Drug Design, Development and Therapy (Oct 2020)
Alprostadil Injection Attenuates Coronary Microembolization-Induced Myocardial Injury Through GSK-3β/Nrf2/HO-1 Signaling-Mediated Apoptosis Inhibition
Abstract
Zhenbai Qin, Binghui Kong, Jing Zheng, Xiantao Wang, Lang Li Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, ChinaCorrespondence: Lang LiDepartment of Cardiology, The First Affiliated Hospital of Guangxi Medical University, No. 21 Shuangyong Road, Qingxiu District, Nanning, Guangxi 530021, ChinaTel +86 0771-5331171Email [email protected]: Coronary microembolization (CME) results in progressive contractile dysfunction associated with cardiomyocyte apoptosis. Alprostadil injection improves microcirculation, which is effective in treating various cardiovascular disorders. However, the therapeutic effects of alprostadil in CME-induced myocardia injury remain unknown. Therefore, we evaluated the effects of alprostadil injection on cardiac protection in a rat model of CME and explored the underlying mechanisms.Methods: A rat model of CME was established by injecting polyethylene microspheres into the left ventricle. After injection of microspheres, rats in the alprostadil group received alprostadil via tail vein within 2 minutes. Cardiac function, histological alterations in myocardium, serum c-troponin I (cTnI) levels, myocardium adenosine triphosphate (ATP) concentrations, the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) content in myocardium, and myocardial apoptosis-related proteins were detected 12 hours after CME modeling.Results: Compared with the Sham group, ATP concentrations, SOD activity in the myocardium, and cardiac function were significantly decreased in a rat model of CME. In addition, serum cTnI levels, MDA content, expression levels of pro-apoptotic proteins, and the number of TUNEL-positive nuclei were remarkably higher in CME group than those in the Sham group. However, alprostadil treatment notably reduced serum cTnI levels and expression levels of pro-apoptotic proteins, while noticeably improved cardiac function, and accelerated SOD activity in the myocardium following CME. Additionally, it was unveiled that the protective effects of alprostadil injection inhibit CME-induced myocardial apoptosis in the myocardium potentially through regulation of the GSK-3β/Nrf2/HO-1 signaling pathway.Conclusion: Alprostadil injection seems to significantly suppress oxidative stress, alleviate myocardial apoptosis in the myocardium, and improve cardiac systolic and diastolic functions following CME by regulating the GSK-3β/Nrf2/HO-1 signaling pathway.Keywords: coronary microembolization, alprostadil injection, apoptosis, GSK-3β/Nrf2/HO-1 signaling pathway
