[Effect of ischemic postconditioning on activation of p38 mitogen activated protein kinase and cardiac myocyte apoptosis in rats].

Objective: To explore the change of phospho-p38 (P-p38) mitogen activated protein kinase(MAPK) and its influence on myocardial apoptosis in reperfusion injury in postconditioning.

Methods: Totally 60 rats were equally and randomly divided into six groups: Sham group,reperfusion injury (R/I) group, postconditioning (Post) group, SB203580 (I_p38) group, anisomycin plus postconditioning (Ani+post) group,and anisomycin (Ani) group. After the model of acute myocardial infarction was established,placebo solution (DMSO), SB203580 (1 mg/kg), or anisomycin (2 mg/kg) was injected through jugular vein 5 minutes before reperfusion. Six hours later, 3 rats in each group were executed and the hearts were separated to measure the signaling molecules including phospho-p38,tumor necrosis factor-alpha (TNF-α), Caspase-8, Bcl-2/Bax, and cytochrome-c (Cyt-c). Twenty-four hours later,the hemodynamic data were measured in the remaining rats,and then blood was collected to determine the serum markers of cardiac damage. After that,hearts were separated to measure the infarction area and apoptosis.

Results: Six hours after reperfusion,the expressions of P-p38 in Post and I_p38 group were significantly lower than those in R/I group (P<0.05), significantly higher in Ani+post and Ani group than in Post group (P<0.05), and significantly lower in Ani+post group than in R/I group (P<0.05). The expressions of TNF-α and Caspase-8 were significantly lower in Post and I_p38 group than in R/I group (P<<.05) and significantly higher in Ani+post and Ani group than in Post group (P<0.05). The expression of TNF-α was significantly lower in Ani+post group than in R/I group (P<0.05). The expression of Bcl-2 was significantly higher in Post and I_p38 groups than in R/I group (P<0.05) and significantly lower in Ani+post and Ani groups than in Post group (P<0.05). The expression of Bax was significantly lower in Post and I_p38 groups than in R/I group (P<0.05) and were significantly higher in Ani+post and Ani group than in Post group (P<0.05). The expression of Cyt-c after the removal of the cytoplasm mitochondria was significantly lower in Post and I_p38 group than in R/I group (P<0.05) and was significantly higher in Ani+post and Ani group than in Post group (P<0.05). Twenty-four hours after reperfusion,the values of rate-pressure product and ± delta pressure/delta time max were significantly lower in R/I group than in Post and I_p38 groups (P<0.05) and was significantly higher in Post group than in Ani+post and Ani group (P<0.05). The apoptotic index (AI) was significantly lower in Post and I_p38 groups than in R/I group (P<0.05) and was significantly higher in Ani+post and Ani groups than in Post group (P<0.05). The values of creatine kinase and creatine kinase-MB were significantly lower in Post,Ani+post, and I_p38 groups than in R/I group (P<0.05) and were significantly higher in Ani+post and Ani group than in Post group (P<0.05). The area of necrosis/area at risk ratio was significantly lower in Post and I_p38 groups than in R/I group (P<0.05) and was significantly higher in Ani+post and Ani groups than in Post group (P<0.05).

Conclusion: Postconditioning can inhibit the phosphorylation of p38 MAPK,through which it can attenuate cardiac myocyte apoptosis by both extrinsic and mitochondria pathways.