Quercetin has a protective effect on atherosclerosis via enhancement of autophagy in ApoE−/− mice

摘要

The present study examined the involvement of autophagy as a mechanism in the protective effect of quercetin (QUE) on atherosclerosis (AS) in ApoE^−/− mice. An AS model was established by feeding ApoE^−/− mice a high-fat diet (HFD). Mice were divided into four experimental groups: The model, QUE, 3-methyladenine (3-MA) and QUE + 3-MA groups. Additionally, age-matched wild-type C57BL/6 mice were used as a Control group. Autophagosomes in the aorta were examined using a transmission electron microscope. Aorta pathology, serum lipid accumulation and collagen deposition were determined by hematoxylin and eosin, Oil Red O and Masson staining, respectively. The levels of cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured using ELISA assays. Protein levels of mTOR, microtubule associated protein 1 light chain 3a (LC3), P53 and cyclin dependent kinase inhibitor 1A (P21) in the aorta were analyzed using western blotting. ApoE^−/− mice which were fed HFD exhibited substantial AS pathology, no autophagosomes, higher levels of TNF-α, IL-1β, IL-18 and mTOR and lower ratios of LC3 II/I. All these alterations were ameliorated and aggravated by QUE and 3-MA treatment, respectively. The inhibition of AS by QUE may be associated with the enhancement of autophagy and upregulation of P21 and P53 expression.