Dexmedetomidine alleviatesmyocardial ischemia-reperfusion injury in rat models

Objective To investigate the relationship between the protective mechanism of dexmedetomidine (Dex) against myocardial ischemia-reperfusion(I/R) injury and cuproptosis. Methods The Langendorff models were constructed using SD rats(I/R group), which were divided into 4 groups according to different interventions during reperfusion as: sham group, I/R group, Dex group and Dex+ES-Cu group. The left ventricular peak pressure(LVSP)of the rats in the above four groups were continuously monitored in the immediate pre-ischemic period(T0), 30 min of reperfusion(T1), 60 min reperfusion(T2), 90 min reperfusion(T3),2 h of reperfusion(T4). Left ventricular end-diastolic pressure(LVEDP), heart rate (HR), maximum rate of rise of left ventricular pressure (+dp/dtmax) and maximum rate of drop. Subsequently, the extent of myocardial infarction was shown by1% triphenyltetrazoliumchloride (TTC) staining, and the degree of myocardial fibrosis was assessed by Sirius red staining; Myocardial enzyme profiles, oxidative stress and inflammation indexes were detected by ELISA; Copper ions were detected by copper ion detection kit in myocardial tissues; ATF3, SPI1 and FDX1 protein level expression was detected by Western blot. Results Compared with the sham-operated group, the extent of myocardial infarction and fibrosis increased in the I/R group(P＜0.05), the level of serum MDA, IL-6, IL-1β, and TNF-α was elevated(P＜0.05), and the activity of SOD and GSH-Px decreased(P＜0.05). The Dex group significantly alleviated the above changes in the I/R group, and compared with the Dex group, in the Dex+ES-Cu group myocardial tissue copper ion content at the end of perfusion was increased(P＜0.05). Both ATF3 and SPI1 protein were increased and FDX1 protein was decreased(P＜0.05). Conclusions Dex can regulate copper metabolism and improve myocardial ischemia-reperfusion injury(MI/RI) resulted from oxidative stress and inflammation in rat model.