Electroacupuncture Pretreatment Mitigates Myocardial Ischemia/Reperfusion Injury via XBP1/GRP78/Akt Pathway

Abstract

Myocardial ischemia/reperfusion injury is a common clinical problem and can result in severe cardiac dysfunction. Previous studies have demonstrated the protection of electroacupuncture against myocardial ischemia/reperfusion injury. However, the role of X-box binding protein I (XBP1) signaling pathway in the protection of electroacupuncture was still elusive. Thus, we designed this study and demonstrated that electroacupuncture significantly improved cardiac function during myocardial ischemia/reperfusion injury and reduced cardiac infarct size. Electroacupuncture treatment further inhibited cardiac injury manifested by the decrease of the activities of serum lactate dehydrogenase and creatine kinase-MB. The results also revealed that electroacupuncture elevated the expressions of XBP1, glucose-regulated protein 78 (GRP78), Akt, and Bcl-2 and decreased the Bax and cleaved Caspase 3 expressions. By using the inhibitor of XBP1 in vitro, the results revealed that suppression of XBP1 expression could markedly increase the activities of lactate dehydrogenase and creatine kinase-MB and cell apoptosis, thus exacerbating stimulated ischemia/reperfusion-induced H9c2 cell injury. Compared with stimulated ischemia/reperfusion group, inhibition of XBP1 inhibited the downstream GRP78 and Akt expressions during stimulated ischemia/reperfusion injury. Collectively, our data demonstrated that electroacupuncture treatment activated XBP1/GRP78/Akt signaling to protect hearts from myocardial ischemia/reperfusion injury. These findings revealed the underlying mechanisms of electroacupuncture protection against myocardial ischemia/reperfusion injury and may provide novel therapeutic targets for the clinical treatment of myocardial ischemia/reperfusion injury.

Plasma exosomal miR-142-3p induced by acupuncture protects against heart injury in rat with myocardial infarction by targeting Cofilin-2

“…The acupoint of Neiguan (PC6) is the most advised for the treatment of heart diseases in the theory of Chinese acupuncture. A wealth of evidence showed the bene ts of Neiguan (PC6) acupuncture for attenuating cardiac injury via multi-pathways, such as inhibiting apoptosis, alleviating mitochondrial damage, and decreasing the degree of in ammation [10,22,23]. In the present study, acupuncture at Neiguan (PC6) thickened the left ventricular wall in a rat model of MI and downregulated the expression of CC3.…”

ADSCs‐exo attenuates hepatic ischemia–reperfusion injury after hepatectomy by inhibiting endoplasmic reticulum stress and inflammation

“…ATF-6 transmembrane receptor proteins, which activates the PERK/eIF2α, IRE1α/XBP1, and ATF-6 pathway (Peralta & Brenner, 2011). I/R injury in the heart (N. Wang et al, 2021), brain (Gu et al, 2017), kidney (Y. Zhang et al, 2020), and liver (D. Liu, Jin, et al, 2018) significantly increases GRP78 expression.…”

“…ERS induces GRP78 dissociation from PERK, IRE1α, and ATF‐6 transmembrane receptor proteins, which activates the PERK/eIF2α, IRE1α/XBP1, and ATF‐6 pathway (Peralta & Brenner, 2011). I/R injury in the heart (N. Wang et al, 2021), brain (Gu et al, 2017), kidney (Y. Zhang et al, 2020), and liver (D. Liu, Jin, et al, 2018) significantly increases GRP78 expression. Jiao et al demonstrated that GRP78 expression is elevated in miniature pigs with hepatic I/R and partial resection injury.…”

Repair effect of the poly (D,L-lactic acid) nanoparticle containing tauroursodeoxycholic acid-eluting stents on endothelial injury after stent implantation

“…XBP1 is one of the important proteins that mediate the occurrence of ERS, the effect of XBP1 on cells depends mainly on the strength of the injury and the degree of activation of XBP1. When the mice are pretreatment with small pre-stimulations such as low-frequency electrical stimulation, the low-level expression of XBP1 is induced then the body is provided with adaptive capacity, which is a protective measure, so that the less cell necrosisbody in body during subsequent severe damages such as hypoxia-reperfusion injury ( 61 ). However, if the cells suffer from strong oxidative stress, resulting in high expression of XBP1, it will lead to severe ERS and induce cell necrosis.…”