Dexmedetomidine postconditioning suppresses myocardial ischemia/reperfusion injury by activating the SIRT1/mTOR axis

Abstract

Myocardial ischemia/reperfusion (MI/R) triggers a complicated chain of inflammatory reactions. Dexmedetomidine (Dex) has been reported to be important in myocardial disorders. We evaluated the role of Dex in MI/R injury via the silent information regulator factor 2-related enzyme 1 (SIRT1)/mammalian target of rapamycin (mTOR) signaling pathway. First, Dex was immediately injected into rat models of MI/R injury during reperfusion. After Evans Blue-triphenyl tetrazolium chloride (TTC) and Hematoxylin–Eosin (H-E) staining, MI/R injury was observed. The extracted serum and myocardial tissues were used to detect oxidative stress and the inflammatory response. Western blot analysis was performed to evaluate MI/R autophagy and the levels of proteins associated with the SIRT1/mTOR axis. The effects of the combination of Dex and SIRT1 inhibitor EX527 on MI/R injury and autophagy were evaluated. Finally, the mechanism of Dex was tested, and autophagy levels and the levels of proteins associated with the SIRT1/mTOR signaling pathway were assessed in MI/R rats. The results of the present study suggested that Dex relieved MI/R injury, reduced cardiomyocyte apoptosis, oxidative stress and inflammatory reactions, up-regulated the SIRT1/mTOR axis and decreased overautophagy in MI/R rats. SIRT1 inhibitor EX527 attenuated the protective effects of Dex. Our study demonstrated that Dex alleviated MI/R injury by activating the SIRT1/mTOR axis. This investigation may offer new insight into the treatment of MI/R injury.

Dexmedetomidine Ameliorates Hippocampus Injury and Cognitive Dysfunction Induced by Hepatic Ischemia/Reperfusion by Activating SIRT3-Mediated Mitophagy and Inhibiting Activation of the NLRP3 Inflammasome in Young Rats

“…Moreover, treatment with the selective SIRT3 inhibitor, 3-TYP, reversed the positive effects of Dex. Intriguingly, Dex treatment had no such effects on the SIRT1 expression and activity, unlike previous studies in which Dex treatment played a protective role by activating SIRT1 pathway [ 56 , 57 ]. Hence, we speculated that due to the limited ability of Dex treatment to increase the expression of SIRT1, its activation effect cannot be shown obviously when SIRT1 is already activated.…”

AMPK/SIRT1 Pathway is Involved in Arctigenin-Mediated Protective Effects Against Myocardial Ischemia-Reperfusion Injury

“…Several studies have shown that SIRT1 is also of outstanding value in myocardial ischemic disease. For example, Zhang X et al reported that Dex inhibits myocardial ischemia/reperfusion injury by activating the SIRT1/mTOR axis ( Zhang et al, 2020 ). Meanwhile, Shu L et al illustrated that lncRNA ANRIL promoted the up-regulation of SIRT1 expression by down-regulating miR-7-5p, thus playing a protective role in H9C2 myocardial cell injury induced by hypoxia ( Shu et al, 2020 ).…”

NAD+ improved experimental autoimmune encephalomyelitis by regulating SIRT1 to inhibit PI3K/Akt/mTOR signaling pathway

“…Deacetylation of Beclin-1 lysine residue by SIRT1 affects the formation of autophagosomes and subsequent biological effects, suggesting that Beclin-1 is a deacetylation target of SIRT1. SIRT1-mediated autophagy plays an important role in nerve cell injury, myocardial cell remodeling and other diseases [ 25 , 26 ]. However, there are few studies on whether it also plays such a regulatory role in thymus autophagy.…”