2020
DOI: 10.1515/med-2021-0005
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The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats

Abstract: Objective The purpose of the present study was to evaluate the role of co-treatment of rosuvastatin (RSV) and dapagliflozin (DGZ) preconditioning in myocardium ischemia/reperfusion (I/R) injury and to further investigate the underlying mechanism. Methods Sprague-Dawley (SD) rats (n = 25) were divided into five groups randomly: (1) Sham, (2) I/R, (3) I/R + RSV (10 mg/kg), (4) IR + DGZ (1 mg/kg), and (5) I/R + RSV (10 mg/kg) + … Show more

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Cited by 19 publications
(17 citation statements)
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“…In our study, DAPA inhibited the ratio of p-AKT/AKT and p-mTOR/mTOR, indicating that effects of DAPA on cardiac function, remodeling, inflammatory cytokines, and cell apoptosis might be associated with the inhibition of the PI3K/AKT/mTOR pathway. Nevertheless, a recent study showed that DAPA reduced myocardial apoptosis by activating the PI3K/AKT/mTOR signaling pathway in a myocardial ischemia/reperfusion injury model [39]; this conflicted our findings; i.e., H9C2 cells exposed to hypoxia/resoxygenation were used to simulate a myocardial ischemia/reperfusion injury (I/R) model. Besides, an in vitro model was used, whereas our study used an in vivo model.…”
Section: Discussioncontrasting
confidence: 99%
“…In our study, DAPA inhibited the ratio of p-AKT/AKT and p-mTOR/mTOR, indicating that effects of DAPA on cardiac function, remodeling, inflammatory cytokines, and cell apoptosis might be associated with the inhibition of the PI3K/AKT/mTOR pathway. Nevertheless, a recent study showed that DAPA reduced myocardial apoptosis by activating the PI3K/AKT/mTOR signaling pathway in a myocardial ischemia/reperfusion injury model [39]; this conflicted our findings; i.e., H9C2 cells exposed to hypoxia/resoxygenation were used to simulate a myocardial ischemia/reperfusion injury (I/R) model. Besides, an in vitro model was used, whereas our study used an in vivo model.…”
Section: Discussioncontrasting
confidence: 99%
“…Study evidence has demonstrated that apoptosis is one of the main pathogenic mechanisms of MIRI. For example, Gong et al reported that I/R resulted in myocardial cell apoptosis through detection of cleaved-caspase 3, Bax, and TUNEL and that cotreatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis in H/R-induced H9c2 cells [ 47 ]. Similarly, treatment with LBAG significantly inhibited apoptosis, by reducing Bax and cleaved-caspase 3 expressions and alleviating the Bcl-2 levels in heart tissues of MIRI rats.…”
Section: Discussionmentioning
confidence: 99%
“…Rats in the two treatment groups were orally administrated with Dap dissolved in pure water (average 1 mg/ kg/ day) for 8 weeks. Dap dosage was selected on the basis of previous studies, and 1 mg/ kg Dap has the sufficient in vivo cardioprotective effects ( Tanajak, 2018 ; Gong et al, 2021 ). Body weight was recorded every week.…”
Section: Methodsmentioning
confidence: 99%