Involvement of p38 mitogen-activated protein kinase in myocardial ischemia/reperfusion injury through down-regulating sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2α in rats

Objective To investigate the effects of p38 mitogen-activated protein kinase (p38MAPK)- sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2α (SERCA2α) signaling pathway on myocardial ischemia/reperfusion injury (I/RI) in rats. Methods Forty-five male SD rats (250 ‒ 300 g in weight) were divided into three groups according to the random number table method (n=15): group A, group B and group C. Group A was used to measure the size of myocardial infarct. Group B was adopted to determine the levels of p38MAPK and SERCA2α protein in myocardial tissues. Group C was used to examine the expression of SERCA2α mRNA in myocardial tissues. Then, rats in groups A, B and C were divided into three groups by the random number table method respectively (n=5): a sham-operated group (group sham), an ischemia/reperfusion (I/R) group (group I/R), and an ischemia/reperfusion+SB203580 group (group I/R+S). Group I/R+S was intraperitoneally injected with p38MAPK inhibitor SB203580 (2 mg/kg) 1 h before surgery, while the other two groups were injected with an equal volume of normal saline 1 h before surgery. A model of myocardial I/RI was established in rats through ligation of the left anterior descending (LAD) coronary artery over 30 min before reperfusion for 10 min. After the end of reperfusion, blood gas analysis was performed to monitor the internal environment of rats. Western blot was used to detect the expression of phospho-p38MAPK (p-p38MAPK) and SERCA2α protein in myocardial tissues. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of SERCA2α mRNA in myocardial tissues. Myocardial ischemia and infarct size were measured by Evans blue and 2, 3, 5-triphenyl tetrazolium chloride (TTC) double staining. Results There was no statistical difference in the results of gas blood analysis among the three groups (P>0.05). Compared with group sham, groups I/R and I/R+S presented remarkable increases in myocardial infarct size and the levels of p-p38MAPK protein (P<0.05), and marked decreases in the levels of SERCA2α protein and mRNA (P<0.05). Compared with group I/R, group I/R+S produced remarkably decreased myocardial infarct size and p-p38MAPK protein levels (P<0.05), and marked increased amounts of SERCA2α protein and mRNA (P<0.05). Conclusions p38MAPK may be involved in myocardial I/RI in rats through mediating SERCA2α. Key words: Myocardial reperfusion injury; p38 mitogen-activated protein kinase; Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2α