Acupuncture Attenuated Myocardial Ischemia-Reperfusion Injury by Inhibiting SPHK1/TIMP1 Signaling Pathway

Abstract

Background: Myocardial ischemia-reperfusion (I/R) injury is a difficult clinical presentation in patients with ischemic heart after re-establishing blood flow. It can induce arrhythmia, ventricular systolic dysfunction, and enlarge the infarct size. Acupuncture (Acu), as a part of traditional Chinese medicine (TCM) therapy, has acceptable effectiveness and minimal side effects. This attracted increasing interest in managing myocardial I/R injury. However, its mechanism of action is in not fully understood. This study evaluated acupuncture approach for myocardial I/R injury and explored its mechanism of action in rats, using coronary artery ligation to simulate myocardial I/R injury. Methods: Before modeling, rats were pinpricked at Gongsun (SP 4), Neiguan (PC 4), Guanyuan (CV 4), Juque (CV 14), Tiantu (CV 22), Xinshu (BL 15), Li Dui (ST 45) points. After modeling, rats were immediately injected with recombinant adenovirus of sphingosine kinases type 1 (SPHK1) pDC316 overexpression (pDC-SPHK1). The protective effects of acupuncture on myocardial I/R injury were shown to be mediated through histomorphology, cardiomyocyte apoptosis, myocardial enzymes, and anti-inflammatory response. Results: Multiple-point acupuncture inhibited the activation of SPHK1/tissue inhibitor of metalloproteinase-1 (TIMP1) signaling pathway in myocardial tissue. Acupuncture intervention reduced left ventricular dysfunction, myocardial infarction area, cardiomyocyte apoptosis, and excessive inflammation caused by I/R. SPHK1 overexpression significantly reversed these protective effects of acupuncture intervention on myocardial I/R injury. Conclusions: Taken together, multi-point acupuncture may be an effective alternative therapy to prevent myocardial I/R injury.