Effects Of Sufentanil Postconditioning On The Expression Of Caspase-3 Of Myocardial Ischemia-reperfusion Of Dogs And The Roles Of JAK2-STAT3

Objective To observe the effect of sufentanil postconditioning on myocardialapoptosis and the expression of caspase-3 and p-STAT3 in ischemia-reperfusioninjury of dogs, and preliminary discussion on whether its mechanism was concernedwith JAK2-STAT3 pathways.Methods Twenty-four healthy dogs, weight 10-15kg, were randomly divided intofour groups (n=6):①the control group (S group)：left anterior descending coronaryartery were stringed without ligating;②ischemia-reperfusion group (I/R group):ligation of left anterior descending coronary artery. After 30 min, blood flow wasrestored and lasted for 120 min;③sufentanil postconditioning group (PO group):intravenous injecting sufentanil (0.6μg/kg) 5 mins before reperfusion, others weretreated in the same way of IR group;④sufentanil postconditioning+ tyrosine kinaseinhibitor AG490 group (AGgroup): intravenous injecting AG490 (1mg/kg) 5 minsbefore sufentanil, others were treated in the same way of PO group. At the end of 120min of reperfusion, the myocardial specimens were removed and were put intoformaldehyde. The expressions of caspase-3, p-STAT3 and AI were examinedrespectively by immunohistochemical method and Terminal-deoxynucleoitidylTransferase Mediated Nick End Labeling method, hematoxylin-eosin staining toobserve the pathological changes of myocardium.Results1. Cell apoptosis index (AI):Compared with S group, the AI of I/R group ,PO group and AG group wereincreased (P＜0.05); Compared with I/R group, the AI of PO group and AG groupwere reduced (P＜0.05); Compared with PO group, the AI of AG group wereincreased (P＜0.05).2. Content of caspase-3 and p-STAT3:Compared with S group, the caspase-3 of I/R group ,PO group and AG groupwere increased (P＜0.05); Compared with I/R group, the caspase-3 of PO group andAG group were reduced (P＜0.05); Compared with PO group, the caspase-3 of AGgroup were increased (P＜0.05). Compared with S group, the p-STAT3 of I/R group ,PO group and AG groupwere reduced (P＜0.05); Compared with I/R group, the p-STAT3 of PO group wereincreased (P＜0.05); Compared with PO group, the p-STAT3 of AG group werereduced (P＜0.05).3.Pathological observation:Compared with S group, myocardial cell’s degeneration and the morphologicalchanges of cardiac muscle cell’s ultrastructure were significantly damaged in I/Rgroup, PO group and AG group, however, the changes of AG group were moreobviously than PO group.Conclusion1. Sufentanil postconditioning can reduce cell apoptosis, prove that sufentanilpostconditioning can protect myocardial;2. The roles of sufentanil postconditioning on myocardium protectionmechanism were ralatied with JAK2-STAT3 pathway , it maybe through increasingthe expression of p- STAT3, reducing the expression of caspase-3 to reduce the injuryof myocardium cell;3. Maybe there were exist a self-protection mechanism in myocardial cellapoptosis, and and the relationship between JAK2-STAT3 pathways and others werenot clear, pending further study;4. If there were a delayed protection ,as well as the specific mechanism deservedfurther study.