ABSTRACT
Objectives:To explore the possible mechanisms of ischemic postconditioning on alleviating myocardial ischemia-reperfusion injury, focusing on the inflammatory-thrombus related mechanisms. Methods:Rats were randomly divided into six groups (n=10 each):sham group, ischemia-reperfusion injury group, postconditioning group, SB203580 group, anisomycin+postconditioning (Ani+postconditioning) group and anisomycin (Ani) group. After establising the model of myocardial ischemia reperfusion in rats, the levels of myocardial injury markers troponin I (TnI) and creatine kinase isoenzyme (CK-MB), level of leukocyte-platelet aggregation (PLA) were detected by flow cytometry at different time points, myocardial infarction area was measured by using TTC staining and the level of phosphorylation of p38 MAPK (P-p38 MAPK) was determined by Western blot. Results:Compared with the I/R group, the levels of CK-MB, TnI, the infarct size and the expression of PLA at 60 min and 3 h reperfusion were significantly reduced in the postconditioning group and SB203580 group (P＜0.05). Compared with the postconditioning group, the levels of above parameters were significantly higher in the SB203580 group, Ani+postconditioning group and Ani group (P＜0.05). Compared with the I/R group, the expression of P-p38 MAPK in the postconditioning group, SB203580 group, Ani+postconditioning group was significantly reduced (P＜0.05), while it was significantly upregulated in the Ani group (P＜0.05). Furthermore, compared with the postconditioning group, the expression of P-p38 MAPK in the Ani+postconditioning group and Ani group was significantly upregulated (P＜0.05). SB203580 group presented the similar protection effect as the postconditioning group. Cardioprotective effects of postconditioning was partially reduced in the Ani+postconditioning group. Conclusions:Ischemia postconditioning can reduce the expression of PLA during reperfusion by inhibiting the phosphorylation of p38MAPK, thereby attenuating myocardial ischemia-reperfusion injury.
ABSTRACT
Objective To observe the effect of postconditioning (PostC) on the expression of platelet-leukocyte aggregation (PLA) during the process of myocardial ischemia and reperfusion in rats, and to explore the mechanisms of ischemic postconditioning (PostC) alleviating myocardial ischemia-reperfusion injury (MIRI). Methods Sixty rats were randomly divided into six groups:sham,reperfusion injury(I/R),postconditioning(PostC),SP600125(inhibition of c-Jun N-terminal kinase,I-JNK),anisomycin and postconditioning(Ani+PostC)and anisomycin(Ani)groups.After constructing the model of myocardial ischemia reperfusion in rats,the levels of myocardial injury markers were detected by using the CK-MB kits and TnI kits. The levels of PLA at different time points were detected by using flow cytometry.The myocardial infarction area were measured by using 2.3.5-Triphenyte-trazoliumchloride(TTC)staining,and the level of phosphorylation of JNK(P-JNK) was determined by using Western blot method. Results (1) The levels of CK-MB, TnI and the infarct size were significantly higher in the I/R group than those in the Sham group(P<0.05).The levels of CK-MB,TnI and the infarct size were significantly lower in the PostC group and I-JNK group than those in the I/R group(P<0.05).Compared with the PostC group,the levels of CK-MB,TnI and the infarct size were significantly higher in the Ani+PostC group and Ani group(P<0.05).(2)Compared with the Sham group,the expression levels of PLA significantly increased in the I/R group at different time points after ischemia (P<0.05). At different time points of MIRI, the expressions of PLA increased gradually in I/R group, Ani+PostC group and Ani group (P<0.05). At the time point of reperfusion for 60 minutes and reperfusion for 3 hours,the expressions of PLA were significantly lower in the PostC group and I-JNK group compared with those of I/R group (P<0.05).Compared with the PostC group,the expressions of PLA were significantly higher in the Ani+PostC group and Ani group (P<0.05). (3) Compared with the Sham group, the expression levels of P-JNK were significantly higher in the I/R group(P<0.05).PostC and I-JNK inhibited the production of P-JNK(P<0.05),while Ani promoted the increase of P-JNK (P<0.05).Compared with the PostC group,the expression levels of P-JNK were significantly higher in the Ani+PostC group and Ani group (P<0.05). Conclusion PostC can reduce the expression of PLA during reperfusion by inhibiting the phosphorylation of JNK,thereby reducing myocardial ischemia-reperfusion injury.