Liraglutide attenuates myocardial inflammation and oxidative stress injury in diabetes rats via modulating AMPK/mTOR autophagy signalling / 中国药理学通报

ABSTRACT

Aim To investigate the effeets of liraglutide ( LRG) on myocardial injury in type 2 diabetes melli- tus (T2DM) rats and its mechanisms.Methods For¬ty male SD rats were alloeated into eontrol group, T2DM group, LRG group, and LRG + AMPK inhibitor Compound C group (LRG + CC ).Four weeks later blood glucose and blood lipids of T2DM rats were measured.The eardiae function was measured by echo¬cardiography.The activities of superoxide dismutase (SOD ) , glutathione ( GSH ) and the malondialdehyde (MDA) eontent were assessed with corresponding rea¬gent kits.Cardiomyoeyte apoptosis was analyzed by TXJNEL staining.The expressions of inflammation, oxi-dative stress, apoptosis, autophagy, and AMPK/ mTOR signaling related proteins were deteeted by Western blot.Results Treatment with LRG alleviated hyperglycemia and hyperlipidemia, and improved heart function markers in T2DM rats.LRG inhibited inflam¬mation, oxidative stress and apoptosis and restored au- tophagy in T2DM rats by decreasing the expression of IL-6, TNF-a, IL-lp, N0X2, N0X4, cleaved caspase-3, Bax, p-mTOR/mTOR and the MDA con¬tent , and increasing the expression of Bcl-2, Atg5, Beclin-1 , LC3-II/LC3-I, p-AMPK/AMPK and the ac¬tivities of SOD and GSH.However, these effects were largely abolished by the AMPK inhibitor Compound C.Conclusions LRG exerts a protective role against dia¬betes-induced myocardial injury by ameliorating in-flammation, oxidative stress and apoptosis via the AMPK/mTOR autophagy signaling.