| Objective Sufentanil, a narcotics analgesics, is widely used in clinical anesthesia.Studies on it had found that sufentanil postconditioning can attenuate myocardialischemic reperfusion injury. It is known that diabetes mellitus is a major risk factor forcardiovascular disease and that diabetic is independent risk factor of myocardialinfarction. Studies showed that diabetes abrogates the ability for pharmacologicalagents to reduce myocardium infarct size by altering GSK-3β phosphorylationexpression. The purpose of this study was to investigate whether GSK-3β signalingpathway involved the influence of diabetes mellitus on the protective effects ofsufentanil postconditioning on ischemic-reperfused myocardium of rat.Methods Healthy adult male SD rats, weighing250-300g,which diabetes mellitusmodel was successfully established by intraperitoneal streptozotocin50mg/kg, and theischemia reperfuion injury model were elicited by30min occlusion of LAD followedby120min reperfusion. Forty-eight male SD rats (24with diabetes and24withoutdiabetes) were randomly divided into4groups (n=6each) respectively: sham operationgroup (group S): rats were received no occlusion or reperfusion; ischemia-repefusiongroup (group IR)：rats were subjected to30min ischemia and120min reperfusion,fora negative control group,0.9%normal saline1ml was infused at5min beforereperfusion.; sufentanil postconditioning group (group SP): rats were received postconditioning with sufentanil1.0ug/kg diluted with0.9%normal saline1ml at5min before reperfusion. SB216763group (group SB): rats were received GSK-3βinhibitor SB2167630.6mg/kg diluted with final concentration of0.01%DMSO at5min before reperfusion. MAP, HR and RPP (HR×SBP) were recorded before ischemia,30min of ischemia and120min of reperfusion. Arterial blood samples were collectedat120min of reperfusion for measurement of cTnI concentration. The animals werethen sacrificed for determination of total areas of LV+RV、IS、AAR and IS/AAR. Tomeasure the myocardial levels of p-GSK-3β、GSK-3β protein expression, myocardialtissue samples from group NDM-IR、NDM-SP、NDM-SB、DM-SB、DM-SP andDM-IR (n=4each) were collected five minutes following reperfusion. Expression ofp-GSK-3β、GSK-3β were assessed by Western blotting.Results Characteristic of rats: After administration of a single dose ofstreptozotocin, diabetic rats had significantly higher levels of plasma glucose thanthe non-diabetic rats (p <0.05). Heart weight and body weight were lower in thediabetic group than in the non-diabetic group (p <0.05). Hemodynamic parameters:The MAP、 RPP significantly decreased after ischemia-reperfusion compared tobaseline in all groups except NDM-S group, DM-S group.Baseline HR was lower inDM-S group than in NDM-S group. Compared to their corresponding S group, allgroups also had a lower MAP、RPP (p <0.05). Myocardial infarct size and cTnI:Compared to NDM-S group, the LV+RV was significant less in DM-S group (p <0.05). Compared to their corresponding S group, all groups had a higher plasmaconcentrations of cTnI. Compared with NDM-IR group,the IS、IS/ARR and plasmaconcentrations of cTnI significantly decreased in NDM-SP group and NDM-SB group(p <0.05); The IS、IS/ARR and plasma concentrations of cTnI were significant less inDM-SB group than in DM-IR group(p <0.05). However, there were no significantdifferences in these variables between the DM-SP group and DM-IR group(p>0.05). Compared with NDM-SP group, the IS、IS/ARR and plasma concentrations of cTnIsignificantly increased in DM-SP group(p <0.05). GSK-3β western blot analysis:The total GSK-3β levels did not vary between study groups(p>0.05). NDM-SP groupand NDM-SB group had higher p-GSK-3β protein levels（p-GSK-3β/GSK-3β）,compared with the NDM-IR group. p-GSK-3β protein levels was higher in DM-SBgroup than in DM-IR group (p <0.05). However, no significant difference was foundbetween DM-IR and DM-SP group. Compared with NDM-SP group, p-GSK-3βprotein levels significantly increased in DM-SP group(p <0.05).Conclusions Sufentanil postconditioning can protect myocardium against I/R injuryin nondiabetic rat heart，however this effect can be abolished by diabetes mellitus,which is associated with the activation of GSK-3β. Our results also suggest thatGSK-3β inhibitor SB216763can protect both diabetic and nondiabetic hearts againstI/R injury. |
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