Dl-3-n-butylphthalide attenuates myocardial ischemia reperfusion injury by suppressing oxidative stress and regulating cardiac mitophagy via the PINK1/Parkin pathway in rats

Dongqin Zhang; Nan Zheng; Xiaoli Fu; Jian Shi; Jun Zhang

doi:10.21037/jtd-22-585

Dl-3-n-butylphthalide attenuates myocardial ischemia reperfusion injury by suppressing oxidative stress and regulating cardiac mitophagy via the PINK1/Parkin pathway in rats

J Thorac Dis. 2022 May;14(5):1651-1662. doi: 10.21037/jtd-22-585.

Authors

Dongqin Zhang^{1

2}, Nan Zheng³, Xiaoli Fu², Jian Shi⁴, Jun Zhang^{1

3}

Affiliations

¹ Department of Internal Medicine, Hebei Medical University, Shijiazhuang, China.
² Department of Geriatrics, Baoding No. 1 Central Hospital, Baoding, China.
³ Department of Cardiology, Cangzhou Central Hospital, Cangzhou, China.
⁴ Department of Cardiovascular Surgery, Baoding No. 1 Central Hospital, Baoding, China.

Abstract

Background: Acute myocardial infarction (AMI) is one of the leading causes of mortality worldwide. Undesirable myocardial damage may occur during reperfusion of the ischemic myocardium, and this is known as "ischemic reperfusion injury" (IRI). Currently, there are few effective drugs to alleviate IRI. Dl-3-n-butylphthalide (NBP) is recommended for the treatment of acute ischemic stroke in China. This study investigated the effects of NBP on IRI and its underlying mechanisms.

Methods: The left anterior descending (LAD) coronary arteries of rats were occluded for 30 minutes and reperfused for 6 hours to establish the ischemia/reperfusion (I/R) model. NBP was administered intraperitoneally 2 hours before modeling and immediately after reperfusion. At 6 hours after reperfusion, 2,3,5-triphenyltetrazolium chloride (TTC) staining, enzyme-linked immunosorbent assay (ELISA), oxidative stress index, myocardial injury index, hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), real-time polymerase chain reaction (PCR), immunofluorescence staining, and Western blot analyses were performed to investigate the protective effects of NBP against IRI.

Results: In the rat I/R model, NBP remarkably reduced the myocardial infarct size, alleviated myocardial injury and oxidative stress, improved the pathological alteration of cardiomyocytes and mitochondria, and upregulated mitophagy. In addition, the study demonstrated that the protective effects of NBP against IRI involved mitophagy mediated by the PTEN-induced putative kinase protein-1 (PINK1)/Parkin signaling pathway.

Conclusions: NBP was able to protect the myocardium from IRI in rats through inhibiting oxidative stress and activating mitophagy, mediated by the PINK1/Parkin pathway.

Keywords: Dl-3-n-butylphthalide (NBP); ischemic reperfusion injury (IRI); mitophagy; oxidative stress.