Y-27632, a Rho-kinase inhibitor, attenuates myocardial ischemia-reperfusion injury in rats

Dong,Li‑Ya; Qiu,Xiao‑Xiao; Zhuang,Yu; Xue,Song

doi:10.3892/ijmm.2019.4097

Y-27632, a Rho-kinase inhibitor, attenuates myocardial ischemia-reperfusion injury in rats

Authors:
- Li‑Ya Dong
- Xiao‑Xiao Qiu
- Yu Zhuang
- Song Xue
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Affiliations: Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China, Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China
Published online on: February 14, 2019 https://doi.org/10.3892/ijmm.2019.4097
Pages: 1911-1919

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Abstract

The present study aimed to evaluate the cardioprotective effects of a Rho‑kinase inhibitor, Y‑27632, and the underlying mechanisms. A rat model of myocardial ischemia‑reperfusion (I/R) injury was generated by ligation of the coronary artery, and global ischemia of isolated rat hearts was conducted using the Langendorff system. Staining with triphenyltetrazolium chloride (TTC) and hematoxylin and eosin was performed to analyze the myocardial infarct size and histopathological alterations of the I/R‑induced rat heart. In addition, coronary flow, myocardial contractility and an electrocardiogram were analyzed. The effects of Y‑27632 on inflammatory cytokines and cardiac enzymes in the serum were assessed by ELISA. The expression of apoptosis‑ and inflammation‑associated proteins was also analyzed via western blotting. Rats in the Y‑27632 group exhibited alleviated myocardial I/R injury according to TTC staining and histopathological diagnosis. Additionally, Y‑27632 restored the ST segment. The data of coronary flow and myocardial contractility in isolated rat hearts indicated that Y‑27632 improved heart function following I/R. The levels of inflammatory cytokines and cardiac enzymes in the serum were downregulated by Y‑27632. The mitogen‑activated protein kinase (MAPK) and nuclear factor (NF)‑κB signaling pathways were inhibited by Y‑27632. Furthermore, apoptosis‑associated protein expression in rats and the isolated hearts was effectively inhibited by Y‑27632. In conclusion, the findings of the present study indicated that Y‑27632 attenuated myocardial injury via inhibiting the activation of the MAPK and NF‑κB signaling pathways; thus, apoptosis and the inflammatory response were suppressed.

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