ABSTRACT
Salidroside (Sal), a natural extract of Rhodiola rosea, shows a latent effect on protecting cardiovascular system. Our study explored the effect of salidroside on ischemia-reperfusion (I/R) injury in rat heart. I/R was performed on Wistar rat hearts, and Sal pretreatment was performed in I/R rats. Cardiac marker enzyme, myocardial infarct size, malondialdehyde (MDA) and superoxide dismutase (SOD) content were then measured. Compared with the untreated group, Sal pretreatment observably ameliorated the cardiac function, decreased the myocardial infarct size, reduced the levels of cardiac lactate creatine kinase-MB (CK-MB) and dehydrogenase (LDH), and inhibited the anti-oxidative stress. In addition, Sal treatment also significantly inhibited autophagy and apoptosis, which could be partially reversed by Rapamycin (RAPA), an autophagic agonist. Furthermore, Sal treatment attenuated autophagy by up-regulating the expression of hsa_circ_0000064 (circ-0000064) and Rapamycin (RAPA) treatment abolished it. Our study showed that Sal protected the heart from I/R injury, which might berelated to the upregulation of circ-0000064 and the inhibition of autophagy.
Subject(s)
Glucosides/metabolism , Myocytes, Cardiac/metabolism , Phenols/metabolism , RNA, Circular/genetics , Animals , Apoptosis/drug effects , Autophagy/drug effects , Gene Expression Regulation/genetics , Glucosides/pharmacology , Male , Malondialdehyde/metabolism , Myocardial Infarction/metabolism , Myocardial Reperfusion Injury/metabolism , Oxidative Stress/drug effects , Phenols/pharmacology , Plant Extracts , RNA, Circular/metabolism , Rats , Rats, Wistar , Reperfusion Injury/drug therapy , Rhodiola , Superoxide Dismutase/metabolismABSTRACT
Accumulating evidence suggests that circular RNAs have the abilities to regulate gene expression during the progression of sepsis-associated acute kidney injury. Circular RNA VMA21 (circVMA21), a recent identified circular RNA, could reduce apoptosis to alleviate intervertebral disc degeneration in rats and protect WI-38 cells from lipopolysaccharide-induced injury. However, the role of circVMA21 in sepsis-associated acute kidney injury (sepsis-associated AKI) is unknown. In this study, we first demonstrated that circVMA21 alleviated sepsis-associated AKI by reducing apoptosis and inflammation in rats and HK-2 cells. Additionally, to explore the molecule mechanism underlying the amelioration, after the bioinformatics analysis, we confirmed that miR-9-3p directly bound to circVMA21 by luciferase and RNA immunoprecipitation assay, and the effector protein of miR-9-3p was SMG1. Furthermore, the oxidative stress caused by sepsis-associated AKI was down-regulated by circVMA21. In conclusion, circVMA21 plays an important role in the regulating sepsis-associated AKI via adjusting miR-9-39/SMG1/inflammation axis and oxidative stress.