| Objective:To investigate the effects of phosphatidyli-nositol 3-kinase/serine-threonine kinase/endothelial nitric oxide synthase?PI3K-Akt-eNOS?signaling pathway in the treatment of isolated rat car-diac ischemia after hydromophine treatment reperfusion injury in the role of myocardial ischemia and reperfusion protection to provide theoretical support.Methods:Fifty healthy male SD rats weighing 250-320g were randomly divided into 5 groups?n=10?:?1?Control group?group C?:Balanced perfusion 120min after no other treatment;?2?Ischemia reper-fusion group?group I/R?:After 30 min of equilibration,ischemia was performed for 30 min and reperfused for 60 min.;?3?Hydromorphone af-tertreatment group?group H?:The rats were perfused with K-H solution containing 0.3?mol/L hydromorphone for 10 min before ischemia,30min before ischemia and 50 min before perfusion;?4?Hydromorphone post-treatment+PI3K inhibitor group?group HL?:The rats were per-fused with K-H solution containing 0.3?mol/L hydromorphone and 15?mol/L LY294002 for 10 min before ischemia,30 min before ischemia and 50 min before perfusion.;?5?PI3K inhibitor?group L?:The rats were perfused with K-H solution containing 15?mol/L LY294002 for 10 min before ischemia,30 min before ischemia and 50 min before perfu-sion.Observe the indicator:?1?Cardiac function was monitored in real time during perfusion,including heart rate?HR?,left ventricular systolic pressure?LVSP?and left ventricular end-diastolic pressure?LVEDP?,maximum rate of left ventricular pressure rise and maximum rate of de-cline.Cardiac function was adjusted by controlling the flow rate of KH fluid and the heart rate was recorded at the end of 30 min?T0?,the 10 min?T1?,30 min?T2?and 60 min?T3??HR?,left ventricular pressure?LVDP?and left ventricular pressure(±dp/dtmax)were calculated.The maximal increase of RPP and left ventricular pressure and the recovery of the rate of decrease were calculated.?2?The heart was taken at T3 and the content of NO in each group was measured by nitrocellulose.The area of myo-cardial infarction?AN/ARR?was determined by TTC staining.?3?Western blot was used to take the heart at T3 and GAPDH was used as an internal control to measure the protein expression of Akt,p-Akt,eNOS and p-eNOS in left ventricular myocardium.Results:Compared with group C,RPP decreased at T2 and T3 in the other four groups,and the re-covery of left ventricular pressure and descending rate decreased,the area of myocardial infarction decreased,the content of NO in myocardium decreased?P<0.05?The protein expression of p-Akt/Akt and p-eNOS/eNOS in myocardium of group R increased?P<0.05?.Compared with the group I/R,the RPP of the heart value and the recovery of the left ventricular rate increased significantly at T2 and T3 in the group H,while the NO content in the myocardial tissue increased?139.31±10.17??mol/L and heart?37.5±3.41?%,and the expressions of p-Akt/Akt?0.67±0.12?and p-eNOS/eNOS?0.71±0.15?in myocardium increased with the increase of infarct size?P<0.05?;Compared with H group,the RPP value decreased,the left ventricular pressure increased and the descend-ing rate recovered,the content of NO decreased?125.89±15.10??mol/L in HL group,The expression of p-Akt/Akt and p-eNOS/eNOS in myocardium were?0.53±0.14?and?0.62±0.16?respectively,the myo-cardial infarct size increased by 43.5±5.62%,the difference was statisti-cally significant?P<0.05?;Compared with HL group,the RPP value de-creased,the left ventricular pressure increased and the recovery rate de-creased,the content of NO in myocardial tissue decreased,the myocardial infarct size increased,The expression of p-Akt/Akt,p-eNOS/eNOS in myocardium decreased,and the differences among the groups were sta-tistically significant?P<0.05?.Conclusions:Hydromorphine can reduce the myocardial ischemia-reperfusion injury in rats may be related to the activation of P13K-Akt-eNOS signaling pathway,increased endogenous NO release. |
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