The Effect Of Nalbuphine Pretreatment On Myocardial Injury Induced By Ischemia Reperfusion In Diabetic Rats

Objective:The purpose of this experiment was to observe the effect of opioid receptor-agonist nalbuphine on hemodynamics and markers of myocardial injury in diabetic rats after myocardial ischemia and reperfusion.The in-depth study of the effect of naproxen agonizing κ receptor and partially antagonizing μ receptors on cardiomyocytes provides a reference for the clinical treatment of diabetic ischemic reperfusion injury(IRI).Method:36 healthy Sqrague-Dawley rats weighing 150-170 g and 4-6 weeks old were selected.Randomly divide into diabetic group(DM)and non-diabetic group(NDM).After 1 week of adaptive feeding,the NDM rats were randomly divided into 3 groups(n=6): non-diabetic sham operation group(NDM-S group),non-diabetic and myocardial ischemia-reperfusion group(NDM-I/R group)Non-diabetic and myocardial ischemia-reperfusion and nalbuphine pretreatment group(NDM-NP group).Rats in DM group were fed with high-fat diet for 4 weeks and fasted for 12 hours.Rats with type 2 diabetes were duplicated by intraperitoneal injection of 1% streptozotocin sodium citrate buffer(STZ,35 mg/kg).One week after the injection,blood glucose levels were continuously monitored,and blood was drawn from the tail vein of rats to determine the random blood glucose(≥16.7 mmol/L)with symptoms such as polydipsia,polyphagia and polyuria.Eighteen successful rats were selected and continued to be fed with high-fat for 4 weeks.They were randomly divided into 3 groups(n=6): diabetic sham operation group(DM-S group),diabetes mellitus and myocardial ischemia-reperfusion group(DM-I/R group),diabetes and myocardial ischemia-reperfusion and nalbuphine pretreatment group(DM-NP group).The myocardial ischemic reperfusion model was established by threading or ligation of the left anterior descending coronary artery for 30 min and reperfusion for 120 min.During the experiment,heart rate(HR),mean arterial pressure(MAP),and systolic blood pressure(SBP)values were recorded immediately before ischemia(T1),30 min(T2)of ischemia,and 120 min(T3)of reperfusion.And calculate RPP.At the end of 2 hours after reperfusion,blood samples were taken to determine the content of cTn I in the injured myocardium.Myocardial infarct size was assessed by TTC staining.Result:1.The weight of the DM group was lower than that of the NDM group(n=18,P<0.0001),and the blood glucose level was significantly higher(n=18,P<0.0001).2.Pretreatment with nalbuphine increased MAP(n=6,P<0.05)in myocardial ischemic reperfusion in NDM group,but there was no significant effect of MAP on myocardial ischemia-reperfusion in DM group.3.Pretreatment with nalbuphine increased HR,SBP and RPP during myocardial ischemia and reperfusion in NDM group(n=6,P<0.05),but no significant effect on HR,SBP and RPP during reperfusion in DM group..4.The concentration of cTn I in NDM-NP group was lower than that in NDM-I/R group(n=6,P<0.0001).The concentration of cTn I in DM-NP group was not significantly different from that in DM-I/R group(P>0.05).5.The infarct size of NDM-NP group was significantly smaller than that of NDM-I/R group(n=6,P<0.0001).The infarct size of DM-NP group was smaller than that of DM-I/R group(n=6,P<0.0001).The infarct size of NDM-NP group was smaller than that of DM-NP group(n=6,P<0.05).Conclunsion:1.Hemodynamic parameters(MAP,HR,SBP,and RPP)decreased,plasma cTnI concentrations increased,and myocardial infarction like pathological changes were observed,all rats in the changes of myocardial ischemia reperfusion index.2.Relatively elevated hemodynamic parameters(MAP,HR,SBP,and RPP),decreased plasma cTnI concentration,and reduced myocardial infarct size were all changes in myocardial ischemia and reperfusion in NDM rats pretreated with nalbuphine;However,the effect of each index was small or had no significant effect on myocardial ischemia and reperfusion in DM rats.3.Pretreatment with nalbuphine relieves myocardial ischemia-reperfusion injury in rats.Diabetes mellitus,as an influencing factor,is highly likely to counteract the effect of nalbuphine preconditioning on myocardial ischemia-reperfusion injury in rats.