Objectives Electroacupuncture (EA) therapy has been widely accepted as a useful therapeutic technique with low or no risk in the clinical prevention from cardiac disease. However, the physiological mechanism underlying this protective effect remains unclear. The current study investigates the effects of EA pretreatment on myocardial ischaemia/reperfusion (MI/R) injury in mice and its possible signalling pathway.

Methods Up to 100 C57BL/6 mice were randomly divided into Sham, MI/R, EA + MI/R, EA (-) + MI/R, and AM630 + EA + MI/R groups (n = 20, each group). The mice in EA + MI/R and AM630 + EA + MI/R groups received EA pretreatment for 30 min before MI/R. Five minutes before EA pretreatment, mice received intraperitoneal injection of the cannabinoid receptor type 2 (CB2) selective inhibitor AM630 (20 mg/kg) or vehicle. Left anterior descending coronary artery ligature in mice was performed for 30 min, and the myocardium was reperfused for 3 h after knot release (for apoptosis, oxidative stress, and CB2 expression) or 24 h (for cardiac function and infarct size determination).

Results EA pretreatment significantly ameliorated MI/R-induced myocardial injury, evidenced by increased cardiac function, reduced infarct size, and decreased apoptosis in mice. This was associated with a reduction of oxidative stress in the infarcted myocardium, which was through CB2. Administration of AM630 before EA pretreatment didn’t improve cardiac function and inhibit oxidative stress. The expression of CB2 was up-regulated in hearts after EA pretreatment, as well as content of N-arach-idonoylethanolamine-anandamide (AEA) and 2-arachidonylglycerol (2-AG) in heart tissue. Furthermore, the expression of AMPK and PGC-1α in the left ventricular myocardial tissue was decreased in MI/R group, while increased in EA pretreatment group. Preinjection of CB2 inhibitor AM630 could partially decreased the EA pretreatment-mediated AMPK or PGC-1α expression.

Conclusions Pretreatment with EA increases the production of endocannabinoid, which elicits protective effects against MI/R injury through CB2 activation. The mechanism of this effect is related to the activation of AMPK/PGC-1α pathways, followed by an inhibition of oxidative stress. These results suggest a novel mechanism of EA pretreatment-induced protective effects on MI/R.