear whether administration of calpain inhibitor ameliorates I/R-caused heart injury in vivo.

    AIM The objective of this study was to investigate the role of calpain inhibitor PD150606 (PD) in I/R-induced cardiomyocyte apoptosis.

    Methods Male C57BL/6 mice, 2–4 months of age, were randomly divided into sham, I/R, and PD+I/R group (1 mg/kg by IV injection 30 min before ischaemia). Mice were subjected to ischaemia by ligation of the left anterior descending coronary artery for 45 min, then reperfusion for 3 h. The risk and necrotic areas were assessed by Evans blue dye and triphyenyltertrazolium chloride (TTC) staining, respectively. Myocardial apoptosis was assessed by using TUNEL staining, ELISAs for cytochrome c level, and fluorescence assays for the activity of calpain and caspase-3 activities.

    Results Compared to I/R group, the ratio of infarct to risk size was significantly decreased in PD+I/R group (38.26±1.91% vs 29.53±1.64%). Compared to control, myocardial caspase-3 activity was significantly increased in I/R group, however, it was significantly decreased in PD+I/R group (2.47±0.37, 5.13±0.50 and 3.40±0.39 AMC cleaved pmol/mg protein, respectively). Calpain activity (1.15±0.16, 2.07±0.15 and 1.55±0.10 arbitrary units/mg protein, respectively), cytochrome c concentration (5.66±0.54, 8.38±0.64 and 7.57±0.56 ng/mg protein, respectively), and TUNEL-positive nuclei (0.56±0.05%, 10.16±1.20% and 4.60±0.50%, respectively) were significantly increased in I/R mouse compared with control, but were decreased by PD treatment.

    Conclusions Calpain inhibitor PD treatment is an effective strategy to prevent I/R induced myocardial apoptosis in vivo.

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