scholarly journals The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats

Open Medicine ◽  
2020 ◽  
Vol 16 (1) ◽  
pp. 047-057
Author(s):  
Lei Gong ◽  
Xuyang Wang ◽  
Jinyu Pan ◽  
Mingjun Zhang ◽  
Dian Liu ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Mtor Signaling ◽  
Maximal Rate ◽  
H9c2 Cells ◽  
Mtor Signaling Pathway ◽  
Cardioprotective Effects

AbstractObjectiveThe 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.MethodsSprague-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) + DGZ (1 mg/kg). The I/R model was induced with 30 min of left anterior descending occlusion followed by 120 min of reperfusion.ResultsIn vivo pretreatment with RSV and DGZ, respectively, showed a significant reduction of infarction size, a significant increase in the levels of left ventricular systolic pressure, and maximal rate increase in left ventricular pressure (+dp/dtmax), decrease in the levels of left ventricular end-diastolic pressure (LVEDP), maximal rate of decrease of left ventricular pressure (−dp/dtmax) and activity of cardiac enzymes of creatine kinase (CK), creatine kinase MB isoenzymes (CK-MB), and hyper-tensive cardiac troponin I compared with the I/R group. H9C2 cells were exposed to hypoxia/reoxygenation to simulate an I/R model. In vitro administration of 25 µM RSV and 50 µM DGZ significantly enhanced cell viability, upregulated the expression levels of p-PI3K, p-Akt, p-mTOR, and Bcl-2, whereas it downregulated cleaved-caspase3, Bax. TUNEL assay indicated that pretreatment with RSV and DGZ decreased the apoptosis of H9C2 cells.ConclusionThe combination of RSV and DGZ significantly enhances the cardioprotective effects compared with RSV or DGZ alone. RSV and DGZ have the potential cardioprotective effects against I/R injury by activating the PI3K/AKt/mTOR signaling pathway.

Possible involvement of PI3K/AKT/mTOR signaling pathway in the protective effect of selegiline (deprenyl) against memory impairment following ischemia reperfusion in rat

Neuropeptides ◽  
2019 ◽  
Vol 77 ◽  
pp. 101942 ◽  
Author(s):  
Hossein Amini-Khoei ◽  
Elham Saghaei ◽  
Gholam-Reza Mobini ◽  
Milad Sabzevary-Ghahfarokhi ◽  
Reza Ahmadi ◽  
...  
Keyword(s):  
Protective Effect ◽  
Signaling Pathway ◽  
Memory Impairment ◽  
Ischemia Reperfusion ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway

Kaempferol reversals retinal ischemia/reperfusion (IR) injury through activating of PI3K/Akt/mTOR signaling pathway

2021 ◽  
Author(s):  
Da Sun ◽  
Fusheng Shang ◽  
Dagui Chen ◽  
Wenwen Wang ◽  
lili lin
Keyword(s):  
Oxidative Damage ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion ◽  
Retinal Ischemia ◽  
Mtor Signaling ◽  
Cell Counting ◽  
Mtor Signaling Pathway ◽  
Autophagy Gene ◽  
Retinal Vascular Occlusion

Abstract Purpose Retinal ischemia/reperfusion (IR) injury is associated with many ocular diseases, including acute glaucoma, diabetic retinopathy, and retinal vascular occlusion. However, currently there are no effective medications to prevent the development ofretinal IR injury.Kaempferol is a kind of plant extract which has showed an excellent ability to inhibit the inflammation.. Materials and Methods In this study, both in vitro and in vivo retinaloxidative damage models were established.Cell viability was assessed by Cell Counting Kit-8 assay. Apoptosis was examined using flow cytometry analysis.Atherosclerotic lesion analysis was performed using hematoxylin-eosin staining,The expressions of Inflammatory cytokines were detected by quantitative real-time PCR and ELISA respectively.The effect of expression of apoptosis、utophagy and the PI3K/Akt/mTOR signaling pathway related pathway was evaluated by Western blot. Results We found kaempferol was able to protect the viability of ARPE-19 cells against oxidative damage by reducing its apoptosis. In addition, it also kept structurally complete epithelium, stroma and endothelium of cornea after oxidative damage. Moreover, it also able to reduce the expression of inflammatory cytokines and increased the expression of anti-inflammatory cytokines.Kaempferol was able to enhanced the expression of anti-apoptotic genes BCL-2, and reduced the expression of autophagy gene Beclin 1 and increased the expression of anti-autophagy gene LC-3,was also able to enhance the expression PI3K and the phosphorylation ofAkt andmTOR. Conclusion Kaempferolreversals retinal ischemia/reperfusion (IR) injury through activating of PI3K/Akt/mTOR signaling pathway.

scholarly journals Aescin Protects Neuron from Ischemia-Reperfusion Injury via Regulating the PRAS40/mTOR Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xinjie Gao ◽  
Heng Yang ◽  
Jiabin Su ◽  
Weiping Xiao ◽  
Wei Ni ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Intravenous Thrombolysis ◽  
Mtor Signaling ◽  
Dependent Manner ◽  
Protective Effects ◽  
Mtor Signaling Pathway

Ischemic stroke is one of the major causes of disability; widely use of endovascular thrombectomy or intravenous thrombolysis leads to more attention on ischemia-reperfusion injury (I/R injury). Aescin, a natural compound isolated from the seed of the horse chestnut, has been demonstrated anti-inflammatory and antiedematous effects previously. This study was aimed at determining whether aescin could induce protective effects against ischemia-reperfusion injury and exploring the underlying mechanisms in vitro. Primary cultured neurons were subjected to 2 hours of oxygen-glucose deprivation (OGD) followed by 24 hours of simulated reperfusion. Aescin, which worked in a dose-dependent manner, could significantly attenuate neuronal death and reduce lactate dehydrogenase (LDH) release after OGD and simulated reperfusion. Aescin treatment at a concentration of 50 μg/ml provided protection with fewer side effects. Results showed that aescin upregulated the phosphorylation level of PRAS40 and proteins in the mTOR signaling pathway, including S6K and 4E-BP1. However, PRAS40 knockdown or rapamycin treatment was able to undermine and even abolish the protective effects of aescin; meanwhile, the levels of phosphorylation PRAS40 and proteins in the mTOR signaling pathway were obviously decreased. Hence, our study demonstrated that aescin provided neuronal protective effects against I/R injury through the PRAS40/mTOR signaling pathway in vitro. These results might contribute to the potential clinical application of aescin and provide a therapeutic target on subsequent cerebral I/R injury.

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