Abstract Objective:To investigate the effect on type Ⅱ diabetes mellitus of the myocardial ischemia-reperfusioninjury by sufentanil postconditioning in rats and its relation with PI3K-Akt. Method:24 healthy male SD rats weighingfrom 180-200 g were randomly divided into 4 groups by random number mber table method( n=6): nondiabetic mellitus shamoperation group( NDM-S group), nondiabetic mellitus ischemia-reperfusion group( NDM-I/R group), nondiabetic
mellitus sufentanil postconditioning group( NDM-SP group) and nondiabetic mellitus sufentanil postconditioning +wortmannin( PI3K-inhibitor) group( NDM-SP+W group). More healthy male SD rats were made into T2DM model(Glucose ≥ 16.7 mmol/L) by the following method: feeding them with high-sugar and high-fat diet for 6 weeks to induceinsulin resistance and giving intraperitoneal injection of streptozotocin with the dosage of 35 mg/kg. Selected 24 rats that
were successfully molded and keeping on feeding them with high-sugar and high-fat diet for 2 more weeks. to They weredivided into 4 groups( n=6) by random number table method: diabetic mellitus sham operation group( DM-S group),diabetic mellitus ischemia-reperfusion group( DM-I/R group), diabetic mellitus sufentanil postconditioning group( DMSPgroup) and diabetic mellitus sufentanil postconditioning + wortmannin group( DM-SP+W group). The model of ratswith myocardium ischemic reperfusion was made by the following method: carrying out threading or ligation below theleft anterior descending branch of coronary artery, blocking for 30 min and giving reperfusion for 120 min. But threadingcan only be carried out for the sham operation groups. After 5 min’s stabilization of the ischemia-reperfusion groups,should be blocked for 30min and reperfused for 120 min. For sufentanil postconditioning groups, sublingual IV injectionof 1.0 μg/kg sufentanil was given 5 min before the reperfusion, while sublingual IV injection of 15 μg/kg wortmanninand 1.0 μg/kg sufentanil were given for the sufentanil postconditioning + wortmannin groups. Blood sample was takenafter 120 min’s reperfusion to check the cTnI level. Myocardial tissues were collected after rats’ death to check the AIof cardiomyocytes by TUNEL method and the Akt, p-Akt level of myocardial tissues by Western blot method.Result:
Compared I/R, SP and SP+W groups with S group of both NDM and DM rats, the cTnI level in plasma of the former groupswas obviously elevated, as well as increased AI and p-Akt level(P<0.05). Sufentanil postconditioning could obviouslyreduce the MI/RI of NDM group, which could lower the cTnI and AI level and increase the p-Akt level(P<0.05), but ithad no obvious effect on the MI/RI of DM group. The cTnI level in plasma and AI of the NDM-SP group were obviously
lower than the DM-SP group, while the p-Akt level of former group is higher than the latter.Conclusion:Sufentanilpostconditioning has no protective effect on type Ⅱ diabetes mellitus against myocardial ischemia-reperfusion injury in ratsand PI3K-Akt pathway is not involved in this process.
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