Abstract
Our previous studies have reported that agonist of α7 nicotinic acetylcholine receptors prevented electrophysiological dysfunction of rats with ischaemic cardiomyopathy (ICM) by eliciting the cholinergic anti-inflammatory pathway (CAP). Adenosine monophosphate-activated protein kinase (AMPK) signalling is widely recognized exerting cardioprotective effect in various cardiomyopathy. Here, we aimed to investigate whether the protective effects of the CAP are associated with AMPK signalling in ICM. In vivo, coronary artery of rats was ligated for 4 weeks to induce the ICM and then treated with PNU-282987 (CAP agonist) and BML-275 dihydrochloride (AMPK antagonist) for 4 weeks. In vitro, primary macrophages harvested from rats were induced inflammation by Lipopolysaccharide (LPS) treatment and then treated with PNU-282987 and BML-275 dihydrochloride. In vivo, exciting CAP by PUN-282987 elicited an activation of AMPK signalling, alleviated ventricular remodeling, modified the cardiac electrophysiological function, reduced the cardiac expression of collagens and inflammatory cytokines and maintained the integrity of ultrastructure in the ischemic heart. However, the benefits of CAP excitation were blunted by AMPK signaling antagonization. In vitro, excitation of the CAP was observed inhibiting the nuclear transfer of NF-κB p65 of macrophages and promoting the transformation of Ly-6Chigh macrophages into Ly-6Clow macrophages. However, inhibiting AMPK signalling by BML-275 dihydrochloride reversed the CAP effect on LPS-treated macrophages. Finally, our findings suggest that eliciting the CAP modulates the inflammatory response in ICM through regulating AMPK signalling.