| Objective Sufentanil,a narcotics analgesics,is now widely used in clinicalanesthesia. It had been proved that sufentanil post conditioning can attenuatemyocardial ischemic reperfusion injury. It is known that diabetes mellitus is anindependent risk factor of myocardial infarction. Preliminary studies showed that type1diabetes mellitus can abrogates the cardial protective effect of sufentanil on rat heart,which may achieved by altering GSK-3β phosphorylation expression. Type2diabetic are the vast majority of the whole diabetic. The purpose of this study was toinvestigate the cardial protective effect of sufentanil on ischema repufersion heart oftype2diabetic models and weather GSK-3β was involved.Methods Healthy SPF male SD rats, weighing160-180g, were randomly dividedinto two groups, one for developing type-2diabetic models using high fat combinedwith STZ injection method and one for contrast with nomal feed. The ischemiareperfuion injury model was elicited by120min reperfusion follwing30min occlusionof LAD. Forty-eight rats (24with diabetes and24without diabetes) were randomlyrespectively divided into4groups (n=6each): sham operation group (group S): ratsreceived a line under LAD, but no occlusion and reperfusion; ischemia-repefusiongroup (group IR):rats were subjected to30min ischemia followed by120minreperfusion, for negative control,1ml of0.9%normal saline was infused5min beforereperfusion.; sufentanil postconditioning group (group SP): rats received sufentanil1.0 ug/kg diluted in1ml of0.9%normal saline5min before reperfusion. SB216763group (group SB): rats received specialy GSK-3β inhibitor SB2167630.6mg/kgdiluted in0.01%DMSO5min before reperfusion. HR, MAP and RPP (HR×SBP)were recorded and calculated the moment before ischemia,30min of ischemia and120min of reperfusion. Arterial blood samples were collected at120min of reperfusion formeasurement of cTnI concentration. Rats were then sacrificed and hearts were dyedfor determination of volume of LV+RV、IS、AAR and IS/AAR. Another32rats (16with diabetic,16without diabetic) were divided into8groups (n=4each) respectively.5mins after reperfusion, left ventricular tissue samples were collected to measurep-GSK-3β、GSK-3β protein expression levels.Results Characteristic of rats: After8weeks feed with high fat and a single dose ofstreptozotocin injection, rats in diabetic model groups had significantly higher plasmaglucose levels than that in normal feed groups (p <0.05). Body weights were lowerin diabetic groups than that in normal feed groups (p <0.05). Hemodynamicparameters: MAP、RPP levels significantly decreased compared to baseline afterischemia in all groups except sham group. Compared to corresponding S groups, allgroups had lower MAP、RPP (p <0.05). HR levels had no statistic changes betweendifferent time points and groups. Myocardial Infarct Size and cTnI: Compared withcorresponding S groups, all groups had myocadial infarct areas and higher plasmaconcentrations of cTnI after120min reperfusion. Compared with NDM-IR group, IS、IS/ARR and plasma concentrations of cTnI significantly decreased in NDM-SP groupand NDM-SB group (p <0.05); compared with DM-IR group, IS、IS/ARR and plasmaconcentrations of cTnI were significant lower in DM-SB group (p <0.05), but nostatistic differences in DM-SP group (p>0.05). P-GSK-3β, GSK-3β analysis: TheGSK-3β protein levels did not vary between all the groups (p>0.05). NDM-SP groupand NDM-SB group had higher p-GSK-3β protein levels（p-GSK-3β/GSK-3β）than that of NDM-IR group. DM-SB group had higher P-GSK-3β protein levels than thatin DM-IR group (p <0.05). No statistic difference was found between that in DM-IRand DM-SP group (p>0.05).Conclusions Sufentanil postconditioning can protects rat hearts from ischemiarepufersion injury, this effect can be abolished by type2diabetes mellitus, which mayaffects the actived level of GSK-3β. Inhibition of GSK-3β may provide a strategy toprotect type2diabetic hearts against I/R injury. |
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