Captopril inhibits calpain‑mediated apoptosis of myocardial cells in diabetic rats and improves cardiac function

Dong,Li‑Ya; Yao,Li‑Ping; Zhao,Jing; Jin,Ke‑Ke; Qiu,Xiao‑Xiao

doi:10.3892/mmr.2018.9192

Captopril inhibits calpain‑mediated apoptosis of myocardial cells in diabetic rats and improves cardiac function

Authors:
- Li‑Ya Dong
- Li‑Ping Yao
- Jing Zhao
- Ke‑Ke Jin
- Xiao‑Xiao Qiu
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Affiliations: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, P.R. China, Department of Pathophysiology, Anqing Medical College, Anqing, Anhui 246052, P.R. China, Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: June 19, 2018 https://doi.org/10.3892/mmr.2018.9192
Pages: 2300-2306

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Abstract

To explore the effects of captopril on calpain‑mediated apoptosis of myocardial cells and cardiac function in diabetic rats, 30 adult male Sprague‑Dawley rats were randomly divided into three groups: Negative control (NC group), untreated diabetic rats (DM group) and diabetic rats treated with captopril (Cap group). Diabetes was induced by streptozotocin injection. Captopril was intragastrically administered at a daily dose of 50 mg/kg for 12 weeks; the NC and DM groups received an equivalent volume of saline. After 12 weeks of treatment, left ventricular systolic pressure (LVSP), left ventricular end‑diastolic pressure (LVDEP), maximal rate of left ventricular pressure increase (+dp/dtmax), maximal rate of left ventricular pressure decrease (‑dp/dtmax) and left ventricular mass index (LVMI) were measured. The levels of calpain‑1, calpain‑2, B‑cell lymphoma (Bcl)‑2, Bcl‑2 associated protein X (Bax) and total caspase‑3 were detected in cardiac tissue by western blot analysis. The apoptotic index (AI) was assessed with a terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling assay. The ultrastructure of cardiac tissue was determined by transmission electron microscopy. Compared with the NC group, LVDEP and LVMI were increased, whereas LVSP, +dp/dtmax and ‑dp/dtmax were decreased in the DM group. In the Cap group, LVDEP and LVMI were decreased, whereas LVSP, +dp/dtmax and ‑dp/dtmax were increased compared with the DM group. Bcl‑2 protein expression was decreased, whereas the levels of calpain‑1, calpain‑2, Bax and total caspase‑3 protein were increased in the DM group, compared with the NC group. Cap treatment increased Bcl‑2 protein expression and decreased calpain‑1, calpain‑2, Bax and total caspase‑3 protein expression compared with the DM group. Additionally, the AI was increased in the DM group compared with the NC group, and decreased in the Cap group compared with the DM group. Furthermore, ultrastructural examination demonstrated that myocardial cell injury was reduced in the Cap group compared with the DM group. Therefore, captopril improved myocardial structure and ventricular function, by inhibiting calpain‑1 and calpain‑2 activation, increasing Bcl‑2 expression, reducing Bax expression and subsequently inhibiting caspase‑3‑dependent apoptosis.

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