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Objective: To investigate the protective effect of 11,12-EET(11,12-epoxyeicosatrienoic acid)on myocardium of immature rabbit hearts from ischemic reperfusion injury. Methods: 16 isolated immature rabbit hearts were performed to ischemic reperfusion model in a Langendorff perfusion apparatus and randomlyassigned to on two groups. Control group, the hearts were arrested with St.Thomas No.2 solution and stored in the same solution (n=8). EET group, the hearts were arrested with St.Thomas No.2 plus 11,12-EET solution and stored in the same solution (n=8). These isolated rabbit hearts were stored for 8 hours at 4℃ hypothermia , and underwent 30 minutes of reperfusion (37℃). We measured the preischemia and postreperfusion indexes of left ventricle developed pressure (LVDP), left ventricle end-diastolic pressure (LVEDP), ?dp/pt_ max , myocardial water content (MWC), coronary blood effluent (CBE) and arrhythmia score (AS). The myocardial ultrastructure and value of creatine kinase (CK) and lactic dehydrogenase (LDH) were also observed. Results: (1) After 30 minutes reperfusion, the indexes of CK, LDH, CBE, AS,and the recovery rate of heart function were significantly better in EET group compared with controls. At the same time, no ultrastructural changes were found in the EET group while the capillary endothelial base membrane edema and mitochondrion edema was observed in the control group. (2) In EET group, compared with preischemia, there were no significantly changes of myocardial function at the end of 30-minutes reperfusion. Conclusion: These data suggest that 11,12-EET add to the St.Thomas No.2 solution could offer more little myocardial injury and little arrhythmia and provide better preservation of the isolated immature hearts.
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AIM: To study apoptosis and bcl-2 mRNA gene expression of cardiomyocytes in donor hearts of immature rabbits underwent prolonged protection by 11, 12-epoxyeicosatrienoic acid (11, 12-EET), and further probe into the possible mechanisms. METHODS: 24 isolated immature rabbit hearts were performed to the model in a Langendorff perfusion apparatus and randomly assigned to normal control group,ST control group and EET group. The isolated rabbit hearts in ST control group and EET group were stored for 24 hours with 4 ℃ hypothermia, and underwent 30 minutes of reperfusion (37 ℃). TUNEL and in situ hybridization (ISH) methods were applied in the present study and apoptotic cells and bcl-2 mRNA gene expression were observed. RESULTS: The numbers of apoptotic cardiomyocytes in ST group and EET group were higher than that in normal control group, and the numbers of apoptotic cardiomyocytes were significantly decreased in EET group and bcl-2 mRNA positive expression were higher than that in ST control group, respectively. CONCLUSIONS: There were apoptosis during the prolonged protection of donor heart in our study, and we proved that: ①11,12-EET could decrease cardiomyocyte apoptosis significantly. ②Up-regulation of the bcl-2 mRNA expression in cardiomyocytes may be one of the mechanism responsible for inhibition of cardiomyocyte apoptosis by 11, 12-EET.
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AIM: In order to study the relationship between the ERK and p38 MAPK activation and the protection of 11, 12-epoxyeicosatrienoic acid (11, 12-EET) and ischemia preconditioning (IP), the effects of 11, 12-EET and ischemic preconditioning on phosphorylated ERK and p38 MAPK during ischemia and reperfusion in rat myocardium were examined. METHODS: The rat heart was subjected to ischemia for 5 min by ligating the left anterior descending coronary artery followed by reperfusion for 5 min (two times) to undergo ischemia preconditioning. The rats were divided into 5 groups: (1) control; (2) sham group; (3) ischemia/reperfusion (I/R) group, in which the rat heart suffered from 60 min ischemia followed by 30 min reperfusion; (4) IP plus I/R group; (5) EET plus I/R group, in which 6.28?10 -8 mol/L 11, 12-EET was injected intravenously 20 min before I/R. The heart function was examined, and phosphorylated ERK and p38 MAPK were detected by Western blot. RESULTS: At 30 min reperfusion, +dp/dt max ,-dp/dt max and LVDP decreased significantly in I/R group compared with sham group, IP plus I/R group and EET plus I/R group; Phosphorylated ERK1/2 level was higher in I/R group than sham group, but was lower in I/R group than IP plus I/R group and EET plus I/R group; Phosphorylated p38 MAPK level was lower in control, sham, IP plus I/R and EET plus I/R group than I/R group. CONCLUSION: 11,12-EET protects rat heart against ischemia/reperfusion injury, the mechanism may be related to activation of ERK1/2 and inhibition of p38 MAPK. [
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AIM:To study the effects of Hydrogen Peroxide(H2O2)and 11,12-epoxyeicosatrienoic acid(11,12-EET)on EDHF-mediated relaxation in the rat basilar arteries.METHODS: The relaxant effects of acetylcholine(ACh),H2O2,11,12-EET,and catalase(CAT) on rat arteria basilaris in vitro were detected by vasomotoricity experiment in vitro.RESULTS: In the rat basilar arteries,preconstricted by 30 mmol/L KCl in vitro,ACh(10-7-10-4.5 mol/L) had the concentration-dependent relaxation effect.3?10-5 mol/L N?-nitro-L-arginine-methyl-ester(L-NAME) and 10-5 mol/L indomethacin(Indo) could partly inhibit the relaxation effect of ACh to the rat basilar arteries,but non-No/non-PGI2-mediated relaxation was still significant(P
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Aim To investigate the expression of phosphorylated JNK1/JNK2 and the protection of 11,12-EET in ischemic and reperfusion rat heart.Method The expression of JNK1/JNK2 was detected with western blot method and the changing of heart function during ischemia/reperfusion process was observed in different groups. Results The cardiac function (+dp/dt_(max)%,-dp/dt_(max)% and LVDP)of reperfusion periods(30 min) apparently decreased in ischemia/reperfusion (I/R) group contrasted with Sham group, short ischemia(SI)+I/R group and EET+I/R group,and the expression of phosphorylated JNK1/JNK2 increased in I/R group contrasted with nromal group,Sham group and EET+I/R group.Conclusion The myocardial protection of 11,12-EET ( 6.24?10~(-8) mol?L~(-1)) is able to inhibit the expression of phosphorylated JNK1/JNK2.