【Animal modeling】-Based on autophagy to investigate the effect of fentanyl combined with propofol on cardiac ischemia-reperfusion injury in rats

  Objective To investigate the effect of fentanyl combined with propofol on cardiac ischemia-reperfusion injury in rats based on autophagy.

  Methods Thirty healthy male SPF SD rats were randomly divided into 5 groups: sham operation group, model group, fentanyl treatment group, propofol treatment group and fentanyl + propofol treatment group. Except for the sham-operated group, the myocardial ischemia-reperfusion injury model was established in the rest of the rats. The fentanyl treatment group, the propofol treatment group and the fentanyl + propofol treatment group were treated with 20 μg/kg before modeling. Fentanyl, 50 mg/kg propofol, and 20 μg/kg fentanyl combined with 50 mg/kg propofol pretreatment. The rats were sacrificed 30 min after the experiment, and the heart tissue was taken for follow-up detection. The pathological damage of rat heart tissue was observed by HE and TUNEL staining, the myocardial infarction area was observed by TTC staining, the formation of myocardial autophagy vacuoles was observed by electron microscope, and the expressions of autophagy-related proteins Beclin1, ATG5 and LC3B were detected by Western blot.

  Results Compared with the sham-operated group, the myocardial pathological changes of the rats in the model group were severely damaged, the apoptosis of cardiac cells and the percentage of infarct area increased, the mitochondria of myocardial cells swelled and the expression of autophagy-related proteins Beclin1, ATG5 and LC3B-II increased; Compared with the model group, pretreatment with 20 μg/kg fentanyl, 50 mg/kg propofol and 20 μg/kg fentanyl combined with 50 mg/kg propofol significantly reduced myocardial pathological damage in I/R rats , decreased cardiac cell apoptosis and infarct area percentage, reduced the degree of mitochondrial swelling in cardiomyocytes and decreased the expression of autophagy-related proteins Beclin1, ATG5 and LC3B-II, 20 μg/kg fentanyl combined with 50 mg/kg propionate Poofol pretreatment performed the best among them, while there was no significant difference between fentanyl and propofol.

  Conclusion Both fentanyl and propofol can inhibit myocardial cell autophagy and mitochondrial swelling, and at the same time reduce myocardial I/R injury, 20 μg/kg fentanyl and 50 mg/kg propofol can treat myocardial I/R injury. There was no significant difference in effect, and in addition, the combined use of fentanyl and propofol had a synergistic effect on myocardial I/R injury.