Sufentanil protects the rat myocardium against ischemia–reperfusion injury via activation of the ERK1/2 pathway

Abstract

Sufentanil, a lipophilic opioid, is the most frequently used clinical drug for ischemic heart disease. The effects of sufentanil on MAPK signaling in ischemic heart disease were explored. The effects of sufentanil on ischemia-reperfusion (IR)-induced myocardial injury in a rat model were examined. The serum levels of CK, LDH, MDA and SOD, and the activities of Na-K-ATPase and Ca-Mg-ATPase were measured. The levels of total and phosphorylated ERK1/2, JNK, and p38 were measured by western blotting in the heart, and the myocardial H9C2 cell line was studied. Using the Cell Counting Kit-8, the growth rate of H9C2 cells affected by sufentanil was studied. The serum levels of CK, LDH and MDA were higher in the IR group than in the SO and SUF groups. The SOD level, as well as the activities of Na-K-ATPase and Ca-Mg-ATPase, were lower in the SO and SUF groups than in the IR group. The phosphorylated ERK1/2 level was lower in the IR group than in the SO and SUF groups. The growth rate of H9C2 cells increased with the concentration of sufentanil and the exposure time. The phosphorylated ERK level was upregulated by 4-12 h of sufentanil exposure, indicating that the effects were time-dependent. Furthermore, an inhibition of ERK signaling by chemical inhibition suppressed the sufentanil-mediated increase in the growth rate of H9C2 cells. Sufentanil appears to be beneficial for cases of worsening ischemic heart disease. Further studies are necessary before a clinical application is considered.

Protective Effect of Sufentanil on Myocardial Ischemia-Reperfusion Injury in Rats by Inhibiting Endoplasmic Reticulum Stress

“…Wu et al [ 15 ] demonstrated that sufentanil postconditioning could protect the myocardium from I/R by activating PI3K/Akt-GSK-3 β pathway and regulating BCL2-Associated X (Bax) and Bcl-2 expression. Tao and Nuo [ 16 ] found that sufentanil could protect the rat myocardium from I/R injury by activating the ERK1/2 pathway. However, there are not many reports on the involvement of ER stress in the process that sufentanil protects the rat myocardium from IR injury.…”

Sufentanil attenuates inflammation and oxidative stress in myocardial ischemia reperfusion injury via upregulating Sestrin 2 expression and activating AMPK signalling pathway

“…During the reperfusion period, the generation of ROS leads to multiple cellular damage, which is an important risk factor in the occurrence and development of cardiovascular ischemic diseases [19,20]. It has been well reported that sufentanil can decrease the content of MDA, which is the end product of lipid peroxidation and a biomarker for oxidative stress [7,21]. SOD serves as an important anti-oxidase, which participates in protecting against oxidative stress during myocardial I/R injury [22,23].…”

“…The clinical drug that is commonly used for ischemic heart disease is sufentanil, a lipophilic opioid. It has been well reported that sufentanil treatment is able to protect the rat myocardium from I/R injury [7]. In a rabbit model of myocardial I/R, intrathecal sufentanil exhibited a cardioprotective effect [8].…”

Sufentanil alleviates cerebral ischemia-reperfusion injury by inhibiting inflammation and protecting the blood-brain barrier in rats

“… 8 In addition, SUF has also been found to alleviate myocardial ischemia-reperfusion injury by activating the ERK1/2 signaling pathway or miR-125a/DRAM2 axis. 10 , 11 A clinical study also shows that SUF can alleviate ischemia-reperfusion injury in patients with coronary heart disease. 12 Therefore, we speculated that SUF may have a therapeutic effect on ischemia-reperfusion disease.…”