scholarly journals Remifentanil preconditioning alleviates myocardial ischemia/reperfusion injury in rats via activating Jagged-1/Notch signaling pathway

2021 ◽  
Author(s):  
Dejun Cao ◽  
Shaoxing Liu ◽  
Mengchang Yang ◽  
Keyu Xie ◽  
Zhuo Zheng ◽  
...  

Ischemic heart diseases have emerged as great threats to human health. Nowadays, restoration of cardiac blood flow supply is widely regarded as a feasible treatment choice for ischemic heart diseases; however, this intervention would contradictorily elicit reperfusion injury. Recently, myocardial ischemia/reperfusion injury (MI/RI) has aroused widespread public concerns. Remifentanil, an ultra-short acting opioid analgesic, is frequently used for surgical anesthesia. Previous studies have demonstrated the cardioprotective effects of remifentanil preconditioning in clinical practice and in vitro experimental models; however, its exact mechanisms remain largely unclear. This study aimed to further evaluate the protective effects of remifentanil preconditioning against MI/RI and elucidate the potential molecular mechanisms. Rat models of MI/RI were successfully established via ligation of left anterior descending coronary artery for 30 minutes and restoration of blood flow for 2 hours. Herein, animal experiments displayed that remifentanil preconditioning could alleviate myocardial damage in rat models of MI/RI. Consistently, cell model experiments implied that remifentanil preconditioning attenuated hypoxia/reoxygenation exposure-induced injury in rat cardiomyocytes. Moreover, our findings verified the involvement of Notch signaling pathway in the protective effects of remifentanil preconditioning. In addition, mechanistic studies revealed that remifentanil preconditioning could up-regulate Jagged-1 expression and that Jagged-1 mediated the cardioprotective effects of remifentanil preconditioning through activating Notch signaling pathway. Taken together, our data indicate that remifentanil preconditioning ameliorates myocardial damage in rat MI/RI models via Jagged-1-mediated Notch signaling pathway activation. Thus, this study may offer some novel clues for understanding the cardioprotective mechanisms of remifentanil preconditioning against MI/RI.

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Xilan Tang ◽  
Jianxun Liu ◽  
Wei Dong ◽  
Peng Li ◽  
Lei Li ◽  
...  

Organic acids in Chinese herbs, the long-neglected components, have been reported to possess antioxidant, anti-inflammatory, and antiplatelet aggregation activities; thus they may have potentially protective effect on ischemic heart disease. Therefore, this study aims to investigate the protective effects of two organic acids, that is, citric acid and L-malic acid, which are the main components ofFructus Choerospondiatis, on myocardial ischemia/reperfusion injury and the underlying mechanisms. Inin vivorat model of myocardial ischemia/reperfusion injury, we found that treatments with citric acid and L-malic acid significantly reduced myocardial infarct size, serum levels of TNF-α, and platelet aggregation.In vitroexperiments revealed that both citric acid and L-malic acid significantly reduced LDH release, decreased apoptotic rate, downregulated the expression of cleaved caspase-3, and upregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation injury. These results suggest that both citric acid and L-malic acid have protective effects on myocardial ischemia/reperfusion injury; the underlying mechanism may be related to their anti-inflammatory, antiplatelet aggregation and direct cardiomyocyte protective effects. These results also demonstrate that organic acids, besides flavonoids, may also be the major active ingredient ofFructus Choerospondiatisresponsible for its cardioprotective effects and should be attached great importance in the therapy of ischemic heart disease.


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