Penehyclidine hydrochloride post‑conditioning reduces ischemia/reperfusion‑induced cardiomyocyte apoptosis in rats

Tan,Hongbao; Chen,Li; Ma,Jun

doi:10.3892/etm.2017.5089

Penehyclidine hydrochloride post‑conditioning reduces ischemia/reperfusion‑induced cardiomyocyte apoptosis in rats

Authors:
- Hongbao Tan
- Li Chen
- Jun Ma
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Affiliations: Department of Anesthesiology, Beijing Anzhen Hospital of Capital Medical University, Beijing 100029, P.R. China, Department of Nephrology, The Second People's Hospital of Hunan, Changsha, Hunan 410007, P.R. China
Published online on: September 1, 2017 https://doi.org/10.3892/etm.2017.5089
Pages: 4272-4278
Copyright: © Tan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ischemic heart disease is a major cause of mortality and disability worldwide. Timely reperfusion is currently the most effective method of treating ischemic heart disease; however, abrupt reperfusion may cause ischemia/reperfusion (I/R) injury. Apoptosis serves an important role in the progression of myocardial I/R injury and it has been demonstrated that the mitochondria are the center of regulation for apoptosis. Penehyclidine hydrochloride (PHC) is used during surgery and has recently been identified as a new type of anticholinergic drug. It has been demonstrated in vivo that pretreatment with PHC reduces myocardial apoptosis in rat hearts. The present study aimed to investigate the effects of PHC post‑conditioning on myocardial cell apoptosis in a rat model of myocardial I/R and to determine whether the mitochondria‑induced pathway was activated. Male Wistar rats were evenly and randomly categorized into 4 experimental groups as follows: i) Sham group; ii) I/R group; iii) PHC+sham group; and iv) PHC+I/R group. A PHC (1 mg/kg) post‑conditioning approach (5 min before reperfusion) was used in addition to I/R in the PHC‑treated groups. Following 3 h reperfusion, flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling staining were performed to measure myocardial cell apoptosis. A JC‑1 staining method was performed to measure the mitochondrial membrane potential of myocardial cells. The expression of Bax, Bcl‑2, voltage dependent anion‑selective channel protein 1 (VDAC1), cytosol cytochrome c (cyt-c) and cleaved caspase‑3 was analyzed using western blotting. PHC post‑conditioning significantly reduced apoptosis in cardiomyocytes, significantly downregulated the expression of Bax, VDAC1, cytosol cytochrome c and cleaved caspase‑3 but significantly upregulated the expression of Bcl‑2. PHC post‑conditioning also restored the mitochondrial membrane potential. Thus, the present study demonstrated that PHC post‑conditioning protects cardiomyocytes against apoptosis in the rat model of myocardial I/R by inhibiting the mitochondria‑induced intrinsic pathway.

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